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  • trial_therapeutic_confirmatory1

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  • 1Recruiting
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• applications(array)
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    • Application(array)
      • id1328
      • user_id747
      • trial_status_id(null)
      • abstract_of_study<p>\n Sickle cell disease (SCD) is a rare, devastating, and debilitating disease marked by the pathophysiologic features of hemolytic anemia, vaso-occlusion, and progressive end-organ damage, with a clinical course characterized by life-long disability and early death.As current treatment options are limited, there remains a significant unmet medical need for novel therapies and for the early treatment of pediatric patients with SCD to mitigate the consequences of the disease.</p>\n<p>\n Voxelotor (formerly known as GBT440) is an orally administered small molecule that inhibits HbS polymerization by allosterically modifying hemoglobin-oxygen (Hb-O2) affinity. It is approved in the United States for the treatment of SCD in adults and pediatric patients 4 years of age and older. By inhibiting HbS polymerization, voxelotor has been shown to improve RBC deformability and reduce blood viscosity. Treatment with voxelotor has also led to significant reductions in sickle cell counts in the peripheral blood, which supports the potential for voxelotor to serve as a disease-modifying therapy for SCD.</p>\n<p>\n The objective of this OLE is to assess the safety of, and SCD-related complications with, long-term treatment with voxelotor in participants who have completed treatment in a GBT-sponsored voxelotor clinical study, based on the following parameters: 1. Adverse events (AEs), clinical laboratory tests, physical examinations (PEs), and other clinical measures 2.Frequency of SCD-related complications</p>\n<p>\n This multicenter, nonrandomized OLE will be conducted globally and will be available to eligible participants from GBT-sponsored voxelotor clinical studies. Participants must have completed participation in their originating clinical study and must meet the entry criteria for this study to be eligible for enrollment. The study will be conducted at up to approximately 70 global clinical sites, and up to approximately 600 participants will be enrolled. All participants will receive voxelotor QD, administered orally as tablets, dispersible tablets, or a powder for oral suspension dosage form (packaged as stick packs). Participants aged ≥ 12 years will receive a voxelotor dose of 1500 mg QD. Participants aged < 12 years will receive a voxelotor dose based on their body weight, to provide exposure corresponding to the adult dose of 1500 mg QD. Participants may receive the study drug as long as receive clinical benefit that outweighs risk as determined by the Investigator for a minimum of 96 weeks and/or until they have access to voxelotor from an alternative source (e.g., through commercialization or a managed access program) and will end when the last participant’s last visit occurs.</p>\n<p>\n Statistical programming and analyses will be performed using established statistical methods. Study data will be reported using summary tables, figures, and select data listings. Continuous variables will be summarized using mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarized by presenting the number (frequency) and percentage in each category. All statistical analyses conducted will be descriptive and no formal statistical tests are planned. As appropriate, study data may be summarized separately based on the antecedent study.</p>\n<p>\n  </p>\n
      • study_title<p>\n An Open-Label Extension Study of Voxelotor Administered Orally to Participants with Sickle Cell Disease Who Have Participated in Voxelotor Clinical Trials</p>\n<p>\n  </p>\n
      • laymans_summary<p>\n Sickle Cell Disease is an inherited disorder caused by a change in the structure of a DNA sequence that makes part of the protein known as haemoglobin abnormal. Haemoglobin is a compound found within red blood cells (RBCs) that binds oxygen and transport it from the lungs to the rest of the body. RBCs with the abnormal sickle cell haemoglobin do not function normally. They are stiff and when they lose oxygen they form into a shape of a sickle and stick together blocking small blood vessels. This blockage causes pain and breakdown of these cells which results in blood not having enough healthy red blood cells. The only current cure for SCD is a medical treatment where one’s bone marrow is infused with healthy blood-forming cells so as to replace the abnormal sickle cells. It is very expensive and chances of one getting a suitable donor are not high. </p>\n<p>\n There is, therefore, a need for treatments that can help alleviate the complications associated with the disease such as low level of healthy red blood cells and injury to the brain due to low oxygen levels. This study will involve participants with SCD who participated in voxelotor clinical trials. They will be enrolled to continue receiving voxelotor or started on voxelotor if they were receiving the alternative substance that has no effect on the body for comparison. All participants will receive voxelotor once a day in the form of tablets for swallowing, tablets for dissolving in water or a powder added to liquids. Participants who are 12 years old and above take 3 tablets that are 500mg each while those below 12 years will have their dose calculated using their body weight. The study will be conducted in multiple countries and involve approximately 70 global sites, with approximately 600 participants enrolled. Voxelotor presents the potential of been a drug that can be used in the early treatment of patients with sickle cell disease due to its ability to improve the low level of red blood cells by preventing their abnormal breakdown. Identified risks include mild reactions to the medication such as diarrhoea, abdominal pain, nausea, rash, and drug hypersensitivity, which were managed by dose reduction and/or treatment of symptoms without needing to discontinue treatment. Participants will therefore benefit from participating in this study and will be monitored for safety and SCD-related complications. Participants will be in the study for a minimum of 96 weeks and/or until they have access to voxelotor from an alternative source (e.g., through commercialization or a managed access program). The study will end when the last participant’s last visit occurs.