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• trial_statuses(array)
  • 1Recruiting
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• applications(array)
  • 0(array)
    • Application(array)
      • id1209
      • user_id796
      • trial_status_id1
      • abstract_of_study<p>\n Sickle cell disease is a chronic hemolytic anemia caused by inheritance of a mutated form of hemoglobin (Hb), sickle Hb (HbS). The disease is characterized by polymerization of HbS in RBCs when in the deoxygenated state, resulting in a sickle-shaped deformation of RBCs. Sickled cells aggregate in capillaries precipitating vaso-occlusive events that generally present as acute and painful crises (VOC) resulting in tissue ischemia, infarction, and long-term tissue damage, that underlies the significant morbidity and increased mortality associated with this disease. Red blood cells in SCD patients tend to be fragile due to sickling and other factors, and the mechanical trauma of circulation causes hemolysis and chronic anemia. Sickle cell disease is the most common inherited hemolytic anemia, affecting approximately 100,000 individuals in the United States (US) (CDC 2020), approximately 35,000 to 164,000 individuals in Europe, and millions more worldwide (Hassell, 2010; Lobitz et al, 2018). In Kenya, Ministry of Heath estimates that at least 6000 children are born annually with SCD. The paediatric to adult ratio stands at 3:1 and Sickle Cell disease has been found to be more prevalent in areas with high prevalence of Malaria in Kenya (Williams et al., 2005). Kombewa lies in the area with high prevalence of Malaria. Therapeutic treatment of SCD remains inadequate. Potentially curative therapies, such as bone marrow transplant or gene therapies are invasive and such high-risk procedures are available to only a limited number of patients. For most patients, treatment involves supportive care for management of vaso-occlusive crisis (VOC) or the use of hydroxyurea (HU), to stimulate production of fetal Hb (HbF) and reduce Hb polymerization. However, the myelosuppressive and teratogen effects of HU limit its effectiveness. More recently other therapies have been approved; L-Glutamine to reduce the acute complications of SCD, Volexotor, indicated to reduce hemolysis and improve hemoglobin levels, and Crizanlizumab to reduce the incidence of VOCs. None of these therapies results in both improvement of anemia and a reduction in the frequency of VOCs. Additional therapies that target the underlying physiology are needed. Pyruvate kinase R (PKR) is the isoform of Pyruvate kinase expressed in RBCs and its activation is proposed to directly target both sickling by reducing deoxy-HbS and Hemolysis by improving RBC membrane integrity. The study drug, Etavopivat (FT-4202) is a potent selective activator of PKR. This is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study among SCD patients, aged 12 to 65 years. The primary objective is to assess the efficacy of FT-4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb) and annualized vaso-occlusive crisis (VOC) rate. The Phase 2, is the dose determination portion and the selected dose will be assessed in Phase 3, the efficacy portion against placebo. Following a double blind period of 52 weeks, all patients may enter a 52-week open-label extension period. The study will enroll approximately 344 adult and adolescent patients with SCD, who fulfill the eligibility criteria (60 to 90 patients in the Dose Determination Group and approximately 274 patients in the Efficacy Continuation Group). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. Study activities during visits will include but not limited to a physical, vital signs, randomization, 12-Lead ECG, and various laboratory assessments at screening and as part of efficacy and safety assessments at time points as per the protocol Schedule. Patients will be evaluated for safety by collection of adverse events (AEs)/serious adverse events (SAEs), laboratory tests and vital signs. Serious adverse events will be collected from the time of signature of informed consent throughout the dosingperiod and including the follow-up period. Ethical approvals will be sought from the relevant authorities prior to study implementation. Results from the overall study will inform the potential usefulness of FT-4202 in the treatment of patients with SCD.</p>\n
      • study_title<p>\n An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)</p>\n
      • laymans_summary<p>\n Sickle cell disease (SCD) is an blood disease that causes the Red blood cells in blood to (RBCs) to change to sickle shape. Sickled cells do not flow easily through small blood vessels and may cause obstruction resulting in recurrent episodes of pain. These episodes are referred to as vaso-occlusive events (VOC). The sickled cells have a shorter life span than the non sickled cells and this results in low blood levels (anaemia). SCD affects about 100,000 patients in the United States, up to 164,000 patients in Europe, and millions more in the rest of the world. In Kenya, the Ministry of Health estimates that at least 6000 children are born with SCD every year. Sickle Cell disease patients are found in larger numbers in areas with where Malaria common than in areas where malaria is less common in Kenya (Williams et al., 2005). Kombewa lies in an area where Malaria is common. Cure for SCD can be achieved by procedures called bone marrow transplant or gene therapies, but these are not available or possible for all patients and are also expensive. For most patients treatment is mainly supportive; pain control, blood transfusions or the use of hydroxyurea (HU). Newer treatments have been developed that increase blood level or reduce frequency of VOCs but none of the treatments does both. The search for other treatmentsis on going. The study drug, Etavopivat (FT-4202) is a potent activator of a protein called Pyruvate kinase R (PKR), which is key in the process of generating energy in the body. It is that PKR activation will reduce the rate of RBC sickling and RBC destruction leading to less frequent episodes of pain(VOC) and increased blood levels. This study is designed to take place in phases among patients with SCD, aged 12 to 65 years. The phase 2 is the dose determination portion when patients will receive one of two dose levels of study drug or placebo (a placebo is a substance that looks like the study drug but has no effects on the body). The selected dose will be assessed for efficacy (effectiveness) in Phase 3, for increasing blood level and reducing episodes of VOC, over 52 weeks, when compared to a placebo (). After the 52 week follow up period the patients may enter 52 weeks period in which all patients receive the study drug. This study will enroll up to about 344 patients with SCD (60 to 90 patients in the Dose Determination Group and 274 patients in the Phase 3). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. At study pre-determined time points, the participants will undergo heath assessments; physical examinations, taking of vital signs (e.g. temperature, Blood pressure, heart rate, respiratory rate), recording heart activity using an electrocardiogram (ECG), and various laboratory assessments as part of follow up safety assessments. All the information will be recorded and then analyzed. Ethical approvals will be sought from the relevant authorities prior to study start. Results from the overall study will inform on the potential usefulness of the study drug (FT-4202) in the treatment of patients with SCD</p>\n
      • short_titlePRAISE
      • protocol_noECCT/23/01/02
      • version_no2.0
      • date_of_protocol15-10-2020
      • study_drugFT-4202
      • disease_conditionSickle Cell
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameFT 4202
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmctafrica.regarchive@mct-cro.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantOgutu Bernhards Ragama
      • declaration_date119-01-2023
      • declaration_principal_investigatorOgutu Bernhards Ragama
      • declaration_date219-01-2023
      • placebo_presentYes
      • study_objectives<p>\n To assess the efficacy of FT-4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb)</p>\n<p>\n To assess the efficacy of FT-4202 as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate</p>\n<p>\n To measure the effects of FT-4202 on clinical measures and sequelae of hemolysis</p>\n<p>\n To evaluate the effects of FT-4202 on the sequelae of VOC</p>\n<p>\n To assess changes in fatigue of sickle cell patients taking FT-4202</p>\n<p>\n To measure additional effects of FT-4202 on clinical measures and sequelae of hemolysis</p>\n<p>\n To evaluate the duration of improvement in Hb from FT-4202</p>\n<p>\n To evaluate additional effects of FT-4202 on transfusion use •</p>\n<p>\n To evaluate the effects of FT-4202 on hospitalization</p>\n<p>\n To evaluate the effects of FT-4202 on types and duration of VOC</p>\n<p>\n To evaluate the effects of FT-4202 on opioid usage</p>\n
      • principal_inclusion_criteria<p>\n PRINCIPAL INCLUSION CRITERIA * Participants are eligible to be included in the study only if all the following criteria apply: Informed Consent</p>\n<p>\n 1. Patient has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each patient; in the case of adolescent patients, both the consent of the patient’s legal representative or legal guardian, and the patient’s assent must be obtained) Age</p>\n<p>\n 2. Age 12 to 65 years, inclusive, at time of randomization Type of Participant and Disease Characteristics</p>\n<p>\n 3. Patient has a confirmed diagnosis of sickle cell disease • Documentation of SCD genotype (HbSS, HbSβ0 -thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing; if unavailable, must be confirmed by laboratory testing during screening</p>\n<p>\n 4. Patient has had at least 2 episodes of VOC in the past 12 months • For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis (for which there was no explanation other than VOC) which required prescription or healthcare professional-instructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening)</p>\n<p>\n 5. Hemoglobin ≥ 5.5 and ≤ 10 g/dL (≥ 55 and ≤ 100 g/L) during screening</p>\n<p>\n 6. For participants taking HU, the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study, in the opinion of the Investigator Sex and Contraceptive/Barrier Requirements</p>\n<p>\n 7. Patients, who if female and of child bearing potential, are using highly effective methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug</p>\n
      • principal_exclusion_criteria<p>\n PRINCIPAL EXCLUSION CRITERIA * Medical Conditions</p>\n<p>\n 1. More than 10 VOCs (as defined in Inclusion Criterion 4) within the past 12 months</p>\n<p>\n 2. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF</p>\n<p>\n 3. Female who is breast feeding or pregnant</p>\n<p>\n 4. Hepatic dysfunction characterized by: • Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) • Direct bilirubin > 3.0 × ULN</p>\n<p>\n 5. Patients with clinically significant bacterial, fungal, parasitic, or viral infection requiring systemic therapy • Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening/enrollment until active therapy has been completed Note: Infection prophylaxis is allowed (see concomitant medication restrictions)</p>\n<p>\n 6. Known human immunodeficiency virus (HIV) positivity</p>\n<p>\n 7. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and and hepatitis B core antibody [HepBcAb] positive)</p>\n<p>\n 8. Active hepatitis C infection</p>\n<p>\n 9. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory < 30 mL/min/1.73 m2 ) or on chronic dialysis</p>\n<p>\n 10. History of malignancy within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation • Patients with malignancy considered surgically cured are eligible (eg, nonmelanoma skin cancer, cancer of the cervix in-situ, ductal carcinoma in situ [stage 1], grade 1 endometrial cancer)</p>\n<p>\n 11. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following: • Unstable angina pectoris or myocardial infarction or elective coronary intervention • Congestive heart failure requiring hospitalization • Uncontrolled clinically significant arrhythmias • Symptomatic pulmonary hypertension hepatitis B core antibody [HepBcAb] positive)</p>\n<p>\n 12. History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage</p>\n<p>\n 13. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)</p>\n<p>\n 14. Patients with iron deficiency (eg, serum iron less than the lower limit of normal [LLN] or ferritin <10 µg/L) who are not taking or are unable to take iron supplements at the time of consent and during the study</p>\n<p>\n 15. Patients with folate (or folic acid or Vitamin B9) or Vitamin B12 deficiency (eg, folate or Vitamin B12 levels less than the LLN) who are not taking or are unable to take supplements before the first dose of study drug and during the study</p>\n<p>\n 16. Patients who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended Prior/Concomitant Therapy</p>\n<p>\n 17. Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) • Patients who have received an RBC transfusion for any reason within 60 days of the Screening period are eligible if HbA (adult Hb) < 10% by Hb electrophoresis before start of study treatment</p>\n<p>\n 18. Receiving or use of concomitant medications that are strong inducers or moderate/strong inhibitors of CYP3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study</p>\n<p>\n 19. Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study</p>\n<p>\n 20. Use of a selectin antagonist (eg, crizanlizumab or other monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study</p>\n<p>\n 21. Use of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study</p>\n<p>\n 22. Receipt of prior cellular-based therapy (eg, hematopoietic cell transplant, gene modification therapy) Prior/Concurrent Clinical Study Experience</p>\n<p>\n 23. Participated in another clinical trial of an investigational agent (or medical device) within 28 days or 5 half-lives of first dose of study drug, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device) Other Exclusions</p>\n<p>\n 24. Inadequate venous access as determined by the Investigator/ site staff</p>\n<p>\n 25. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent</p>\n
      • primary_end_points<p>\n Hb response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period</p>\n<p>\n Annualized VOC rate during the 52-week blinded treatment period based on adjudicated VOC review</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n  Principal Investigator Dr. Bernhards Ogutu MBChB, Mmed(Paed), PhD 30 years</p>\n<p>\n Sub-Investigator Dr Godfrey Allan Otieno MBChB, Mmed(Paed) 20 years</p>\n<p>\n Sub-Investigator Dr John Orimbo Guda MBChB 2 years</p>\n<p>\n Sub-Investigator Dr Fredrick Olewe MBChB 5 years</p>\n<p>\n Pharmacist Ruth Ongoro Wasuna Bpharm, MBA 20 years</p>\n<p>\n Study Coordinator Ishmael Osoo Sports BScN 15 years</p>\n<p>\n Lab Technologist Pretvine Okello Diploma Lab Sciences 2 years</p>\n<p>\n Lab Technologist Linah Achieng Oluoch Diploma Lab Sciences 2 years</p>\n<p>\n Study Nurse Jane Olum Higher Diploma in Nursing 15 years</p>\n<p>\n Study Nurse Oliver Akach Diploma Nursing 3 years</p>\n<p>\n Study Clinician Nashon Okello Diploma Clinical Medicine 2 years</p>\n<p>\n Field Assistant Pamela Atieno Diploma Community Development 2 years</p>\n<p>\n Field Assistant Caroline Atieno Certificate Computers Applications 2 year</p>\n<p>\n Data Entry clerk Nerea Omondi Diploma Community Development 20 years</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>Site facilities</strong></p>\n<p>\n <strong>1. </strong>Laboratory</p>\n<p>\n 2. Pharmacy</p>\n<p>\n 3. Emergency center and facilities</p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n Oman: Turkey: KSA:</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n NA</p>\n
      • estimated_duration104 Weeks
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo Controlled
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states8
      • number_of_sites4
      • multi_country_listOman, KSA, Nigeria, Ghana, Egypt, Turkey, Kenya, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNot competitive enrolment
      • total_participants_worldwide344
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyParticipant under the age of 18
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameOgutu Ragama
      • investigator1_middle_nameBernhards
      • investigator1_family_nameRagama
      • investigator1_qualificationMMED Paeds
      • investigator1_professional_addressP. O. Box 2254 Nairobi or P.O. Box 54, Kisumu
      • investigator1_telephone+254-35-22942/254-733-812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants30
      • notification
      • approval_date24-05-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted24-01-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed conclusively.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-16 16:39:57
      • created2023-01-18 10:02:32
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id881
        • application_id1209
        • given_nameOgutu
        • middle_nameBernhards
        • family_nameRagama
        • qualificationMMED Paeds
        • professional_addressP. O. Box 2254 Nairobi or P.O. Box 54, Kisumu
        • telephone+254-35-22942/254-733-812613
        • emailogutu6@gmail.com
        • created2023-01-18 11:07:53
        • modified2023-01-24 11:41:35
    • SiteDetail(array)
      • 0(array)
        • id1389
        • application_id1209
        • county_id42
        • site_nameKondele Children\'s Hospital Center for Clinical Research (CCR),
        • physical_addressP.O Box 54-40100 PO Box 54-40100 Kisumu,
        • contact_details254-733-812613
        • contact_personDr. Ogutu Bernhards
        • site_capacity(null)
        • misc(null)
        • created2023-01-18 11:07:53
        • modified2023-01-24 11:41:35
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1390
        • application_id1209
        • county_id47
        • site_nameGertrude\'s Children Hospital
        • physical_address 34 MUTHAIGA ROAD, NAIROBI
        • contact_detailsPO BOX 42325- 00100, +254718311709.