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • short_titleGBT440-038Open-Label Extension
      • protocol_noECCT/23/09/04
      • version_noVersion 4.0, Amendment 3
      • date_of_protocol10-08-2022
      • study_drugVoxelotor
      • disease_conditionSickle Cell Disease
      • 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_name2-Hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl) methoxy)benzaldehyde
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressRA@xceneresearch.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_applicantXcene Research Limited
      • declaration_date126-09-2023
      • declaration_principal_investigatorProfessor Jessie Githanga
      • declaration_date226-09-2023
      • placebo_presentNo
      • study_objectives<p>\n The objective of this open-label extension (OLE) is to assess the safety of, and SCD-related complications with, long-term treatment with voxelotor, in participants who have completed treatment in a Global Blood Therapeutics (GBT)-sponsored voxelotor clinical study, based on the following parameters:</p>\n<p>\n • Adverse events (AEs), clinical laboratory tests, physical examinations, and other clinical measures</p>\n<p>\n • Frequency of SCD-related complications</p>\n
      • principal_inclusion_criteria<p>\n Inclusion Criteria</p>\n<p>\n 1. Participants who meet all of the following criteria will be eligible for study enrollment:</p>\n<p>\n 2A. Male or female participant with SCD who participated and received study drug in a GBT-sponsored voxelotor clinical study. Note: Participants who discontinued study drug due to an AE, but who remained on study, may be eligible for treatment in this study provided the AE does not pose a risk for treatment with voxelotor. Note: Participants who discontinued Study GBT440-032 as the result of an abnormal transcranial Doppler (TCD) flow velocity assessment (≥ 200 cm/sec) are eligible for treatment in this study.</p>\n<p>\n 3. Female participants of childbearing potential are required to have a negative urine pregnancy test prior to dosing on Day 1. Note: Female participants who become childbearing during the study must be willing to have a negative urine pregnancy test to remain in the study.</p>\n<p>\n 4. If sexually active, female participants of childbearing potential must use highly effective methods of contraception until 30 days after the last dose of study drug. If sexually active, male participants must use barrier methods of contraception until 30 days after the last dose of study drug.</p>\n<p>\n 5A. Participant has provided written consent/assent (for pediatric participants, both the consent of the participant’s legal representative or legal guardian and the participant’s assent [where applicable] must be obtained).</p>\n
      • principal_exclusion_criteria<p>\n 1. Female participant who is breastfeeding or pregnant</p>\n<p>\n 2A. Participant withdrew consent from a GBT-sponsored voxelotor clinical study</p>\n<p>\n 3A. Participant was lost to follow-up from a GBT-sponsored voxelotor clinical study</p>\n<p>\n 4. Participant has any medical, psychological, safety, or behavioral conditions that, in the opinion of the Investigator, may confound safety interpretation, interfere with compliance, or preclude informed consent</p>\n<p>\n 5. Active symptomatic coronavirus disease of 2019 (COVID-19) infection</p>\n<p>\n 6. Known hypersensitivity to voxelotor or any other components of the study drug</p>\n<p>\n 7. Use of St. John’s wort, sensitive cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic index, or moderate or strong CYP3A4 inducers within 30 days of Day 1</p>\n
      • primary_end_points<p>\n Endpoints:</p>\n<p>\n Safety</p>\n<p>\n •Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)</p>\n<p>\n SCD-Related Complications</p>\n<p>\n • Frequency of SCD-related complications</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyFrequency of Sickle Cell Disease (SCD) Related complications
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Site 11005:</p>\n<p>\n KEMRI-CRDR Nairobi Research Annex:</p>\n<p>\n This facility has clinical rooms available for consenting, nursing procedures and clinical reviews. There are also additional facilities that include an inpatient ward, a pharmacy, a laboratory, staff work stations, a monitoring space and kitchen for preparing participants’ meals. Site staff include the principal investigator, 5 medical officers, 2 pharmacists, 1 pharmaceutical technician, 8 nurses, 8 quality control officers, 10 clinical officers, 4 phlebotomist, 8 laboratory scientists, 4 laboratory technologists, 6 data management officers, 8 administrators and 14 community interviewer.