        • contact_personProf. Githanga Jessie
        • site_capacity(null)
        • misc(null)
        • created2023-01-18 12:48:26
        • modified2023-01-24 11:41:35
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1391
        • application_id1209
        • county_id41
        • site_nameKEMRI/CRDR Kemri Clinical Research Annex Siaya County Referral Hospital Grounds,
        • physical_address Siaya County Referral Hospital Grounds
        • contact_details0724522474
        • contact_personDr. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-01-18 12:48:26
        • modified2023-01-24 11:41:35
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 3(array)
        • id1392
        • application_id1209
        • county_id42
        • site_nameKombewa CRC
        • physical_addressP.O. Box 54-40100, Kisumu, Kenya
        • contact_detailsTel: +254 721 996988/ +254 733333530
        • contact_personDr. Oyieko
        • site_capacity(null)
        • misc(null)
        • created2023-01-18 12:48:26
        • modified2023-01-24 11:41:35
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id628
        • application_id1209
        • sponsorForma Therapeutics, Inc.
        • sponsor_typeOthers
        • contact_personDanish Khan
        • address500 Arsenal Street, Suite 100 Watertown, MA 02742
        • telephone_number617-679-1970
        • fax_number
        • cell_number617-880-9574
        • email_address4202medicalmonitor@formatherapeutics.com
        • created2023-01-18 11:07:53
        • modified2023-01-24 11:41:35
  • 1(array)
    • Application(array)
      • id1207
      • user_id357
      • trial_status_id1
      • abstract_of_study<div>\n <span style=\"font-size:14px;\"><strong>Study Design:</strong> An open-label, parallel-assignment, randomized clinical trial of 1sttrimester </span><span style=\"font-size: 14px;\">active screening for malaria parasites on adverse pregnancy outcome. </span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size: 14px;\"><strong>Study Phase:</strong> 4</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Study Population:</strong> Pregnant women in the 1st trimester of all gravidities in </span><span style=\"font-size: 14px;\">areas of moderate to high P. falciparum transmission the intensity in Kenya and the </span><span style=\"font-size: 14px;\">Democratic Republic of the Congo. A total of >2000 women (# paucigravidae for </span><span style=\"font-size: 14px;\">primary analysis: 1368).</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Number of Sites:</strong> 2: Kenya and DRC</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Description of Study Product or Intervention:</strong> Testing capillary blood for P. falciparum </span><span style=\"font-size: 14px;\">parasites using a high-sensitivity rapid diagnostic test (HS-RDT)</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Study Objectives:</strong> Primary: Composite adverse pregnancy outcome of: low birthweight </span><span style=\"font-size: 14px;\">(LBW, < 2500 g) or preterm (PT, <37 0/7 wk) or small for gestational age (SGA, < 10th </span><span style=\"font-size: 14px;\">percentile for gestational age) or pregnancy loss or neonatal death (live birth with death </span><span style=\"font-size: 14px;\">< 28d) Secondary: Individual components of the primary outcome, birthweight </span><span style=\"font-size: 14px;\">(continuous), gestational age (continuous), adverse newborn outcome (live birth with </span><span style=\"font-size: 14px;\">LBW/PT/SGA), perinatal mortality (stillbirth or neonatal death), neonatal death (live birth </span><span style=\"font-size: 14px;\">with death < 28d), malaria at delivery and maternal malaria.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Duration of Individual Subject Participation:</strong> Up to 42 weeks: up to 38 weeks gestation + </span><span style=\"font-size: 14px;\">4 weeks postdelivery</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Estimated Time to Last Subject/Last Study Day: </strong>2 year</span></div>\n
      • study_title<div>\n <span style=\"font-size:14px;\">Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy with High-Sensitivity Diagnostics (INTREPiD).</span></div>\n
      • laymans_summary<p>\n <span style=\"font-size:14px;\">INTREPiD is a randomized clinical trial of malaria testing during the 1^st trimester of pregnancy. The study will test if we can improve pregnancy outcomes using a strategy of screening in the 1^st trimester for malaria parasites using new malaria rapid diagnostic tests and treating the infected women.  The goal of this trial is to identify new interventions to prevent the consequences of antenatal malaria during the important 1^st trimester.</span></p>\n
      • short_titleINTREPiD
      • protocol_noECCT/23/02/03
      • version_no1.0
      • date_of_protocol01-08-2022
      • study_drugAL
      • disease_conditionMalaria
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device1
      • product_type_chemical_nameCoartem
      • product_type_medical_device_nameHS-RDT Nx Tek by Abott
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjosepeddykipkoech@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
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      • applicant_investigators_brochure1
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      • applicant_hard_copies(null)
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      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantJoseph Kipkoech
      • declaration_date115-02-2023
      • declaration_principal_investigatorDr. Jeremiah Laktabai
      • declaration_date215-02-2023
      • placebo_presentNo
      • study_objectives<div>\n The objective of INTREPiD is to test the effect on pregnancy outcome in P. falciparumendemic areas of a strategy of 1st trimester screening for P. falciparum parasites with a high-sensitivity rapid diagnostic test.</div>\n<div>\n  </div>\n<div>\n <div>\n 3.2.1 Primary</div>\n <div>\n The primary objective of INTREPiD is to test if, compared to usual ANC, a strategy of 1st trimester screening of pregnant women with an HS-RDT for P. falciparum infection followed by treatment if positive with Artemether-Lumefantrine reduces the risk of an adverse pregnancy outcome.</div>\n <div>\n  </div>\n <div>\n 3.2.2 Secondary</div>\n <div>\n Secondary objectives of INTREPiD are to test if 1st trimester screening with an HS-RDT and treatment if positive with AL reduces the risks of an array of maternal, fetal, and safety outcomes (see Section 3.3.2).</div>\n <div>\n  </div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n Eligibility Criteria</div>\n<div>\n  </div>\n<div>\n 5.1.1 Subject Inclusion Criteria</div>\n<div>\n  </div>\n<div>\n Women will be eligible to enroll in INTREPiD if they meet all of the inclusion criteria:</div>\n<div>\n  </div>\n<div>\n 1. Aged between 16 years and 40 years (inclusive)</div>\n<div>\n 2. Viable singleton pregnancy with gestational age estimated less than 13 6/7 weeks (inclusive) by ultrasound</div>\n<div>\n 3. HIV-uninfected</div>\n<div>\n 4. Willing to participate in the study schedule</div>\n<div>\n 5. Planning to remain in the study area for the duration of pregnancy and 1 month after delivery</div>\n<div>\n 6. Willing to deliver in a study-affiliated health facility</div>\n<div>\n  </div>\n<div>\n  </div>\n
      • principal_exclusion_criteria<div>\n 5.1.2 Subject Exclusion Criteria</div>\n<div>\n Women will be ineligible to enroll in INTREPiD if they meet any of the exclusion criteria:</div>\n<div>\n 1. High risk pregnancy that requires referral for specialized care by local guidelines</div>\n<div>\n 2. Active medical problem at the time of screening requiring higher level care</div>\n<div>\n 3. Antimalarial receipt in the 2 weeks prior to screening</div>\n<div>\n 4. Past allergy to Artemether or Lumefantrine or another condition that prohibits the</div>\n<div>\n receipt of either drug</div>\n<div>\n 5. Current participation in another clinical research study</div>\n
      • primary_end_points<div>\n <strong>3.3.1 Primary</strong></div>\n<div>\n  </div>\n<div>\n The primary outcome is a composite adverse pregnancy outcome comprised of:</div>\n<div>\n 1. Low birthweight (LBW), defined as < 2500 grams OR</div>\n<div>\n 2. Preterm (PT), defined as < 37 0/7 weeks OR</div>\n<div>\n 3. Small for gestational age (SGA), defined as < 10th percentile weight for GA OR</div>\n<div>\n 4. Pregnancy loss, defined as</div>\n<div>\n a. Spontaneous abortion (loss < 22 0/7 weeks gestation) OR</div>\n<div>\n b. Stillbirth (loss ≥ 22 0/7 weeks gestation) OR</div>\n<div>\n  </div>\n<div>\n 5. Neonatal death, defined as livebirth with death prior to the 28th day of life. The rationales for such a complex composite outcome are that: i) antenatal malaria has</div>\n<div>\n been associated with an increased risk of each of these outcomes (see Section 2.1.3), ii) this comprehensively captures objective adverse outcomes that are priorities for women and providers, iii) the outcome is similar to contemporary trials of MiP prevention, and iv) the outcomes can be plausibly measured in austere settings.</div>\n<div>\n  </div>\n<div>\n <strong>3.3.2 Secondary</strong></div>\n<div>\n Secondary outcomes will include efficacy measures for the fetus/offspring and the mother as well as safety outcomes.</div>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
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      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n George Mudi - Clinical Officer  with over 2 years experience</p>\n<p>\n Brian Siundu - CKinical Officer  with over 2 years experience</p>\n<p>\n Sophia Yego - Clinical Officer  with over 2 years experience</p>\n<p>\n Anthoney Opon -  Nurse with over 2 years experience</p>\n
      • other_details_explanation<p>\n <span style=\"font-family:arial,helvetica,sans-serif;\">The purpose of the INTREPiD study is to compare against usual antenatal care the efficacy of a strategy of 1st trimester screening for malaria parasites with a highsensitivity malaria rapid diagnostic test followed by treatment of test-positive women with artemether-lumefantrine (AL) on a composite outcome of adverse pregnancy outcome comprising low birth weight, small for gestational age, preterm, fetal loss, or neonatal death. The Hypothesis is that, compared to usual antenatal care, screening women in the 1st trimester for P. falciparum and treating them if positive with AL will r</span><span style=\"font-family: arial, helvetica, sans-serif;\">educe the risk of an adverse pregnancy outcome.</span><span style=\"font-family: arial, helvetica, sans-serif; color: rgb(51, 51, 51); font-size: 12.5px;\"> For this reason, the Duke Clinical Research Institute (the sponsor-investigator) has partnered with colleagues at Moi University with expertise in Malaria in pregnancy to enroll patients in Bungoma. Bungoma-Kenya provides a favourable ground to conduct this trials as the region experience a consistently high prevalence of malaria all year round and suitable for recruiting 1st trimester pregnant women. </span></p>\n
      • other_details_regulatory_notapproved<p>\n NACOSTI</p>\n
      • other_details_regulatory_approved<p>\n IREC -  MTRH/Moi</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n NA</p>\n
      • estimated_duration3 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorUsual care
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaBungoma County
      • single_site_physical_addressWebuye County Hospital
      • single_site_contact_personJoseph Kipkoech
      • single_site_telephone0720393547
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site1244
      • total_participants_worldwide2488
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJeremiah
      • investigator1_middle_nameK
      • investigator1_family_nameLaktabai
      • investigator1_qualificationMD
      • investigator1_professional_addressMoi University School of Medicine
      • investigator1_telephone0722685542
      • investigator1_emailjklaktabai@gmail.com
      • organisations_transferred_Yes
      • number_participants1244
      • notification
      • approval_date23-07-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted15-02-2023
      • is_child0
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      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed
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      • quantity_destroyed(null)
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      • balance_site(null)
      • final_date(null)
      • modified2024-09-03 08:22:39
      • created2023-01-16 12:41:54
      • total_sites(null)
      • ecitizen_invoice(null)
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      • 0(array)
        • id897
        • application_id1207
        • given_nameSteve
        • middle_nameM
        • family_nameTaylor
        • qualificationMD
        • professional_addressDuke University
        • telephone+19198245232
        • emailsteve.taylor@duke.edu
        • created2023-02-07 12:07:48
        • modified2023-02-15 13:52:42
      • 1(array)
        • id901
        • application_id1207
        • given_nameJeremiah
        • middle_nameK
        • family_nameLaktabai
        • qualificationMD
        • professional_addressMoi University
        • telephone0722685542
        • emailjklaktabai@gmail.com
        • created2023-02-09 11:54:45
        • modified2023-02-15 13:52:42
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        • application_id1207
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        • created2023-02-07 12:07:48
        • modified2023-02-15 13:52:42
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        • sponsorDuke Clinical Research Institute (DCRI)
        • sponsor_typeResearch Institution
        • contact_personTaylor Steve
        • addressDuke University
        • telephone_number+19198245232
        • fax_number
        • cell_number+19198245232
        • email_addresssteve.taylor@duke.edu
        • created2023-02-07 12:07:48
        • modified2023-02-15 13:52:42
  • 2(array)
    • Application(array)
      • id1199
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      • abstract_of_study<div>\n <span style=\"color:#000000;\">A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH TERIFLUNOMIDE IN ADULT PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS</span></div>\n<div>\n  </div>\n<div>\n <span style=\"color:#000000;\">and</span></div>\n<div>\n  </div>\n<div>\n <span style=\"color:#000000;\">CSF BIOMARKER SUBSTUDY ASSOCIATED WITH A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY (GN41851) TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH TERIFLUNOMIDE IN ADULT PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS</span></div>\n<div>\n  </div>\n<div>\n <div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span style=\"color:#000000;\">PROTOCOL NUMBER: GN41851</span></div>\n <div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <span style=\"color:#000000;\">STUDY NAME: FENHANCE</span></div>\n <div>\n <span style=\"color:#000000;\">VERSION NUMBER: 4 and 2 respectively</span></div>\n <div>\n <span style=\"color:#000000;\">TEST COMPOUND(S): Fenebrutinib (RO7010939)</span></div>\n <div>\n  </div>\n <div>\n <span style=\"color:#000000;\">Find attached (in the checklist section) the document titled: <u><strong>9Dec20 Rationale for Fenebrutinib RMS Phase III Program</strong></u> that contains more details on the clinical trial rationale.</span></div>\n </div>\n</div>\n<p>\n  </p>\n
      • study_title<div>\n A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH TERIFLUNOMIDE IN ADULT PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS</div>\n<div>\n  </div>\n<div>\n <div>\n CSF BIOMARKER SUBSTUDY ASSOCIATED WITH A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY (GN41851) TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH TERIFLUNOMIDE IN ADULT PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS</div>\n</div>\n<p>\n  </p>\n