</p>\n<p>\n Site 11001:</p>\n<p>\n KEMRI has a modern research annex at the Siaya County Referral Hospital with capacity to conduct OLE phase studies. Site staff responsible for day to day running of the project include: 1 Medical Officer, 1 Pharmacist, 2 Pharmacy technicians, 6 Nurses, 5 Quality Assurance & Quality Control officers, 2 Clinical Officers, and 7 Community Interviewers, 3 lab personnel, 2 data personnel, 2 administration personnel</p>\n<p>\n Site 11004:</p>\n<p>\n The medical centre is a Strathmore University facility managed in collaboration with the Centre for Research in Therapeutic Sciences (CREATES).  The SUMC study site at Strathmore University will be staffed by CREATES qualified research personnel. The site has a pharmacy, vaccination area, clinical assessment area, data entry area, internal quality control and registration area and space where monitoring can be done. Site staff include: the principal investigator, 3 medical officers, 1 pharmacist, Study co-ordinator among others. </p>\n<p>\n Site 11003:</p>\n<p>\n Gertrude’s Children’s Hospital (GCH) is the largest hospital in East and Central Africa dedicated exclusively to the care of children. For over 60 years, the hospital has provided high standards of paediatric care for children from birth to 21 years of age. The hospital is accredited by the Joint Commission International Accreditation (JCIA) and Safe Care, Netherlands following audits of the hospital facilities. GCH is a non-profit organization, chartered with the responsibility of provision of health services, fostering good health, carrying out research and teaching healthcare professionals. Based in Muthaiga, Nairobi, and spread out to various outpatient clinics all over Nairobi and in several other Counties, the hospital attends to over 300,000 children as outpatients and admits over 6,000 patients on average per year. The over 100-bed hospital offers comprehensive paediatric medical services and there are 21 specialist clinics that cover almost every aspect of paediatric healthcare from haematology, chest conditions, cardiology, dermatology, otorhinolaryngology, endocrinology, oncology and HIV/AIDS. The main hospital in Muthaiga is open 24/7 and offers 24-hour laboratory and pharmacy coverage. Study site staff include: the principal investigator, the co-investigator, the study co-ordinator, study nurses, study pharmacists, logistics manager, Laboratory technician/phlebotomists, QA officers, etc. </p>\n
      • other_details_explanation<p>\n The study is also being conducted in the host country of the applicant / Sponsor. </p>\n
      • other_details_regulatory_notapproved<p>\n The Food and Drugs Authority (FDA) Ghana submitted on the 08th February, 2023</p>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n Regulatory Authorities in Nigeria: National Agency for Food and Drug Administration and Control (NAFDAC) </p>\n<p>\n Date of Approval: 25th October, 2022</p>\n<p>\n Number of sites: 5</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_durationParticipants may receive study drug as long as they continue to receive clinical benefit that outweighs risk as determined by the Investigator and/or until the participant has access to voxelotor from an alternative source (eg, through commercialization)
      • 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_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 (Four)
      • multi_country_listNigeria, Kenya, Ghana, United Kingdom, Lebanon, Saudia Arabia, Egypt, United States of America.
      • data_monitoring_committeeYes
      • total_enrolment_per_sitesite 11001 (5)\nsite 11003 (11)\nsite 11004 (2)\nsite 11005 (6)
      • total_participants_worldwide600
      • 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_consentNo
      • subjects_specify
      • subjects_othersYes
      • subjects_others_specifyChildren (below 12 years) considered as assent.
      • investigator1_given_nameJessie
      • investigator1_middle_nameNyokabi
      • investigator1_family_nameGithanga
      • investigator1_qualificationMBChB, MMed (Path)(UON), FCPath ECSA (Professor)
      • investigator1_professional_address P. O. Box 19601-00202, Nairobi, Kenya
      • investigator1_telephone+254 721245721
      • investigator1_emailjgithanga3@gmail.com
      • organisations_transferred_Yes
      • number_participants24
      • notification<p>\n Not applicable. </p>\n
      • approval_date12-12-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted27-09-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed comprehensively
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-01-17 23:50:57
      • created2023-09-25 17:11:37
      • total_sites(null)
      • ecitizen_invoice(null)
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        • id972
        • application_id1328
        • given_nameJessie
        • middle_nameNyokabi
        • family_nameGithanga
        • qualificationMBChB, MMed (Path)(UON), FCPath ECSA (Professor)
        • professional_address P. O. Box 19601-00202, Nairobi, Kenya
        • telephone+254 721245721
        • emailjgithanga3@gmail.com
        • created2023-09-25 17:14:55
        • modified2023-09-27 10:22:30
      • 1(array)
        • id979
        • application_id1328
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMBchB , MPH, PhD (Professor)
        • professional_addressP.O Box 254, Nairobi, Kenya, Post code 00200
        • telephone(254)- 20-20-2724264/65 (work) (254)-724 —522474(Cell)
        • emailvnduba@gmail.com
        • created2023-09-26 15:49:17
        • modified2023-09-27 10:22:30
      • 2(array)
        • id980
        • application_id1328
        • given_nameBernhards
        • middle_nameRagama
        • family_nameOgutu
        • qualificationMBChB, MMed, PhD
        • professional_addressStrathmore University CREATES Ole Sangale Road, Madaraka Estate P.O BOX 59857-00200 Nairobi, Kenya
        • telephone+254-733-812613
        • emailogutu6@gmail.com