      • laymans_summary<div>\n Study GN41851 is a Phase III, randomized, multicenter, double-blind, double-dummy, parallel-group study to evaluate the efficacy and safety of fenebrutinib compared with teriflunomide in adult patients with RRMS and active secondary progressive MS, collectively referred to as RMS. All eligible patients will be randomized 1:1 through an interactive voice or web-based response system (IxRS) to either one of two arms:</div>\n<ul>\n <li>\n Fenebrutinib treatment arm: fenebrutinib (200 mg by mouth [PO] BID) with teriflunomide-matching placebo</li>\n <li>\n Teriflunomide treatment arm: teriflunomide (14 mg PO QD) with fenebrutinib-matching placebo</li>\n</ul>\n<div>\n Approximately 736 patients will be enrolled and will be recruited globally. Patients who discontinue study treatment early or who discontinue from the study for any reason will not be replaced.</div>\n<div>\n This study will consist of the following phases:</div>\n<ul>\n <li>\n Screening phase</li>\n <li>\n Double-blind treatment (DBT) phase</li>\n <li>\n Post-DBTsafety follow-up (post-DBTSFU) phase</li>\n <li>\n Optional open-label extension (OLE) phase</li>\n <li>\n OLE safety follow-up (OLE-SFU) phase</li>\n</ul>\n<div>\n The study duration will vary for each patient as a result of the primary analysis being event driven.</div>\n<p>\n Randomization will be stratified according to the following criteria:</p>\n<ul>\n <li>\n Global Region (United States vs. non-United States)</li>\n <li>\n EDSS score (more than 4.0 vs. less than or equal to 4.0)</li>\n <li>\n Presence or absence of T1Gd+ lesions at screening</li>\n</ul>\n<div>\n Patient safety will be monitored by an iDMC both for the iDMC-ISA and at regular intervals throughout the DBT phase.</div>\n<div>\n  </div>\n<div>\n Study GN41851 will enroll patients globally. Enrollment will be globally competitive. After completion of the global enrollment phase, additional patients may be enrolled in an extended China enrollment phase at sites in mainland China, Hong Kong, and Taiwan that are recognized by China’s National Medical Products Administration to ensure a total enrollment that is sufficient to support registration in China. Thus, the China subpopulation may include</div>\n<div>\n patients enrolled at sites in China during both the global enrollment phase and the China extension phase. Patients from the China extension phase will be randomized in a 1:1 ratio to the two treatment arms and follow the same schedule of activities as in the global study.</div>\n<div>\n  </div>\n<div>\n Analyses based on the China extension phase will be reported separately from the global study.</div>\n<div>\n  </div>\n<div>\n <div>\n <u><strong>End of Study</strong></u></div>\n <div>\n The end of this study is defined as the date when the last patient, last visit (LPLV) occurs in the OLE phase or the LPLV in the OLE-SFU phase, whichever occurs later.</div>\n <div>\n  </div>\n <div>\n <u><strong>Length of Study</strong></u></div>\n <div>\n The estimated duration of the DBT phase will be approximately 236 weeks or approximately 4.5 years (assuming last patient randomized after 140 weeks  96 weeks of DBT for the last patient into the study). The estimated maximum length of the study, from screening of the first patient to the end of the study, is expected to be approximately 340 weeks or approximately 6.5 years (assuming 140 weeks of recruitment + 96 weeks of DBT + 96 weeks in OLE+ 8 weeks of OLE SFU for the last patient into study). In addition, the Sponsor may decide to terminate the study at any time.</div>\n</div>\n<p>\n  </p>\n
      • short_titleFENHANCE
      • protocol_noECCT/23/01/06
      • version_no4 and 2 respectively
      • date_of_protocol20-08-2021
      • study_drugFenebrutinib (RO7010939)
      • disease_conditionRELAPSING MULTIPLE SCLEROSIS
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameteriflunomide (or matching placebo)
      • comparator_registeredNot registered in Kenya
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressfaith.wanjau@roche.con
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
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      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
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      • applicant_complete_form(null)
      • applicant_impd1
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      • applicant_stability_data1
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      • applicant_dsmb_charter1
      • applicant_detailed_budget1
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      • declaration_applicantFaith Wanjau
      • declaration_date116-12-2022
      • declaration_principal_investigatorProf. Mansoor Saleh
      • declaration_date216-12-2022
      • placebo_presentYes
      • study_objectives<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">This study will evaluate the efficacy and safety of fenebrutinib compared with teriflunomide in </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">adult patients with relapsing multiple sclerosis (RMS). The pharmacokinetics (PK) of </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">fenebrutinib will also be evaluated.</span></p>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; text-decoration-line: underline; text-decoration-skip-ink: none; vertical-align: baseline; white-space: pre-wrap;\">Primary Efficacy Objective</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The primary efficacy objective for this study is to evaluate the efficacy of fenebrutinib compared </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">with teriflunomide on the basis of the following primary endpoint of Annualized relapse rate </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">(ARR).</span></p>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; text-decoration-line: underline; text-decoration-skip-ink: none; vertical-align: baseline; white-space: pre-wrap;\">Secondary Efficacy Objective</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The secondary efficacy objective for this study is to evaluate the efficacy of fenebrutinib </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">treatment compared with teriflunomide on the basis of the following endpoints:</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\"> Time to onset of composite 12-week confirmed disability progression (cCDP12) defined as the time from baseline to the first occurrence of a progression event according to at least one of the following three criteria; must be confirmed at a regularly scheduled visit that is at least 12 weeks after the initial disability progression:</span></span></p>\n </li>\n</ul>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">– An increase from baseline in Expanded Disability Status Scale (EDSS) score of</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\"> 1.0 point in patients with a baseline EDSS score of  5.5 or an increase of  0.5 points</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">in patients with a baseline EDSS score of  5.5 (confirmed disability progression</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">[CDP])</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">–  20% increase in 12-week confirmed timed 25-foot walk test (T25FWT)</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">–  20% increase from baseline in time to complete the 9-hole peg test (9-HPT)</span></span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of composite 24-week confirmed disability progression (cCDP24)</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of 12-week confirmed disability progression (CDP12), defined as an increase from baseline in EDSS score of  1.0 point in patients with a baseline EDSS score of  5.5 or an increase  0.5 points in patients with a baseline EDSS score of  5.5</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of 24-week CDP (CDP24)</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Total number of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd+) as detected by magnetic resonance imaging (MRI)</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Total number of new and/or enlarging T2-weighted lesions as detected by MRI</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Rate of percent change in total brain volume from Week 24 as assessed by MRI</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change in patient-reported physical impacts of MS, as measured by the Multiple Sclerosis</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Impact Scale (29-Item), Version 2 (MSIS-29 v2) physical scale</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modalities Test</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">(SDMT) score</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change from baseline to Week 48 in the concentration of serum neurofilament light chain (NfL)</span></span></p>\n </li>\n</ul>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The secondary endpoints above do not reflect order of statistical hierarchy. The statistical hierarchy for the secondary endpoints is further discussed in the protocol, and details can be found in the Statistical Analysis Plan (SAP).</span></span></p>\n<p>\n <br />\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Exploratory Efficacy Objective</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The exploratory efficacy objective for this study is to evaluate the efficacy of fenebrutinib </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">compared with teriflunomide based on, but not limited to, the following endpoints:</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients with worsening in SDMT by 4 points</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of  20% increase in 12-week confirmed T25FWT</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of  20% increase in 12-week confirmed 9-HPT</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of  20% increase in 24-week confirmed T25FWT</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of  20% increase in 24-week confirmed 9-HPT</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients with a meaningful deterioration from baseline in patient-reported</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">psychological impacts of MS, as assessed by the MSIS-29 v2 psychological scale at</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Week 96</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Total number of new T1-hypointense lesions (black holes) from baseline as detected by</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">MRI</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients who are free of protocol-defined relapse at Week 96 and at the time</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">of clinical cutoff of the primary analysis</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients with a meaningful deterioration from baseline in patient-reported</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">physical impacts of MS, as assessed by the MSIS-29 v2 physical scale, at Week 96</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients free of disability progression, as assessed by cCDP12, cCDP24,</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">CDP12, and CDP24, at Week 96 and at the time of clinical cutoff of primary analysis</span></span></p>\n </li>\n</ul>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Note: In this study, the screening MRI measurements are used as the baseline measurements</span></span></p>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Safety Objective</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The safety objective for this study is to evaluate the safety of fenebrutinib compared with </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">teriflunomide on the basis of the following endpoints:</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The nature, frequency, timing, and severity of adverse events; serious adverse events; and </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">adverse events leading to study treatment discontinuation or dose interruptions</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change from baseline in targeted vital signs</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change from baseline in targeted ECG parameters</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change from baseline in clinical laboratory results</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients with suicidal ideation or behavior, as assessed by the</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Columbia-Suicide Severity Rating Scale (C-SSRS)</span></span></p>\n </li>\n</ul>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Pharmacokinetic Objectives</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The PK objective for this study is to characterize the fenebrutinib PK profile on the basis of the </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">following endpoint:</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Plasma concentration of fenebrutinib at specified timepoints</span></span></p>\n </li>\n</ul>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Sparse PK samples will be collected in all patients. However, to better characterize fenebrutinib </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">PK in patients with MS, more intensive PK samples will be collected in a small subset of </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">patients who consent for further evaluation.</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The exploratory PK objectives for this study are as follows:</span></span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">To evaluate potential relationships between drug exposure and the efficacy and safety of fenebrutinib on the basis of the following endpoints:</span></span></p>\n </li>\n</ul>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">– Relationship between plasma concentrations of fenebrutinib and efficacy endpoints</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">– Relationship between plasma concentrations of fenebrutinib and safety endpoints</span></span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">To evaluate potential relationships between selected covariates and exposure to fenebrutinib on the basis of the following endpoint:</span></span></p>\n </li>\n</ul>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">– Relationship between selected covariates and plasma concentrations of fenebrutinib</span></span></p>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">BIOMARKER OBJECTIVE</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The exploratory biomarker objective for this study is to identify and/or evaluate biomarkers that </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">are predictive of response to fenebrutinib (i.e., predictive biomarkers), are early surrogates of </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">efficacy, are associated with progression to a more severe disease state (i.e., prognostic </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">biomarkers), are associated with acquired resistance to fenebrutinib, are associated with </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">susceptibility to developing adverse events or can lead to improved adverse event monitoring or </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">investigation, can provide evidence of fenebrutinib activity (i.e., pharmacodynamic [PD] </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">biomarkers), or can increase the knowledge and understanding of disease biology and drug</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">safety. Biomarker endpoints may include, but are not limited to, the following endpoints:</span></span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Relationship between baseline biomarkers in blood (serum and/or plasma) and efficacy,</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">PK, or other biomarker endpoints</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Relationship between change from baseline to post treatment sampling in blood biomarkers (serum and/or plasma) and efficacy, PK, or other biomarker endpoints</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Relationship between genetics (including, but not limited to human leukocyte antigen genotype) efficacy, PK, or other biomarker endpoints</span></span></p>\n </li>\n</ul>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Exploratory biomarker analysis results may be reported separately from the GN41851 clinical </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">study report.</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">HEALTH STATUS UTILITY OBJECTIVE</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The exploratory health status utility objective for this study is to evaluate health status utility </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">scores of patients treated with fenebrutinib on the basis of the following endpoints:</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Relationship between EuroQol 5 Dimension, 5 Level Questionnaire (EQ 5D 5L) index score and clinical measurements that may support pharmacoeconomic modeling</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Number of hospitalizations (e.g., collected since the last clinical visit)</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-207bf30c-7fff-4f06-a548-95571a093092\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Number of emergency room visits</span></span></p>\n </li>\n</ul>\n
      • principal_inclusion_criteria<p 1ex=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n Inclusion Criteria:</p>\n<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in < 240 seconds.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Ability to perform the Timed 25-Foot Walk Test (T25FWT) in <150 seconds.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.</li>\n</ul>\n
      • principal_exclusion_criteria<p 0ex=\"\" 0px=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n Exclusion Criteria:</p>\n<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Disease duration of > 10 years from the onset of symptoms and an EDSS score at screening < 2.0.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Female participants who are pregnant or breastfeeding, or intending to become pregnant.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Male participants who intend to father a child during the study.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n A diagnosis of PPMS or non-active SPMS.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Any known or suspected active infection at screening, including but not limited to a positive screening tests for Hepatitis B and C, an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML).</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n History of cancer including hematologic malignancy and solid tumors within 10 years of screening.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Known presence of other neurological disorders, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Hypoproteinemia.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Participants with severe renal or hepatic disease impairment or Gilbert's Syndrome.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n History of alcohol or other drug abuse within 12 months prior to screening.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of HIV infection.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Inability to complete an MRI scan.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed).</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Receipt of a live-attenuated vaccine within 6 weeks prior to randomization.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period.</li>\n</ul>\n<p 0ex=\"\" 0px=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n OLE Inclusion Criteria:</p>\n<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the ATEP prior to the first administration of open-label fenebrutinib.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.</li>\n</ul>\n
      • primary_end_points<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">This study will evaluate the efficacy and safety of fenebrutinib compared with teriflunomide in </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">adult patients with relapsing multiple sclerosis (RMS). The pharmacokinetics (PK) of </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">fenebrutinib will also be evaluated.</span></p>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; text-decoration-line: underline; text-decoration-skip-ink: none; vertical-align: baseline; white-space: pre-wrap;\">Primary Efficacy Objective</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The primary efficacy objective for this study is to evaluate the efficacy of fenebrutinib compared </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">with teriflunomide on the basis of the following primary endpoint of Annualized relapse rate </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">(ARR).</span></p>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; text-decoration-line: underline; text-decoration-skip-ink: none; vertical-align: baseline; white-space: pre-wrap;\">Secondary Efficacy Objective</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The secondary efficacy objective for this study is to evaluate the efficacy of fenebrutinib </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">treatment compared with teriflunomide on the basis of the following endpoints:</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\"> Time to onset of composite 12-week confirmed disability progression (cCDP12) defined as the time from baseline to the first occurrence of a progression event according to at least one of the following three criteria; must be confirmed at a regularly scheduled visit that is at least 12 weeks after the initial disability progression:</span></span></p>\n </li>\n</ul>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">– An increase from baseline in Expanded Disability Status Scale (EDSS) score of </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">1.0 point in patients with a baseline EDSS score of  5.5 or an increase of  0.5 points </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">in patients with a baseline EDSS score of  5.5 (confirmed disability progression </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">[CDP])</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">–  20% increase in 12-week confirmed timed 25-foot walk test (T25FWT)</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">–  20% increase from baseline in time to complete the 9-hole peg test (9-HPT)</span></span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of composite 24-week confirmed disability progression (cCDP24)</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of 12-week confirmed disability progression (CDP12), defined as an increase from baseline in EDSS score of  1.0 point in patients with a baseline EDSS score of  5.5 or an increase  0.5 points in patients with a baseline EDSS score of  5.5</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of 24-week CDP (CDP24)</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Total number of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd+) as detected by magnetic resonance imaging (MRI)</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Total number of new and/or enlarging T2-weighted lesions as detected by MRI</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Rate of percent change in total brain volume from Week 24 as assessed by MRI</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change in patient-reported physical impacts of MS, as measured by the Multiple Sclerosis</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Impact Scale (29-Item), Version 2 (MSIS-29 v2) physical scale</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modalities Test</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">(SDMT) score</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change from baseline to Week 48 in the concentration of serum neurofilament light chain (NfL)</span></span></p>\n </li>\n</ul>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The secondary endpoints above do not reflect order of statistical hierarchy. The statistical hierarchy for the secondary endpoints is further discussed in the protocol, and details can be found in the Statistical Analysis Plan (SAP).</span></span></p>\n<p>\n <br />\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Exploratory Efficacy Objective</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The exploratory efficacy objective for this study is to evaluate the efficacy of fenebrutinib </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">compared with teriflunomide based on, but not limited to, the following endpoints:</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients with worsening in SDMT by 4 points</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of  20% increase in 12-week confirmed T25FWT</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of  20% increase in 12-week confirmed 9-HPT</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of  20% increase in 24-week confirmed T25FWT</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Time to onset of  20% increase in 24-week confirmed 9-HPT</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients with a meaningful deterioration from baseline in patient-reported</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">psychological impacts of MS, as assessed by the MSIS-29 v2 psychological scale at</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Week 96</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Total number of new T1-hypointense lesions (black holes) from baseline as detected by</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">MRI</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients who are free of protocol-defined relapse at Week 96 and at the time</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">of clinical cutoff of the primary analysis</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients with a meaningful deterioration from baseline in patient-reported</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">physical impacts of MS, as assessed by the MSIS-29 v2 physical scale, at Week 96</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients free of disability progression, as assessed by cCDP12, cCDP24,</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">CDP12, and CDP24, at Week 96 and at the time of clinical cutoff of primary analysis</span></span></p>\n </li>\n</ul>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Note: In this study, the screening MRI measurements are used as the baseline measurements</span></span></p>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Safety Objective</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The safety objective for this study is to evaluate the safety of fenebrutinib compared with </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">teriflunomide on the basis of the following endpoints:</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The nature, frequency, timing, and severity of adverse events; serious adverse events; and </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">adverse events leading to study treatment discontinuation or dose interruptions</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change from baseline in targeted vital signs</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change from baseline in targeted ECG parameters</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Change from baseline in clinical laboratory results</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Proportion of patients with suicidal ideation or behavior, as assessed by the</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Columbia-Suicide Severity Rating Scale (C-SSRS)</span></span></p>\n </li>\n</ul>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Pharmacokinetic Objectives</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The PK objective for this study is to characterize the fenebrutinib PK profile on the basis of the </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">following endpoint:</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Plasma concentration of fenebrutinib at specified timepoints</span></span></p>\n </li>\n</ul>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Sparse PK samples will be collected in all patients. However, to better characterize fenebrutinib </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">PK in patients with MS, more intensive PK samples will be collected in a small subset of </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">patients who consent for further evaluation.</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The exploratory PK objectives for this study are as follows:</span></span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">To evaluate potential relationships between drug exposure and the efficacy and safety of fenebrutinib on the basis of the following endpoints:</span></span></p>\n </li>\n</ul>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">– Relationship between plasma concentrations of fenebrutinib and efficacy endpoints</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">– Relationship between plasma concentrations of fenebrutinib and safety endpoints</span></span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">To evaluate potential relationships between selected covariates and exposure to fenebrutinib on the basis of the following endpoint:</span></span></p>\n </li>\n</ul>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">– Relationship between selected covariates and plasma concentrations of fenebrutinib</span></span></p>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">BIOMARKER OBJECTIVE</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">The exploratory biomarker objective for this study is to identify and/or evaluate biomarkers that </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">are predictive of response to fenebrutinib (i.e., predictive biomarkers), are early surrogates of </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">efficacy, are associated with progression to a more severe disease state (i.e., prognostic </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">biomarkers), are associated with acquired resistance to fenebrutinib, are associated with </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">susceptibility to developing adverse events or can lead to improved adverse event monitoring or </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">investigation, can provide evidence of fenebrutinib activity (i.e., pharmacodynamic [PD] </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">biomarkers), or can increase the knowledge and understanding of disease biology and drug</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">safety. Biomarker endpoints may include, but are not limited to, the following endpoints:</span></span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Relationship between baseline biomarkers in blood (serum and/or plasma) and efficacy,</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">PK, or other biomarker endpoints</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Relationship between change from baseline to post treatment sampling in blood biomarkers (serum and/or plasma) and efficacy, PK, or other biomarker endpoints</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Relationship between genetics (including, but not limited to human leukocyte antigen genotype) efficacy, PK, or other biomarker endpoints</span></span></p>\n </li>\n</ul>\n<p>\n  </p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Exploratory biomarker analysis results may be reported separately from the GN41851 clinical </span></span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">study report.</span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-family: Arial; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">HEALTH STATUS UTILITY OBJECTIVE</span></span></p>\n<p dir=\"ltr\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">The exploratory health status utility objective for this study is to evaluate health status utility </span><span style=\"font-family: Arial; font-size: 11pt; white-space: pre-wrap;\">scores of patients treated with fenebrutinib on the basis of the following endpoints:</span></p>\n<ul style=\"margin-top:0;margin-bottom:0;padding-inline-start:48px;\">\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Relationship between EuroQol 5 Dimension, 5 Level Questionnaire (EQ 5D 5L) index score and clinical measurements that may support pharmacoeconomic modeling</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Number of hospitalizations (e.g., collected since the last clinical visit)</span></span></p>\n </li>\n <li aria-level=\"1\" dir=\"ltr\" style=\"list-style-type: disc; font-size: 11pt; font-family: Arial; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre;\">\n <p dir=\"ltr\" role=\"presentation\" style=\"line-height:1.38;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-15c14b80-7fff-b817-5360-9c3b72bc8071\"><span style=\"font-size: 11pt; font-variant-numeric: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;\">Number of emergency room visits</span></span></p>\n </li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n This has been provided in the Site Specific addendum</p>\n
      • other_details_explanation<p>\n Not applicable</p>\n
      • other_details_regulatory_notapproved<p>\n <google-sheets-html-origin></google-sheets-html-origin></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" dir=\"ltr\" style=\"table-layout: fixed; font-size: 10pt; font-family: Arial; width: 0px; border-collapse: collapse; border: none;\" xmlns=\"http://www.w3.org/1999/xhtml\">\n <colgroup>\n <col width=\"174\" />\n <col width=\"203\" />\n <col width=\"108\" />\n <col width=\"100\" />\n <col width=\"153\" />\n <col width=\"143\" />\n </colgroup>\n <tbody>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\">\n Country</td>\n <td data-sheets-value=\"{\" event=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\">\n Event Description</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\" submission=\"\">\n Submission Date</td>\n <td approval=\"\" data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\">\n Approval Date</td>\n <td data-sheets-value=\"{\" of=\"\" status=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold;\">\n Status of Submission</td>\n <td data-sheets-value=\"{\" number=\"\" of=\"\" per=\"\" sites=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\">\n Number of Sites per Country</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Algeria</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 17 Oct 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" under=\"\">\n Under review</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Argentina</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 07 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11 Nov 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 7</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n China</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 23 Nov 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 26 Jan 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 20</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Czechia</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" not=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" yet=\"\">\n Not yet submitted</td>\n <td data-sheets-value=\"{\" in=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" unk=\"\">\n UNK in Feasibility</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" dominican=\"\" republic=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Dominican Republic (the)</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Sep 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 02 Dec 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Egypt</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" not=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" yet=\"\">\n Not yet submitted</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Finland</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 28 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 20 Nov 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Georgia</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 10 Oct 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 22 Nov 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 5</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Germany</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 