        • created2023-09-26 15:55:01
        • modified2023-09-27 10:22:30
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        • id1596
        • application_id1328
        • county_id47
        • site_nameGertrude’s Children Hospital
        • physical_address34 Muthaiga Road, Off Thika Super Highway, Nairobi, Kenya
        • contact_details(+254)721245721
        • contact_personProf. Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2023-09-25 17:14:55
        • modified2023-09-27 10:22:30
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
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        • id1597
        • application_id1328
        • county_id47
        • site_nameKenya Medical Research Institute (KEMRI), Centre for Respiratory Diseases Research (CRDR)
        • physical_addressKenya Medical Research Institute (KEMRI), Centre for Respiratory Diseases Research (CRDR), Kenyatta National Hospital Off Hospital Road, Nairobi-Kenya
        • contact_detailsP.O Box 47855-00100
        • contact_personProf. Nduba Videlis
        • site_capacity(null)
        • misc(null)
        • created2023-09-26 11:26:34
        • modified2023-09-27 10:22:30
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
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        • id1598
        • application_id1328
        • county_id41
        • site_nameKEMRI CRDR SIAYA within Siaya County Referral Hospital Grounds
        • physical_addressOFF Ugunja Siaya Road
        • contact_details+254700111395 / +254731141831
        • contact_personProf. Nduba Videlis
        • site_capacity(null)
        • misc(null)
        • created2023-09-26 11:35:29
        • modified2023-09-27 10:22:30
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          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
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        • id1599
        • application_id1328
        • county_id47
        • site_nameStrathmore University Medical Center, Centre for Research in Therapeutic Sciences
        • physical_addressOle Sangale road, Madaraka Estate,P.O BOX 59857-00200 Nairobi, Kenya
        • contact_details0795658514/0103318597
        • contact_personDr. Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2023-09-26 11:35:29
        • modified2023-09-27 10:22:30
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id696
        • application_id1328
        • sponsorGlobal Blood Therapeutics, Inc., a wholly owned subsidiary of Pfizer Inc.
        • sponsor_typeIndustry
        • contact_personMark Davis
        • address181 Oyster Point Blvd South San Francisco, CA 94080 United States of America
        • telephone_number925-336-1055 (office)
        • fax_number
        • cell_number925-336-1055 (office)
        • email_addressmdavis1@gbt.com
        • created2023-09-25 17:14:55
        • modified2023-09-27 10:22:30
  • 1(array)
    • Application(array)
      • id1312
      • user_id263
      • trial_status_id4
      • abstract_of_study<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Bifidobacteria are gram-positive, heterofermentative, anaerobic bacteria that colonize the newborn gut within the first days and weeks of life. They are often the most abundant bacterial genus in a breast-fed infant’s intestinal flora. B. infantis metabolizes Human milk oligosaccharides (HMOs) and produces short chain fatty acids (SCFA) that are thought to play an important role in nutrition and immune development, stimulating anti-inflammatory and inhibiting pro-inflammatory responses [Halloran 2019; Henrick 2021].</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n B. infantis Bi-26 strain is a nutritional probiotic intervention that will be evaluated in this trial for its ability to improve weight gain and health outcomes of underweight infants with WAZ <-2 who have been hospitalized with acute illness.</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Clinical study data in the United States (US) have shown that B. infantis strain EVC001 colonizes the gut and is associated with significant changes to fecal microbiome composition in healthy breast-fed infants [Frese 2017; Henrick 2019]. Supplementation of B. infantis EVC001 has been associated with a reduction in pro-inflammatory cytokines [Henrick 2019]. Similar observations have been reported for preterm infants given B. infantis EVC001 [Nguyen 2021].</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n In a pilot trial evaluating B. infantis EVC001 supplementation in Bangladesh in hospitalized 2-to 6-month-old infants with SAM, i.e., weight-for-length z score [WLZ] <-3, researchers observed that daily supplementation with B. infantis for 4 weeks was associated with B. infantis colonization and an increase in WAZ [Barratt 2022].</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A number of B. infantis strains, including Bi-26, have been designated as generally recognized as safe (GRAS) based on review by a panel of independent experts in the field. Furthermore, the US Food and Drug Administration (FDA) did not have questions about the GRAS determination of Bi-26 (GRN 985). In the US, the GRAS determination and the FDA no question letter allow the use of Bi-26 under its intended conditions of use (healthy term infants) in infant formula. The strain bearing the GRAS designation can also be used in dietary supplements, including those for infants.</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n In low-income countries, B. infantis strain Bi-26, evaluated in this study, could potentially be used as a dietary supplement in underweight infants if the safety and efficacy findings of the previous pilot study are confirmed.</div>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A Phase 3, randomized, double-blind, placebo-controlled study to evaluate the effect of Bi-26 (strain of Bifidobacterium longum, B. infantis) supplementation versus placebo on weight gain in underweight infants</span></p>\n