10 Dec 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 17 Feb 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" hong=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Hong Kong</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 24 Sep 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11 Dec 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 3</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Hungary</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11 Mar 2021</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 06 May 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 5</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Italy</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 09 Nov 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 28 Jan 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 15</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Kenya</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" not=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" yet=\"\">\n Not yet submitted</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 1</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Mexico</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 03 Aug 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 05 Sep 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 5</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Morocco</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" not=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" yet=\"\">\n Not yet submitted</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 5</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" netherlands=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Netherlands (the)</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 14 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Feb 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 1</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" north=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n North Macedonia</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11 Jul 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 15 Nov 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 3</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Peru</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 18 Sep 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 29 Dec 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 7</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Poland</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 21 Mar 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 03 Oct 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 12</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Portugal</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 10 Nov 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 09 Feb 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 7</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" federation=\"\" russian=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Russian Federation (the)</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 30 Nov 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 9</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Serbia</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 21 Oct 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" under=\"\">\n Under review</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 3</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Spain</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 14 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 10 Dec 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 9</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Switzerland</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 09 Dec 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 22 Jan 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Taiwan</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 12 Nov 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Dec 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; background-color: rgb(255, 255, 255);\">\n 3</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Tunisia</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 07 Nov 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" under=\"\">\n Under review</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 4</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Ukraine</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 24 Dec 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 20 Apr 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 12</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n USA</td>\n <td data-sheets-value=\"{\" protocol=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" v4=\"\">\n Protocol V4 Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Oct 2021</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Nov 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 39</td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n <google-sheets-html-origin></google-sheets-html-origin></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" dir=\"ltr\" style=\"table-layout: fixed; font-size: 10pt; font-family: Arial; width: 0px; border-collapse: collapse; border: none;\" xmlns=\"http://www.w3.org/1999/xhtml\">\n <colgroup>\n <col width=\"174\" />\n <col width=\"203\" />\n <col width=\"108\" />\n <col width=\"100\" />\n <col width=\"153\" />\n <col width=\"143\" />\n </colgroup>\n <tbody>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\">\n Country</td>\n <td data-sheets-value=\"{\" event=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\">\n Event Description</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\" submission=\"\">\n Submission Date</td>\n <td approval=\"\" data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\">\n Approval Date</td>\n <td data-sheets-value=\"{\" of=\"\" status=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold;\">\n Status of Submission</td>\n <td data-sheets-value=\"{\" number=\"\" of=\"\" per=\"\" sites=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; font-weight: bold; overflow-wrap: break-word;\">\n Number of Sites per Country</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Algeria</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 17 Oct 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" under=\"\">\n Under review</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Argentina</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 07 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11 Nov 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 7</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n China</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 23 Nov 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 26 Jan 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 20</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Czechia</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" not=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" yet=\"\">\n Not yet submitted</td>\n <td data-sheets-value=\"{\" in=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" unk=\"\">\n UNK in Feasibility</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" dominican=\"\" republic=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Dominican Republic (the)</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Sep 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 02 Dec 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Egypt</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" not=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" yet=\"\">\n Not yet submitted</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Finland</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 28 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 20 Nov 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Georgia</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 10 Oct 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 22 Nov 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 5</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Germany</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 10 Dec 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 17 Feb 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" hong=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Hong Kong</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 24 Sep 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11 Dec 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 3</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Hungary</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11 Mar 2021</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 06 May 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 5</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Italy</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 09 Nov 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 28 Jan 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 15</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Kenya</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" not=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" yet=\"\">\n Not yet submitted</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 1</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Mexico</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 03 Aug 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 05 Sep 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 5</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Morocco</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" not=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" yet=\"\">\n Not yet submitted</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 5</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" netherlands=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Netherlands (the)</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 14 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Feb 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 1</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" north=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n North Macedonia</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 11 Jul 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 15 Nov 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 3</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Peru</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 18 Sep 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 29 Dec 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 7</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Poland</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 21 Mar 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 03 Oct 2022</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 12</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Portugal</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 10 Nov 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 09 Feb 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 7</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" federation=\"\" russian=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Russian Federation (the)</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 30 Nov 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 9</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Serbia</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 21 Oct 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" under=\"\">\n Under review</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 3</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Spain</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 14 Oct 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 10 Dec 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 9</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Switzerland</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 09 Dec 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 22 Jan 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 2</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Taiwan</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 12 Nov 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Dec 2020</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom; background-color: rgb(255, 255, 255);\">\n 3</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Tunisia</td>\n <td data-sheets-value=\"{\" initial=\"\" prot=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" submission=\"\">\n Initial Submission (Prot v4)</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 07 Nov 2022</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" under=\"\">\n Under review</td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 4</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Ukraine</td>\n <td data-sheets-value=\"{\" initial=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n Initial Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 24 Dec 2020</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 20 Apr 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 12</td>\n </tr>\n <tr style=\"height: 21px;\">\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n USA</td>\n <td data-sheets-value=\"{\" protocol=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\" v4=\"\">\n Protocol V4 Submission</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Oct 2021</td>\n <td data-sheets-numberformat=\"{\" data-sheets-value=\"{\" dd=\"\" mmm=\"\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 01 Nov 2021</td>\n <td style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n  </td>\n <td data-sheets-value=\"{\" style=\"border: 1px solid rgb(204, 204, 204); overflow: hidden; padding: 0px 3px; vertical-align: bottom;\">\n 39</td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration4 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorteriflunomide
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaAga Khan University, Nairobi
      • single_site_physical_address3rd Parklands Avenue, Off Limuru Road
      • single_site_contact_personProf Mansoor Saleh
      • single_site_telephone+254 709931500
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states28
      • number_of_sites
      • multi_country_listAlgeria\nArgentina\nChina\nCzechia\nDominican Republic (the)\nEgypt\nFinland\nGeorgia\nGermany\nHong Kong\nHungary\nItaly\nKenya\nMexico\nMorocco\nNetherlands (the)\nNorth Macedonia\nPeru\nPoland\nPortugal\nRussian Federation (the)\nSerbia\nSpain\nSwitzerland\nTaiwan\nTunisia\nUkraine\nUSA
      • data_monitoring_committeeYes
      • total_enrolment_per_site15
      • total_participants_worldwide1472
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMansoor
      • investigator1_middle_name
      • investigator1_family_nameSaleh
      • investigator1_qualificationProfessor of Hematology and Oncology
      • investigator1_professional_addressAga Khan University, Nairobi, 3rd Parklands Avenue, Nairobi-Kenya
      • investigator1_telephone+254 709 93 1500
      • investigator1_emailmansoor.saleh@aku.edu
      • organisations_transferred_Yes
      • number_participants15
      • notification
      • approval_date13-06-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-01-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed adequately.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-29 17:50:27
      • created2022-12-25 00:01:00
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id875
        • application_id1199
        • given_nameMansoor
        • middle_name
        • family_nameSaleh
        • qualificationProfessor of Hematology and Oncology
        • professional_addressAga Khan University, Nairobi, 3rd Parklands Avenue, Nairobi-Kenya
        • telephone+254 709 93 1500
        • emailmansoor.saleh@aku.edu
        • created2022-12-25 00:16:19
        • modified2023-01-25 21:19:45
    • SiteDetail(array)
      • 0(array)
        • id1345
        • application_id1199
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2022-12-25 00:16:19
        • modified2023-01-25 21:19:45
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id622
        • application_id1199
        • sponsorHoffmann La Roche
        • sponsor_typeIndustry
        • contact_personSaffra Knox
        • addressThe Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya
        • telephone_number+44 7584 447418
        • fax_number
        • cell_number+44 7584 447418
        • email_addresssaffra.knox@roche.com
        • created2022-12-25 00:16:19
        • modified2023-01-25 21:19:45
  • 3(array)
    • Application(array)
      • id1197
      • user_id606
      • trial_status_id(null)
      • abstract_of_study<p>\n <strong>ABSTRACT</strong></p>\n<p>\n  </p>\n<p>\n <strong>Background:</strong> Cancer is a leading cause of death among children worldwide. Doxorubicin has been an effective backbone for several childhood cancer treatment protocols; however, cardio toxicity often limits the clinical use. Pharmacokinetics (PK) are extremely important in predicting safe and effective chemotherapy but data for Doxorubicin with regard to nutritional status and genetic polymorphisms associated with drug metabolism among different ethnicities is largely lacking.</p>\n<p>\n  </p>\n<p>\n <strong>Relevance of the study: </strong>More knowledge about the PK of Doxorubicin among children with varying ages, different nutritional profiles, as well as different ethnicities, in the view of possible genetic polymorphisms is extremely important to improve short- and long-term outcomes.  Better understanding of these variables could lead to a reduction in treatment-related toxicity and a more effective treatment for children with cancer worldwide.</p>\n<p>\n  </p>\n<p>\n <strong>Aim:</strong> We aim to evaluate the PK of Doxorubicin in children with cancer receiving Doxorubicin-based regimens in Eldoret-Kenya. The data generated will be used to determine a more appropriate Doxorubicin dosing regimen in different patient populations with respect to age, nutritional status and ethnicity. Based on a pharmacological rationale we hypothesize that PK-profiles for Doxorubicin in children with different ages, nutritional profiles and ethnicities will significantly differ.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • study_title<p>\n <strong>Pharmacokinetic profiles for Doxorubicin among children with childhood cancer in Kenya.</strong></p>\n<p>\n  </p>\n<p>\n  </p>\n
      • laymans_summary<p>\n <strong>ABSTRACT</strong></p>\n<p>\n  </p>\n<p>\n <strong>Background:</strong> Cancer is a leading cause of death among children worldwide. Doxorubicin has been an effective backbone for several childhood cancer treatment protocols; however, cardio toxicity often limits the clinical use. Pharmacokinetics (PK) are extremely important in predicting safe and effective chemotherapy but data for Doxorubicin with regard to nutritional status and genetic polymorphisms associated with drug metabolism among different ethnicities is largely lacking.</p>\n<p>\n  </p>\n<p>\n <strong>Relevance of the study: </strong>More knowledge about the PK of Doxorubicin among children with varying ages, different nutritional profiles, as well as different ethnicities, in the view of possible genetic polymorphisms is extremely important to improve short- and long-term outcomes.  Better understanding of these variables could lead to a reduction in treatment-related toxicity and a more effective treatment for children with cancer worldwide.</p>\n<p>\n  </p>\n<p>\n <strong>Aim:</strong> We aim to evaluate the PK of Doxorubicin in children with cancer receiving Doxorubicin-based regimens in Eldoret-Kenya. The data generated will be used to determine a more appropriate Doxorubicin dosing regimen in different patient populations with respect to age, nutritional status and ethnicity. Based on a pharmacological rationale we hypothesize that PK-profiles for Doxorubicin in children with different ages, nutritional profiles and ethnicities will significantly differ.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • short_titleDoxo-study
      • protocol_noECCT/24/02/05
      • version_noone
      • date_of_protocol21-12-2021
      • study_drugDoxorubicine
      • disease_conditionchildhood cancer
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameDoxorubicine
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresskugolinet@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr. Susan Nyabate
      • declaration_date115-02-2024
      • declaration_principal_investigatorDr. Festus Njuguna
      • declaration_date215-02-2024
      • placebo_presentNo
      • study_objectives<div>\n Primary Objective:</div>\n<div>\n To evaluate the PK profiles of Doxorubicin in children with cancer in Lilongwe-Malawi and Eldoret-Kenya.</div>\n<div>\n  </div>\n<div>\n Secondary objectives:</div>\n<div>\n 1. To evaluate the PK profiles of Doxorubicin and Doxorubicinol in relation to age</div>\n<div>\n 2. To evaluate the PK profiles of Doxorubicin and Doxorubicinol in relation to nutritional status</div>\n<div>\n 3. To evaluate the PK profiles of Doxorubicin and Doxorubicinol in relation to genetic</div>\n<div>\n polymorphisms</div>\n<div>\n 4. To evaluate the PK profiles of Doxorubicin and Doxorubicinol in relation to racial background.</div>\n
      • principal_inclusion_criteria<div>\n Inclusion criteria</div>\n<div>\n a) All children aged 2-18 years with cancer and receiving one dose of Doxorubicin as part of local</div>\n<div>\n standard clinical treatment protocol in Lilongwe and Eldoret.</div>\n<div>\n b) Staying at least 24h in the hospital</div>\n<div>\n c) Written informed consent.</div>\n<div>\n  </div>\n
      • principal_exclusion_criteria<div>\n Exclusion criteria</div>\n<div>\n a) Estimated glomerular filtration rate <60 ml/min/1.73m2.</div>\n<div>\n b) Known and/or pre-existing depressed cardiac function EF< 50% or clinical signs of hart failure</div>\n<div>\n c) Sepsis at time of inclusion</div>\n
      • primary_end_points<p>\n <strong>Primary outcome: </strong>Description of pharmacokinetic profiles by AUC and clearance (CL) of Doxorubicin and Doxorubicinol in children with cancer in Lilongwe-Malawi, Eldoret-Kenia and Utrecht- The Netherlands.</p>\n<p>\n  </p>\n<p>\n <strong>Secondary outcome:</strong></p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Difference AUC and CL of Doxorubicin and Doxorubicinol among children with cancer in regards to different age groups (below and above 6 years).</li>\n <li>\n Difference AUC and CL of Doxorubicin and Doxorubicinol among children with cancer in regards to severe, moderate or no malnutrition.</li>\n <li>\n Difference AUC and CL of Doxorubicin and Doxorubicinol among children with cancer in regards to pharmaco-genetic polymorphism associated with drug metabolism</li>\n <li>\n Difference AUC and CL of Doxorubicin and Doxorubicinol among children with cancer in regards to ethnicity.</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n We have 4 main staff members including a pediatrician, pharmacist, study coordinator and data assistant. The site facility is in a level six hospital, in a well equiped and aqequately staffed paediatric oncology ward.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Dr. Festus Njuguna - Pediatrician - Master of Medicine (Paediatrics) (2005-2008), Bachelor of Medicine and Bachelor Surgery (1994-2000). Has over ten years working experince as a paediatrician and 8 years as a researcher in the pediatric oncology field</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Dr. Linet Kugo - Pharmacist - Master of Pharmacy (Epivigil) (2013-2015); Bachelor of Pharmacy (2004-2008); 4 years experience as an oncology pharmacist with over 10 years experince as a pharmacist.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. Sandra Langat - Study Coordinator - Bsc. in Medical Microbiology (2004-2007), 11 years working experinece in data collection and research coordination.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4. Martha Kipngetich - Data Assistant - Diploma in Information Technology (2002-2003), BSc. in Information Technology (2014 - 2015), 10 years working experience in data management, IT administration and research.</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n none</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration12 months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaMOI UNIVERSITY SCHOOL OF MEDICINE
      • single_site_physical_addressNANDI ROAD, UASIN GISHU
      • single_site_contact_personFESTUS NJUGUNA
      • single_site_telephone0721219761
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteN/A
      • total_participants_worldwide80
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFestus
      • investigator1_middle_nameMUIGAI
      • investigator1_family_nameNJUGUNA
      • investigator1_qualificationPediatrician
      • investigator1_professional_addressMOI UNIVERSITY SCHOOL OF MEDICINE
      • investigator1_telephone0721219761
      • investigator1_emailmuigaifes2000@yahoo.com
      • organisations_transferred_No
      • number_participants80
      • notification
      • approval_date20-09-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted15-02-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApplication reviewed with a satisfactory response on evaluation comments
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-09-20 22:25:14
      • created2022-12-08 13:30:10
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id871
        • application_id1197
        • given_nameFestus
        • middle_nameMUIGAI
        • family_nameNjunguna
        • qualificationPediatrician
        • professional_addressMOI TEACHING AND REFERRAL HOSPITAL
        • telephone0721219761
        • emailmuigaifes2000@yahoo.com
        • created2022-12-08 14:00:48
        • modified2024-02-15 08:40:56
    • SiteDetail(array)
      • 0(array)
        • id1341
        • application_id1197
        • county_id(null)
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        • misc(null)
        • created2022-12-08 14:00:48
        • modified2024-02-15 08:40:56
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id620
        • application_id1197
        • sponsorPrincess Maxima Paediatric Oncology Center
        • sponsor_typeResearch Institution
        • contact_person
        • addressHeidelberglaan 25, 3584 CS Utrecht, Netherlands
        • telephone_number+31889728751
        • fax_number
        • cell_number+31625710324
        • email_addressG.J.L.Kaspers@prinsesmaximacentrum.nl
        • created2022-12-08 14:00:48
        • modified2024-02-15 08:40:56
  • 4(array)
    • Application(array)
      • id1196
      • user_id263
      • trial_status_id4
      • abstract_of_study<p>\n COVID-19 pandemic has caused global suffering, mortality, and severe economic pressures. New variants of SARS-CoV-2 have been identified some of which increase the load of virus shed from an infected person, resulting in an increase in viral transmission and potentially severity of illness. There is no proven COVID-19 treatment for people who are not sick enough to be hospitalized. There is an urgent need to rapidly assess treatments in an outpatient setting, to prevent disease progression, and reduce serious complications or death. This trial will be a Phase-3, multi-center, randomized, double-blind, to evaluate safety and efficacy of S-217622 versus placebo among a global sample of approximately 1490 (745 on S-217622 and 745 on placebo) will be randomized into the study. Outpatient adults ( ≥ 18 years) with: a) documented positive SARS-CoV-2 nucleic acid or antigen test from a sample collected ≤120 hours (5 days) prior to randomization, b) onset of symptoms of COVID-19 ≤ 5 days prior to randomization, c) presence of 1 or more select COVID-19 symptoms within 24 hours prior to randomization. Participants will be eligible regardless of vaccination status and will be classified as either high risk or low risk. High-risk participants: defined as aged ≥65 years or those with presence of highrisk conditions. Low-risk participants: defined as those not meeting the high-risk definition. We target to initially enrol about 100 participants, but this will depend on how quickly the enrolment target is reached across all sites. Participants will be randomized into the study using an IRT, and stratified by geographic region, regardless of COVID-19 vaccination status. Participants’ demographics will be collected, medical history and physical examination done, vital signs and lab tests conducted as well as adverse events reported. The main intent of the ACTIV-2d/A5407 study is to evaluate the efficacy of S-217622 vs. placebo. The study will be conducted in the setting of locally available standard of care COVID-19 treatment. High-risk and low-risk participants will be analyzed together for the primary analysis and separately for secondary analyses. There will be safety analyses, which will be analyzed in the Safety population, and pharmacokinetic (PK) analyses, which will be analyzed in the PK population. The study duration will be from days 1 through 29 intensive study, followed by limited study through 24 weeks. </p>\n
      • study_title<p>\n A Phase 3, multicenter, randomized, double-blind, 24-week study of the clinical and antiviral effect of S-217622 compared with placebo in non-hospitalized participants with COVID-19</p>\n
      • laymans_summary<p>\n The COVID-19 outbreak in the human population was first reported in Wuhan City, Hubei Province, China in December 2019. The rapid increase in the number of cases led to a declaration by the World Health Organization (WHO) on 11 March 2020 that the disease had spread to the whole world. As of May 2, 2021, the virus had been detected in more than 200 countries and infected more than 151 million people, causing more than 3.1 million deaths worldwide. In Kenya, as of May 10, 2021, more than 163 thousand cases and over 2,900 deaths had been reported. The signs and symptoms of COVID-19 presents differently in people. In the majority of people who are infected, it is mild, or the person may not have any symptoms of sickness. However, among patients with symptoms, typical presentations include fever, cough, muscle aches and shortness of breath. More severe cases have difficulty in breathing requiring admission in a hospital and this results in death in some patients. For majority of people, it does not require treatment but symptoms such as tiredness and shortness of breath appear to persist up to 2 months even after the virus has cleared. Several vaccines against COVID-19 have become available for use, and vaccinations have been initiated in many countries for the older people and the ones at high risk like doctors and nurses. These vaccines appear to be effective in preventing COVID-19 but we currently don’t know if the vaccines will work well long-term. In many middle- or low-income countries like Kenya, there is a shortage in the supply of these vaccines and this is expected to remain the case well beyond 2021. Some treatment options like steroids for patients with severe disease requiring admission in hospital have become available. Still, new treatments that can be given early after infection to prevent disease progression and long-term complications are urgently needed. Recent studies show that the treatments are beneficial in patients treated within the first 7 days after symptoms starts, reducing the need for subsequent hospital and doct</p>\n
      • short_titleACTIV-2d/A5407
      • protocol_noECCT/23/01/04
      • version_noACTIV-2d/A5407 Version 3.0 23 Jun 2022
      • date_of_protocol30-06-2022
      • study_drugS-217622
      • disease_condition (SARS-CoV-2) Infection
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameS-217622
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
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      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist0
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantElizabeth Chirchir
      • declaration_date124-01-2023
      • declaration_principal_investigatorDr Lucas Tina
      • declaration_date224-01-2023
      • placebo_presentYes
      • study_objectives<p>\n <strong>1. STUDY OBJECTIVES</strong></p>\n<p>\n The main intent of the study is to evaluate the efficacy of S-217622 vs. placebo. The study will be conducted in the setting of locally available standard of care COVID-19 treatment. High-risk and low-risk participants will be analyzed together for the primary analysis and separately for secondary analyses. The following primary, secondary, and exploratory objectives will be addressed in the modified intent-to-treat (mITT) population, except for the safety analyses, which will be analyzed in the Safety population, and pharmacokinetic (PK) analyses, which will be analyzed in the PK population</p>\n<p>\n <strong>1.1. Primary Objective</strong></p>\n<p>\n To determine if S-217622 will reduce the time to sustained symptom resolution through Day 29. Time to sustained symptom resolution is defined as the time from start of study intervention to the first day of 4 consecutive days with complete resolution of 13 COVID-19 symptoms on participant self-assessment AND alive and without hospitalization for any reason by Day 29. Hospitalization is defined as ≥24 hours of acute care, in a hospital or similar acute care facility, including emergency rooms, urgent care clinics, or facilities instituted to address medical needs of those with COVID-19.</p>\n<p>\n <strong>1.2. Secondary Objectives </strong><br />\n 1.2.1. Key secondary objective: To determine the effect of S-217622 compared with placebo on the change from baseline in quantitative log10 SARS-CoV-2 RNA levels by PCR on NP swab at Day 4.</p>\n<p>\n 1.2.2. Key secondary objective: To determine whether S-217622 reduces COVID-19- related hospitalization (adjudicated) and all deaths regardless of occurrence outside of hospital or during hospitalization (not adjudicated) through Day 29.</p>\n<p>\n 1.2.3. To determine if S-217622 will decrease the proportion of participants with detectable SARS-CoV-2 viral culture on NP swab at Day 4.</p>\n<p>\n 1.2.4. To explore differences between S-217622 and placebo in time to sustained symptom resolution through Day 29 among subgroups, including by high risk vs. low risk at enrollment, by COVID-19 vaccination status, by receipt of COVID-19 treatments, and by time from symptom onset at enrollment.</p>\n<p>\n 1.2.5. To explore differences between S-217622 and placebo in the proportion of participants with detectable SARS-CoV-2 by viral culture from NP swab at Day 4 among subgroups, including by high risk vs. low risk at enrollment, by COVID-19 vaccination status, by receipt of COVID-19 treatments, and by time from symptom onset at enrollment.</p>\n<p>\n 1.2.6. To determine whether S-217622 reduces all-cause hospitalization and all deaths regardless of occurring prior to hospitalization (not adjudicated) through Day 29.