      • laymans_summary<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Poor countries bear a greater burden of children who are born with a weight that is less than it should be for their age. Poor health in the digestive system (gut) can be caused by a poor balance of good bacteria that are thought to play a role in how nutrients are absorbed in the intestines. Good bacteria in a baby’s gut are important in helping the baby grow, develop normally, and be healthier. One of the bacteria, called <em>B. infantis</em>, that is normally found in babies’ guts makes it easier for the baby to digest their mother’s milk and help keep the baby healthy. Babies who have a weight that is less than it should be for their age have less of the <em>B. infantis</em> bacteria, compared to healthy babies. This may cause poor absorption of these nutrients and can lead to babies not being able to gain weight, leading to them becoming underweight and failing to thrive. Providing a dietary supplement with a specific strain of the bacteria known as EVC001 has been shown to boost the friendly bacteria living in the gut and cause significant changes in the composition of the friendly bacteria and its environment in the gut especially in healthy babies who are breastfed. </p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A small study in Bangladesh tested this strain among babies who were aged between 2 and 6 months and had been admitted to hospital, who were also suffering from severe acute malnutrition. They were given the friendly <em>B. infantis</em> bacteria species as a dietary supplement daily for a period of four weeks. It was found out that this supplementation boosted the friendly bacteria and resulted in the children gaining weight and improving their nutritional weight-for-age Z score (WAZ). We want to study underweight babies who are between 1 and 4 months of age who are in the hospital, to see if they will also gain weight after taking the <em>B. infantis </em>supplement Bi-26. If the results in our study show that the dietary supplements with this friendly bacterial species of <em>B. infantis</em> improves weight gain among underweight children, then it can potentially be used in poor countries as a dietary supplement in babies who are underweight.</p>\n
      • short_titleCONSTELLATION
      • protocol_noECCT/23/09/03
      • version_no4.0
      • date_of_protocol12-09-2022
      • study_drugBi-26 (strain of Bifidobacterium longum, B. infantis)
      • disease_conditionInfant malnutrition
      • 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_namePlacebo
      • comparator_registeredN/A
      • comparator_countriesN/A
      • 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_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_applicantFerial Israel
      • declaration_date114-09-2023
      • declaration_principal_investigatorDr Lucas Otieno Tina
      • declaration_date214-09-2023
      • placebo_presentYes
      • study_objectives<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Objective</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n To evaluate the change in weight (standardized for age) of infants receiving Bi-26</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Key Secondary Objective</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n To evaluate the change in weight of infants receiving Bi-26</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Secondary Objectives</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n ​​To estimate the treatment response over time associated with Bi-26</li>\n <li style=\"line-height: 20px;\">\n To assess the proportion of infants who achieve a specified change in WAZ from baseline to Day 56</li>\n <li style=\"line-height: 20px;\">\n To assess the proportion of infants who achieve a specified WAZ at Day 56</li>\n <li style=\"line-height: 20px;\">\n To assess the re-hospitalization rate</li>\n <li style=\"line-height: 20px;\">\n To assess the safety of Bi-26 supplementation through End of Study (EoS, Day 90 visit)</li>\n <li style=\"line-height: 20px;\">\n To measure engraftment of B. infantis in participants</li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Exploratory Objectives</strong></div>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To describe stool biomarkers in response to Bi-26 supplementation in terms of stool composition (e.g., microbiome, pH)</li>\n <li style=\"line-height: 20px;\">\n To describe the blood biomarkers (e.g., inflammation, metabolomics), in response to Bi-26 supplementation</li>\n</ul>\n
      • principal_inclusion_criteria<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Age</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Participant must be between 30 days and 120 days of age (inclusive), at the time of enrollment (study Day 1)</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Type of Participant and Disease Characteristics</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Hospitalized for acute non-surgical illness</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. Completed acute stabilization phase of treatment, including fluid rehydration and antibiotic course, prior to enrollment (study Day 1)</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Weight</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4. WAZ at enrollment (study Day 1) is less than negative 2 (<-2)</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Sex</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 5. Any</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Informed consent</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 6. Participant’s parent(s)/legal guardian is capable of giving informed consent which includes agreement to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <div>\n <strong>Additional requirements</strong></div>\n <div>\n 7. Participant’s parent(s)/legal guardian agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study</div>\n <div>\n 8. Participant’s parent(s)/legal guardian has easy access to reliable refrigeration (for storage of investigational product)</div>\n <div>\n 9. Participant receives some feedings from breastmilk and mother intends to continue breastfeeding.