</p>\n<p>\n 1.2.7. To determine if S-217622 will decrease the proportion of participants with detectable SARS-CoV-2 by viral culture from NP swab at Day 8.</p>\n<p>\n 1.2.8. To determine the efficacy of S-217622 to increase the proportion of participants with NP SARS-CoV-2 RNA levels by quantitative polymerase chain reaction (PCR) below the lower limit of quantification (LLoQ) on Days 4 and 8.</p>\n<p>\n 1.2.9. To determine whether S-217622 reduces levels of SARS-CoV-2 RNA by quantitative PCR in NP swabs from participants on Days 4 and 8.</p>\n<p>\n 1.2.10. To determine whether S-217622 results in a shorter time to return to pre-COVID-19 health compared with placebo throughDay 29.</p>\n<p>\n 1.2.11. To evaluate the efficacy of S-217622 compared with placebo based on the assessment of symptoms using the World Health Organization (WHO) ordinal scale (1-8) (see Section 6.3.16).</p>\n<p>\n 1.2.12. To determine the efficacy of S-217622 to maintain pulse oximetry measurement of ≥96% through Day 29.</p>\n<p>\n 1.2.13. To evaluate the safety of S-217622.</p>\n<p>\n 1.2.14. To explore measures of psychological health, functional health, and health-related quality of life in participants through end of study follow-up (Week 24). 1.2.15. To determine whether S-217622 reduces death due to any cause through end of study follow-up (Week 24).</p>\n<p>\n 1.2.16. To determine the PK of S-217622.</p>\n<p>\n <strong>1.3. Exploratory Objectives</strong></p>\n<p>\n 1.3.1. To evaluate whether S-217622 reduces a COVID-19 Severity Ranking Scale score based on COVID-19-associated symptom burden (severity and duration), hospitalization, and death through Day 29.</p>\n<p>\n 1.3.2. To explore the impact of S-217622 on participant-reported rates of new SARS-CoV-2 positivity of household contacts through Day 29.</p>\n<p>\n 1.3.3. To explore whether baseline and follow-up laboratory markers are associated with clinical and virologic outcomes in relation to S-217622 use.</p>\n<p>\n 1.3.4. To explore baseline and emergent viral resistance to S-217622 through Day 16.</p>\n<p>\n 1.3.5. To explore differences between S-217622 and placebo in NP SARS-CoV-2 RNA levels among subgroups, including by high risk vs. low risk at enrollment, by COVID-19 vaccination status, by receipt of COVID-19 treatments, and by time from symptom onset at enrollment</p>\n<p>\n 1.3.6. To explore possible predictors of outcomes, including death and hospitalization, across the study population, including by time from symptom onset, symptoms at baseline, sex assigned at birth, demographic characteristics, geographic region, and vaccination status.</p>\n<p>\n 1.3.7. To explore and develop a model for the interrelationships between virologic outcomes and clinical outcomes in each study group.</p>\n<p>\n 1.3.8. To explore the association between viral genotypes and phenotypic susceptibility to S-217622 and clinical outcomes and virologic response to S-217622. 1.3.9. To explore the prevalence, severity, and types of persistent symptoms and clinical sequelae in participants through end-of-study follow-up (Week 24).</p>\n<p>\n 1.3.10. To explore relationships between exposure of S-217622 with laboratory markers and clinical outcomes.</p>\n<p>\n 1.3.11. To evaluate the safety of S-217622 in the high-risk and low-risk subpopulations. 1.3.12. To explore differences between S-217622 and placebo in death due to any cause through end of study follow-up (Week 24) in the high-risk and low-risk subpopulations.</p>\n<p>\n 1.3.13. To explore the frequency of symptomatic viral rebound, defined as an increase in quantitative NP SARS-CoV-2 viral culture or NP SARS-CoV-2 RNA levels by quantitative PCR after Day 4 in the setting of new or worsening clinical symptoms, in both study groups.</p>\n<p>\n 1.3.14. To explore the frequency of viral rebound in both treatment arms, defined as an increase in quantitative NP SARS-CoV-2 viral culture or NP SARS-CoV-2 RNA levels by quantitative PCR after Day 4.</p>\n<p>\n 1.3.15. To explore differences between S-217622 and placebo to reduce levels of SARS-CoV-2 RNA by quantitative PCR in NP swabs from participants on Days 4 and 8 among participants who have a positive culture at baseline</p>\n
      • principal_inclusion_criteria<p>\n <strong>Inclusion Criteria</strong></p>\n<p>\n <strong>For all participants</strong></p>\n<ol>\n <li>\n Ability and willingness of participant to provide informed consent prior to initiation of any study procedures.</li>\n <li>\n  Age ≥18 years.</li>\n <li>\n  Documentation of laboratory-confirmed active SARS-CoV-2 infection, as determined by a nucleic acid (e.g., reverse-transcriptase PCR) or antigen test from any respiratory tract specimen (e.g., oropharyngeal, NP or nasal swab, or saliva) collected ≤120 hours (5 days) prior to randomization.</li>\n <li>\n  Participants are expected to begin study intervention ≤5 days from self-reported date of onset of any of the COVID-19-related symptoms from the following list: ï‚· Cough ï‚· Shortness of breath or difficulty breathing ï‚· Feeling feverish ï‚· Chills ï‚· Fatigue ï‚· Body pain or muscle pain or aches ï‚· Diarrhea ï‚· Nausea ï‚· Vomiting ï‚· Headache ï‚· Sore throat ï‚· Nasal obstruction or congestion ï‚· Nasal discharge ï‚· Loss of taste or smell</li>\n <li>\n  One or more of the following signs/symptoms present within 24 hours prior to randomization (all criteria in Section</li>\n <li>\n  except loss of taste or smell): ï‚· Cough ï‚· Shortness of breath or difficulty breathing ï‚· Feeling feverishï‚· Chills ï‚· Fatigue ï‚· Body pain or muscle pain or aches ï‚· Diarrhea ï‚· Nausea ï‚· Vomiting ï‚· Headache ï‚· Sore throat ï‚· Nasal obstruction or congestion ï‚· Nasal discharge</li>\n <li>\n  Oxygenation saturation of ≥92% on room air adjusted for altitude and obtained at rest by study staff within 24 hours prior to randomization. (See Manual of Procedures [MOP] for details of adjustments for altitude.) NOTE: For a potential participant who regularly receives chronic supplementary oxygen for an underlying lung condition, oxygen saturation measured while on their standard home oxygen supplementation level must be ≥92%.</li>\n <li>\n Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period unless meeting hospitalization criteria or reaching Day 29, whichever is earliest.</li>\n <li>\n For participants who are of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to randomization. Reproductive potential is defined as: ï‚· Participants who have reached menarche ï‚· Participants who have not been postmenopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH level is not available ï‚· Participants who have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or bilateral salpingectomy) Note: For individuals with permanent infertility due to an alternate medical cause (e.g., Mullerian agenesis, androgen insensitivity), investigator discretion should be applied to determining study entry and need for pregnancy testing.</li>\n <li>\n Participants who are of reproductive potential who engage in sexual activity that may lead to pregnancy must agree to use effective contraception from study entry through 14 days after the last dose of study intervention. Effective methods of contraception include Sexual abstinence ï‚· Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (e.g., oral, intravaginal, transdermal, injectable) PLUS an additional barrier method ï‚· Progestogen-only hormone contraceptive associated with inhibition of ovulation: oral, injectable PLUS an additional barrier method ï‚· Implanted progestogen-only contraceptives associated with inhibition of ovulation PLUS an additional barrier method ï‚· Intrauterine devices (with or without release of hormones) ï‚· Bilateral tubal occlusion (e.g., bilateral tubal ligation) ï‚· Vasectomized partner ï‚· Barrier methods that include male or female condom (cervical cap, diaphragm or sponge with spermicide) The investigator, in consultation with the participant, will confirm that the participant has selected an appropriate method of contraception. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy. NOTE: Participants not of reproductive potential are eligible without requiring the use of a contraceptive method. Participant-reported history is acceptable documentation of surgical sterilization and menopause, including vasectomy in a sole partner.</li>\n <li>\n  Participants assigned female sex at birth who are of reproductive potential must agree not to donate eggs (ova, oocytes) for the purpose of reproduction from study entry through 14 days after the last dose of S-217622 or placebo.</li>\n <li>\n  Participants with pregnant partners must agree to use condoms during vaginal intercourse from study entry through 14 days after the last dose of S-217622 or placebo administration. NOTE: Participants are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives (as described in Section 4.1.1.9) from study entry through 14 days after the last dose of study intervention is administered.</li>\n <li>\n Participants assigned male sex at birth must agree to refrain from sperm donation from study entry through 14 days after the last dose of S-217622/placebo administration.</li>\n <li>\n Participant is willing and able to comply with the study requirements and procedures as judged by the investigator.                                                           <strong>For high-risk participants (limited to 50% of enrollment</strong></li>\n <li>\n Participants at high risk are defined as having 1 or more factors that lead to a higher risk of progression to severe COVID-19: ï‚· Age ≥65 years ï‚· Age ≥18 with 1 of the following: o Obesity (body mass index [BMI] ≥30 kg/m2 ). Note: BMI is rounded to the nearest whole number, for example 29.5 kg/m2 is rounded to 30 kg/m2 . o Diabetes mellitus o Hypertension o Cardiovascular disease (including congenital heart disease) o Chronic lung disease (e.g., chronic obstructive pulmonary disease [COPD], moderate to severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension) o Chronic kidney disease, as long as the participant does not have known creatinine clearance (CrCl) <30 mL/min by Cockcroft-Gault or require dialysis (see Exclusion Criterion 4.1.2.9) o Down syndrome o Sickle cell disease o One of the following immunocompromising conditions or immunosuppressive treatments:  Receiving chemotherapy or other therapies for cancer  Hematologic malignancy (active or in remission)  History of a hematopoietic stem cell or a solid organ transplant  HIV infection: not on antiretroviral therapy or with CD4+ cell count <200 cells/mm3  Combined primary immunodeficiency disorder  Taking immunosuppressive medications (e.g., drugs to suppress rejection of transplanted organs or to treat rheumatologic and gastrointestinal conditions, such as anti-TNF agents, mycophenolate, and rituximab) Note: Current use of some corticosteroids is exclusionary, due to concern for possible DDI with S-217622. See Section 5.4.2 for prohibited medications</li>\n</ol>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p>\n <strong>Exclusion Criteria</strong></p>\n<ol>\n <li>\n  History of hospitalization for the current SARS-CoV-2 infection (i.e., prior hospitalization for a prior episode of SARS-CoV-2 infection is allowable).</li>\n <li>\n  For the current SARS-CoV-2 infection, any positive SARS-CoV-2 molecular (nucleic acid) or antigen test from any respiratory tract specimen (e.g., oropharyngeal, NP or nasal swab, or saliva) collected ˃120 hours (5 days) prior to randomization. Participants with reinfection, defined as prior SARS-CoV-2 infection that began >90 days prior to the current onset of symptoms with interval resolution of symptoms are eligible as long as the current infection has not been present for more than 5 days prior to randomization.</li>\n <li>\n  Current need for hospitalization or immediate medical attention in the opinion of the investigator.</li>\n <li>\n Current use of any medications prohibited with the study intervention, as described in Section 5.4.2. Use of Paxlovid at any time and the use of any oral, inhaled, or injectable medication intended to treat symptomatic SARS-CoV-2 infection before enrollment are excluded. After enrollment, locally available SARS-CoV-2 treatment (including but not limited to molnupiravir, mAbs, outpatient IV remdesivir, convalescent plasma, inhaled budesonide, favipiravir, and fluvoxamine) will be permitted, as long as there are no concerns for DDIs as outlined in Section</li>\n <li>\n Receipt of any investigational treatments for the current episode of SARS-CoV-2 at any time prior to randomization is exclusionary. NOTE: This does not include drugs approved for other uses and taken for those indications or COVID-19 vaccines. NOTE: Use of locally authorized or approved therapies to prevent COVID-19, such as mAbs given solely to prevent COVID-19, are not exclusionary.</li>\n <li>\n Any comorbidity requiring surgery within 7 days prior to randomization or that is considered life threatening in the opinion of the investigator within 28 days prior to randomization.</li>\n <li>\n Currently pregnant or breastfeeding.</li>\n <li>\n  Known allergy/sensitivity or any hypersensitivity to components of S-217622 or placebo for S-217622.</li>\n <li>\n  Known current renal impairment defined as CrCl <30 mL/min by Cockcroft-Gault or requiring dialysis.</li>\n <li>\n  Known history of cirrhosis or liver decompensation (including ascites, variceal bleeding, or hepatic encephalopathy)</li>\n <li>\n  Participants who have used any of the following drugs within 14 days prior to enrollment: – Strong CYP3A inducer – Products containing St. John's Wort</li>\n</ol>\n
      • primary_end_points<p>\n The primary outcome measure is: Time in days from the start of S-217622 to sustained symptom resolution; the definition of sustained symptom resolution is the first of 4 consecutive days without symptoms (all targeted symptoms recorded as absent) and being alive and without hospitalization for any reason by Day 29. </p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
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      • scope_pharmacodynamic0
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      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p style=\"margin-left:18.0pt;\">\n <u><strong>SITE -714_ MOI UNIVERSITY CLINICAL RESEARCH CENTRE_Prof Abraham Siika</strong></u></p>\n<p style=\"margin-left:18.0pt;\">\n <u><strong>Study area</strong></u></p>\n<p style=\"margin-left:18.0pt;\">\n In 2004, the Moi University Clinical Research Centre (MUCRC) was founded as an international site of the Indiana University AIDS Clinical Trials Unit (ACTU), an affiliate of the AIDS Clinical Trials Group (ACTG) Network. Following two years of site preparation, trial A5208/OCTANE (Optimal Combination Therapy after Nevirapine Exposure) was initiated at the MUCRC in July 2006.In December 2006, Indiana University was defunded from the ACTG Network and the MUCRC reverted to the Division of AIDS (DAIDS) of the National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), as a protocol-limited site. In December 2008, MUCRC became a site for the United States Military HIV Research Program (USMHRP) and continues to perform clinical trials for the ACTG Network.</p>\n<p style=\"margin-left:18.0pt;\">\n While MUCRC is a clinical trials site for the USMHRP, it operates under the auspices of the USAID – Academic Model Providing Access to Healthcare Research Network (AMPATH ResNet). AMPATH, founded in November 2001, is a collaboration between the Moi University School of Medicine (MUSoM), Moi Teaching and Referral Hospital (MTRH) and a network of North American Medical Schools (the AMPATH Consortium) led by Indiana University School of Medicine (IUSoM).</p>\n<p style=\"margin-left:18.0pt;\">\n <u><strong>Location </strong></u></p>\n<p style=\"margin-left:18.0pt;\">\n The MUCRC is located on the second floor of the Chandaria Cancer and Chronic Diseases Centre, Eldoret, Kenya. The CRS has the following areas/rooms: a waiting bay for patients; a nursing station (for consenting, vital signs measurements); a phlebotomy room; four clinical examination rooms; a pharmacy (including a separate cyctoxics preparation room) one data room; one office for the site coordinator, study coordinators and regulatory affairs officer. one office for quality assurance/control officer, the pharmacist room, recruiters room, a staff recreational room; and separate toilets for staff and patients.</p>\n<p style=\"margin-left:18.0pt;\">\n <u><strong>Staffing</strong></u></p>\n<p style=\"margin-left:18.0pt;\">\n MUCRC has a total of 9 Investigators-Prof Abraham Mosigisi Siika, MBChB, MMed, Dr Charles Kwoba, MBChB, MMed, MSc,one Pharmacist-,Natalie Sang, Bpharm one backup associate pharmacist, three backup Pharmacy technologist; one Site Manager; two Study Coordinators;- Viola Cherotich Kirui, BSc,Susan Wanjiru nyambura and Arthur Ogendo ,one Regulatory Affairs Officer;Florence Kiwunja Njulu   BSc (EVH)- two QA/QC officer;- two Medical Officers;-Terry Jamatia Tarus, MBChB andHilda Chevera Kaziga, MBChB,six Clinical-Officers -Jairus Kipyego, MPH, BSc, Dip Clinical Medicine & Surgery,Vincent Kipchirchir, Dip Clinical Medicine & Surgery,Viola Samoei, Dip Clinical Medicine & Surgery,Tom Oyoo Osoro, Dip Clinical Medicine & Surgery,Clinton Otieno Achida, Dip Clinical Medicine & Surgery, Getruth Jerop Kiptoo, Dip Clinical Medicine & Surgery,one Data Manager;-Martha Bisieri Mokaya, BSc, MSc,three Assistant Data Managers;-Wilson Lokitala Ekiru, BSc,Ruth Bosire,Cornelius Chege one Phlebotomist; one Laboratory Manager;-Ronald Kibet Tonui, MBChB, MSc. five study nurses-Chris Sande Mboya, Joan Kotut ,Kevin Kipchumba Sang,Eunice Jepkemboi,Philemon Kipchirchir Mutai and eight Recruiters-Cecilia Chebet Mengich,Julie Chepchumba Choge,Amina Msuo Shali,Dorcas Akinyi Opot,Solomon Kimurgor Ngetich,Evans Ochieng Ouno,Shauri Gona and Richard Kipsang Kirui.