</div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Congenital condition (suspected or confirmed) that the investigator considers likely to interfere with feeding or with normal growth and development</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Infant has not been discharged from hospital since birth or has not been at home for at least one week since birth</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. Infant hospitalized with septic shock during current hospitalization</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4. Infant required mechanical ventilation during current hospitalization</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 5. Infant with acute kidney injury on hospital admission</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 6. Infant with severe jaundice and suspected kernicterus</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 7. Infant receiving treatment for suspected or confirmed tuberculosis, or suspected or confirmed HIV infection</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 8. Ongoing infant antibiotic (e.g. as prophylaxis in sickle cell disease) and/or probiotic usage</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 9. Ongoing maternal antibiotic and/or probiotic usage for breast-feeding infants</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 10. Inability of participant’s parent(s)/legal guardian to comply with protocol requirements, as per investigator assessment.</div>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Endpoints</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n WAZ change from baseline (Day 1) to the Day 56 visit in Bi-26 group</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Key Secondary Endpoints</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Change in weight (in grams) from baseline (Day 1) to the Day 56 visit in the Bi-26 group</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Secondary Endpoints</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n WAZ change from baseline (Day 1) over time through the Day 90 visit (longitudinal assessment) by duration of dosing</li>\n <li style=\"line-height: 20px;\">\n Proportion of infants with a ≥ 0.3, ≥ 0.4, and ≥ 0.5 change in WAZ from baseline (Day 1) to Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Proportion of infants who achieve a WAZ > -2 at Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Number of re-hospitalizations for acute non-surgical illness through the Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Number of adverse events (AEs) and serious adverse events (SAEs) through Day 90</li>\n <li style=\"line-height: 20px;\">\n Presence of B. infantis in stool on Days 1, 28, 56, and 90</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Exploratory Endpoints</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Stool biomarkers on Days 1, 28, and 56</li>\n <li style=\"line-height: 20px;\">\n Blood biomarkers on Days 1 and 28</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • 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 The study will be conducted in Homa Bay County, western Kenya. The main site will be Homa Bay County Teaching and Referral Hospital, with the surrounding sub-county hospitals (Marindi, Makongeni, Rangwe Ndhiwa and Mbita), health centres (Nyalkinyi), dispensaries (Otaro, Ogande, Wiga, Koduogo, Nyamasi, Pedo, Imbo, Kijawa, Miniambo, Pala Masogo and Orego) and private health facilities (St. Paul, Samarimed and St. Lawrence) referring cases to the main hospital. </p>\n<p>\n  </p>\n<p>\n <strong>Simon Kariuki, PhD,</strong> is Chief Research Officer and the Malaria Branch Chief at KEMRI, CDC and LSTM Collaborative Program in Kisumu, Kenya. He is the PI of this study and will facilitate project procedures in Kenya and act as the main liaison between the investigators and KEMRI and the local regulator and other relevant authorities.  He will also be responsible for the overseeing the development of the site-specific protocol, standard operating procedures (SOPs), training of personnel, recruitment of study participants. He will provide all the onsite oversight during study conduct, data collection, interpretation and manuscript preparation.</p>\n<p>\n  </p>\n<p>\n <strong>Prof. Stephen Allen, (MB, ChB; DTM&H; MD; FRCPCH) </strong>is a paediatric gastroenterologist undertaking clinical practice in the Gambia.  As a co-investigator, he will provide technical advice on various aspects of the study in collaboration with other co-investigators involved<strong>.</strong></p>\n<p>\n  </p>\n<p>\n <strong>Iwaret Otiti, MBChB, MSc</strong>, is a medical doctor with training in epidemiology. She will participate in managing the clinical trial in close consultation with the Principal Investigator and other Co-Investigators. She will be responsible for amendments to the study protocol, obtaining ethics and regulatory clearances and standard operating procedures, and coordinating the fieldwork in Kenya. She will also be responsible for overseeing any centralised functions including the coordination of data management and laboratory testing and oversee provision of clinical care to study participants and supervision of clinical officers and other study staff. She will also participate in reporting of SAEs, data collection and preparation of manuscripts.</p>\n<p>\n  </p>\n<p>\n <strong>Kephas Otieno, MSc</strong>, is the head of the Malaria laboratory of the KEMRI, CDC and LSTM Collaborative Program in Kisumu, Kenya. He will be responsible for training and supervision of staff involved in collection of laboratory samples. He will also provide oversight over the processing, storage/archiving and shipment of all samples. He will coordinate the quality assurance/quality control aspects of the study.</p>\n<p>\n  </p>\n<p>\n <strong>Ruth Njoroge, BPharm,</strong> is the KEMRI/CGHR pharmacist. She will participate in the implementation of the study, oversee handling of investigational product, training of staff on data collection on pharmacovigilance and reporting to the Kenya Pharmacy and Poisons Board (KPPB). She will also participate in the interpretation of data and the preparation of manuscripts.</p>\n<p>\n  </p>\n<p>\n <strong>Micah June, BSc,</strong> will participate in planning the study, recruitment, training and supervision of clinic and field staff, data collection, reporting of SAEs, quality control and assurance including oversee other regulatory roles, and manuscript preparation.</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">This study focuses on infants in low- and middle-income countries as these are the regions where the burden of disease is greatest as noted in the protocol and the IB. Approximately 90% of underweight children are found in Southeast Asia and Sub-Saharan Africa (</span><a aria-label=\"Link Food Sci Nutr.\" class=\"fui-Link ___1qmgydl f3rmtva f1ewtqcl fyind8e f1k6fduh f1w7gpdv fk6fouc fjoy568 figsok6 f1hu3pq6 f11qmguv f19f4twv f1tyq0we f1g0x7ka fhxju0i f1qch9an f1cnd47f fqv5qza f1vmzxwi f1o700av f13mvf36 f1cmlufx f9n3di6 f1ids18y f1tx3yz7 f1deo86v f1eh06m1 f1iescvh ftqa4ok f2hkw1w fhgqx19 f1olyrje f1p93eir f1h8hb77 f1x7u7e9 f10aw75t fsle3fq\" font-size:=\"\" href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007294/\" overflow-wrap:=\"\" rel=\"noreferrer noopener\" style=\"color: rgb(51, 51, 51); text-decoration-line: none; font-family: \" target=\"_blank\" title=\"https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9007294/\" trebuchet=\"\">Food Sci Nutr.</a><span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\"> 2022 Apr; 10(4): 1167–1174. </span><a aria-label=\"Link Published online 2022 Jan 18. doi: 10.1002/fsn3.2748\" class=\"fui-Link ___1qmgydl f3rmtva f1ewtqcl fyind8e f1k6fduh f1w7gpdv fk6fouc fjoy568 figsok6 f1hu3pq6 f11qmguv f19f4twv f1tyq0we f1g0x7ka fhxju0i f1qch9an f1cnd47f fqv5qza f1vmzxwi f1o700av f13mvf36 f1cmlufx f9n3di6 f1ids18y f1tx3yz7 f1deo86v f1eh06m1 f1iescvh ftqa4ok f2hkw1w fhgqx19 f1olyrje f1p93eir f1h8hb77 f1x7u7e9 f10aw75t fsle3fq\" font-size:=\"\" href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007294/\" overflow-wrap:=\"\" rel=\"noreferrer noopener\" style=\"color: rgb(51, 51, 51); text-decoration-line: none; font-family: \" target=\"_blank\" title=\"https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9007294/\" trebuchet=\"\">Published online 2022 Jan 18. doi: 10.1002/fsn3.2748</a><span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">). Thus, countries in these regions were selected for participation in this study, including Kenya, as there is an unmet medical need for management of underweight infants in those regions.</span></p>\n
      • other_details_regulatory_notapproved<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Pakistan - 28 Dec 2022</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Tanzania - 30 Dec 2022</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Bangladesh - planned for mid-July 2023</p>\n
      • other_details_regulatory_approved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">All approvals are pending</span></p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable</span></p>\n
      • other_details_regulatory_halted<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable</span></p>\n
      • estimated_durationThe study duration for each participant is approximately 3 months.
      • 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_comparatorpotato maltodextrin
      • 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_sites8
      • multi_country_listKenya, Tanzania, Pakistan and Bangladesh
      • data_monitoring_committeeYes
      • total_enrolment_per_siteMinimum per site = 5, maximum per site = 30
      • total_participants_worldwide396
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyMalnourished infants
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Lucas
      • investigator1_middle_nameOtieno
      • investigator1_family_nameTina
      • investigator1_qualificationMBChB, MPH DLSHTM
      • investigator1_professional_addressVictoria Biomedical Research Institute, Kisumu County Referral Hospital Off Ang\'awa Road, P.O. Box 7180, Postal Code 40100, Kisumu, Kenya
      • investigator1_telephone+254708358451
      • investigator1_emailltina@vibriafrica.org
      • organisations_transferred_Yes
      • number_participants160
      • notification<p>\n The study has already been reviewed and approved by KPPB on 31 July 2023. This included the site of Dr Lucas Tina. This application is the submission of an additional site of Dr Simon Kariuki.</p>\n
      • approval_date19-12-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-09-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonAll reviewer comments have been addressed.