</p>\n<p style=\"margin-left:18.0pt;\">\n <u><strong>SITE-715-VICTORIA BIOMEDICAL RESEARCH INSTITUTE_Dr Lucas Tina</strong></u></p>\n<p>\n <strong><u>Study area</u></strong></p>\n<p>\n Victoria Biomedical Research Institute(VIBRI) was formed in September 2020 in Kenya, VIBRI’s goal is to accelerate the translation of promising innovations from the laboratory bench to the clinic in the community. The institute provides a dynamic platform for global health research, training and education by bringing together knowledge and resources to address the most important global health issues relevant to Africa.</p>\n<p>\n Working in collaboration with global health partners, VIBRI is committed to the pursuit of knowledge, discovery and clinical development of public health interventions that have a major impact on global health in Africa.</p>\n<p>\n <strong><u>Location</u></strong></p>\n<p>\n VIBRI Clinical Research Centre(CRC) is currently located at Kisumu County Referral Hospital, Kisumu Kenya. The CRC has the following areas/rooms: a waiting bay for patients; a nursing station (for consenting, vital signs measurements); a phlebotomy room; Six clinical examination rooms; a research pharmacy, data room, archival area, admin office for the Project Manager, HR, Finance, admin, Procurement, Investigators and Study Coordinator and separate toilets for staff and patients.</p>\n<p>\n <strong><u>Staffing</u></strong></p>\n<p>\n VIBRI has a total of about 50 Staff. The table below gives more details of the number of staff per department</p>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:506px;\" width=\"506\">\n <tbody>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:64px;height:25px;\">\n <p>\n <strong>Victoria Biomedical Research Institute</strong></p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:205px;height:25px;\">\n  </td>\n <td nowrap=\"nowrap\" style=\"width:237px;height:25px;\">\n  </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n  </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n <strong>Name</strong></p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n <strong>Job Title</strong></p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 1</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Tina, Lucas Otieno</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Principal Investigator and Director</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 2</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Otieno Walter</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 3</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Oketch Dismas</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 4</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nyongesa Henry</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 5</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Lanoi Grace</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 6</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Elizabeth Oele</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 7</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Fredrick Oluoch</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 8</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Odhiambo Diana</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 9</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Oindo, Antony Ochieng</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 10</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Kenson Kipchumba, Nyolmo</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n CO-Investigator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 11</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Odhiambo, Fredrick  Otieno</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Finance Manager</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 12</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Ogolla, David Owino</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Project Manager</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 13</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Miruka, Millicent Melanie</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Research Pharmacist</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 14</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Omollo, Sharon Awuor</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Supply Chain Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 15</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Okuba, Brenda Amollo</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Study Coordinator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 16</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Tom Nyamira</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Lab Coordinator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 17</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Onyamasi, Annet Imojong</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Study Nurse</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 18</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Oyola, Eunice Awuor</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Clinical Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 19</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Otitah, Lydiah Akinyi</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Data Entry Clerk</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 20</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Owuor, Josephine Akinyi</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Administrative Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 21</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Omollo, Vincent Omondi</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Lab Coordinator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 22</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Olado, Geoffrey Oduasi</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Study Coordinator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 23</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Wamboga, Serphine Achieng</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Field Assistant</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 24</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Oduol, Edith Aluoch</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Field Assistant</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 25</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Oduol, Franciscah Awino</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Field Assistant</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 26</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Otieno, Alfred Ochieng</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Data Entry Clerk</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 27</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Onyango, Mary Immaculate</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n HR Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 28</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Osodo, Paul Mwita</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n HIV Testing Services Pro</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 29</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Opiyo, Maurice Otieno</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Field Coordinator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 30</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nyagol, Beatrice Achieng</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Clinical Research Coordinator</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 31</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nyauke, Gaudensia</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nursing Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 32</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Oriato, Jane Atieno</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nursing Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 33</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Pande, Nickanor Odiwuor</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Lab Technologist</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 34</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Ongito, Ann Rogena</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Pharmacist</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 35</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Okello, Leah Martha</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Clinical Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 36</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Agengo, David</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Lab Technologist</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 37</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Jode, Akinyi Rose</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Office Assistant</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 38</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Adera, Irene Akinyi</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nursing Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 39</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Orimbo, Roseline Awuor</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nursing Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 40</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Awino, George Odhiambo</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nursing Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 41</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Ojwang, George Gome</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Clinical Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 42</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Odhach, Finch Awuor</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Clinical Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 43</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Omondi, Felix Oyoo</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Data Manager/IT Consulta</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 44</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Immaculate Achieng, Ochieng</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nursing Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 45</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Mercy Atieno, Opondo</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Data Entry Clerk</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 46</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Samson, Ndori</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Data Entry Clerk</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 47</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Okatch, Pinto Otieno</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Lab Technologist</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 48</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Otieno, Ezekiel Onditi</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Field Assistant</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 49</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n John, Mercy Akinyi</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Nursing Officer</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p align=\"right\">\n 50</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n Linda Okuba</p>\n </td>\n <td nowrap=\"nowrap\" style=\"height:19px;\">\n <p>\n QC</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:18.0pt;\">\n  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n Medicines Control Authority of Zimbabwe-20 Jan 2023</p>\n<p>\n National Drug Authority-Uganda_29 Oct 2022</p>\n<p>\n Medical Research commitee Department of health-United Arab Emirates-24 Nov 2022</p>\n
      • other_details_regulatory_approved<p>\n Not Applicable</p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration24 weeks
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites6
      • multi_country_listNorth America, South America, Europe, Africa, and Asia
      • data_monitoring_committeeYes
      • total_enrolment_per_site15 Participants
      • total_participants_worldwide1490 Participants
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameLucas
      • investigator1_middle_nameTina
      • investigator1_family_nameOtieno
      • investigator1_qualificationBachelor of Medicine and Surgery (MBChB)
      • investigator1_professional_addressVictoria Biomedical Research Institute (VIBRI)
      • investigator1_telephone+254720597654
      • investigator1_emailltina@vibriafrica.org
      • organisations_transferred_Yes
      • number_participantsWe expect that approximately 90 participants, aged between 18 and ≥80 years, will be participating, from 6 sites in Kenya.
      • notification<p>\n There are 6 sites participating in the study.Currently 1 site has received LEC(Amref)Approval,the remaining 5 sites are still under review with EC.We will send the approval letters and other essential documents once available.</p>\n
      • approval_date01-06-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-01-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed
      • final_report
      • implication_results
      • quantity_imported6
      • quantity_dispensed0
      • quantity_destroyed0
      • quantity_exported6
      • balance_site0
      • final_date0000-00-00
      • modified2025-03-07 14:33:46
      • created2022-12-05 15:23:22
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id870
        • application_id1196
        • given_nameLucas
        • middle_nameTina
        • family_nameOtieno
        • qualificationBachelor of Medicine and Surgery (MBChB)
        • professional_addressVictoria Biomedical Research Institute (VIBRI)
        • telephone+254720597654
        • emailltina@vibriafrica.org
        • created2022-12-05 15:35:12
        • modified2023-01-25 11:49:21
    • SiteDetail(array)
      • 0(array)
        • id1340
        • application_id1196
        • county_id27
        • site_nameMOI UNIVERSITY CLINICAL RESEARCH CENTRE
        • physical_addressCHANDARIA CANCER AND CHRONIC CENTRE AT MOI TEACHING AND REFERRAL HOSPITAL
        • contact_detailsP.O BOX 4606,3010-ELDORET KENYA
        • contact_personProf Abraham Mosigisi Siika
        • site_capacity(null)
        • misc(null)
        • created2022-12-05 15:35:12
        • modified2023-01-25 11:49:21
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 1(array)
        • id1347
        • application_id1196
        • county_id42
        • site_nameVictoria Biomedical Research Institute,
        • physical_addressVictoria Biomedical Research Institute-Kisumu
        • contact_details P.O. Box 7180, Postal Code 40100
        • contact_personDr Lucas Tina
        • site_capacity(null)
        • misc(null)
        • created2023-01-09 14:06:33
        • modified2023-01-25 11:49:21
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1414
        • application_id1196
        • county_id35
        • site_name Kenya Medical Research Institute/Walter Reed Project
        • physical_addressHospital Road, Kericho, Kenya
        • contact_detailsP.O Box 1357 – 20200,
        • contact_personDr. Lucy C. Koech
        • site_capacity(null)
        • misc(null)
        • created2023-01-23 15:43:24
        • modified2023-01-25 11:49:21
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
      • 3(array)
        • id1415
        • application_id1196
        • county_id47
        • site_name Kenyatta National Hospital
        • physical_addressKenyatta National Hospital
        • contact_detailsP.O. Box 20723-00202
        • contact_personDr John Kinuthia
        • site_capacity(null)
        • misc(null)
        • created2023-01-23 15:43:24
        • modified2023-01-25 11:49:21
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 4(array)
        • id1416
        • application_id1196
        • county_id42
        • site_nameAhero Clinical Trials Unit,
        • physical_addressAhero County Hospital,
        • contact_detailsP.O. Box 54-40100
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2023-01-23 15:43:24
        • modified2023-01-25 11:49:21
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 5(array)
        • id1417
        • application_id1196
        • county_id37
        • site_nameKEMRI CCR – BUTERE SITE
        • physical_addressBUTERE COUNTY HOSPITAL
        • contact_detailsP.O. Box 40-50101
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2023-01-23 15:43:24
        • modified2023-01-25 11:49:21
        • County(array)
          • id37
          • county_nameKakamega
          • created2012-06-15 10:26:29
          • modified2012-06-15 10:26:29
    • Sponsor(array)
      • 0(array)
        • id619
        • application_id1196
        • sponsorShionogi*
        • sponsor_typeIndustry
        • contact_personShionogi Pharma Co Ltd Seetsu Plant
        • addressShionogi & Co., Ltd. 1-8, Doshomachi 3-chome, Chuo-ku, Osaka 541-0045 Japan
        • telephone_number+81-6-66382-7341
        • fax_number
        • cell_number+81-6-66382-7341
        • email_addresssimon.portsmouth@shionogi.com
        • created2022-12-05 15:35:12
        • modified2023-01-25 11:49:21
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • approved2
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php