      • final_report
      • implication_results
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2025-04-24 16:21:11
      • created2023-09-05 14:26:18
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id961
        • application_id1312
        • given_nameDr Simon
        • middle_name
        • family_nameKariuki
        • qualificationBsc. Mphil, PhD, Post-Doc
        • professional_address.or 8088, Eldoret, Kenya
        • telephoneTel: +254 (0) 57 2022902, 2022929,
        • emailskkariuki@kemri.org
        • created2023-09-05 14:32:11
        • modified2023-09-14 16:38:40
    • SiteDetail(array)
      • 0(array)
        • id1587
        • application_id1312
        • county_id42
        • site_nameKenya Medical Research Institute- Centre for Global Health Research
        • physical_addressKisian Campus, Off Kisumu-Busia Highway, P.O.Box 1578-40100, Kisumu, Kenya
        • contact_details+254 725 389 246
        • contact_personDr Simon Kariuki
        • site_capacity(null)
        • misc(null)
        • created2023-09-05 14:32:11
        • modified2023-09-14 16:38:40
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id689
        • application_id1312
        • sponsorBill & Melinda Gates Medical Research Institute
        • sponsor_typeResearch Institution
        • contact_personJanie Parrino
        • addressOne Kendall Square Building 600,Cambridge, Massachusetts, 02139, United States
        • telephone_number+12155397606
        • fax_number
        • cell_numberN/A
        • email_addressjanie.parrino@gatesmri.org
        • created2023-09-05 14:32:11
        • modified2023-09-14 16:38:40
  • 2(array)
    • Application(array)
      • id1303
      • user_id693
      • trial_status_id1
      • abstract_of_study<p>\n STUDY RATIONALE The purpose of this study is to assess the efficacy and safety of astegolimab compared with placebo in participants with chronic obstructive pulmonary disease (COPD) who are former or current smokers and have a history of frequent exacerbations. OBJECTIVES AND ENDPOINTS Primary and selected secondary objectives for the study are expressed using the estimand framework in accordance with the International Conference on harmonization E9 (R1) statistical principles for clinical trials (FDA 2020) in Section 3. The objectives include (but are not limited to) the evaluation of the efficacy and safety of astegolimab compared with placebo. OVERALL DESIGN This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of astegolimab in combination with standard of care (SOC) compared with placebo in combination with SOC, in participants with COPD who are former or current smokers and have a history of frequent exacerbations. Approximately 1290 participants with COPD are expected to be enrolled globally. Following a screening period of at least 7 days and to up to 4 weeks, participants will be randomized in a 1:1:1 ratio to 1 of 3 treatment arms to receive blinded treatment with either astegolimab or placebo. Randomization will be stratified by smoking status at screening (former smoker vs. current smoker) and region. The first dose of study drug (astegolimab or placebo) will be administered on Day 1; treatment will continue through Week 50, followed by a 12-week safety follow-up period. The treatment regimens for each arm are as follows: Astegolimab 476 mg SC every 2 weeks (Q2W) Astegolimab 476 mg SC every 4 weeks (Q4W) To ensure that all study participants undergo the same visit schedule, participants randomized to the Q4W dosing arm will alternate between injections of astegolimab and placebo Q2W (beginning with astegolimab on Day 1), thus receiving astegolimab Q4W. Placebo SC Q2W Participants will return to the clinic Q2W through the treatment completion visit at Week 52. The primary endpoint analyses will be conducted using the 52-week treatment period data for all participants. Several key aspects of the study design and study population are summarized below. Phase: Phase 3 Population Type: Adult patients of any gender Control Method: Placebo Population Diagnosis or Condition: Chronic obstructive pulmonary disease Interventional Model: Parallel group Population Age: 40-80 years Test Compound{s}: Astegolimab Site Distribution: Multi-site and multi-region Active Comparator: Not applicable Study Intervention Assignment Method: Randomization and stratification Number of Arms: 3 Number of Participants to Be Enrolled: Approximately 1290 participants STUDY TREATMENT Astegolimab and placebo will be supplied by the Sponsor as a sterile liquid in 2.25 mL pre-filled syringes with a needle safety device, providing 238 mg/1.7 mL of astegolimab or placebo. Study drug administration must occur after all other procedures have been completed at the visit, unless specifically indicated otherwise. Study drug will be administered by trained medical personnel. Each dose of study drug (astegolimab or placebo) will be administered as 2 SC injections (for a total of 3.4 mL), with each injection administered on a different side of the abdomen (i.e., right or left). All participants will be observed for at least 30 minutes after each dose and longer (approximately 60 minutes) in the event of an injection-site reaction, as determined by the investigator. If a participant develops any signs or symptoms to suggest a systemic hypersensitivity reaction or anaphylactic event, longer observation may be warranted as per the opinion of the investigator. There must be a minimum of 8 days between doses. In the event a dosing visit would occur within 8 days of a subsequent or previous dosing visit (e.g., due to an out-of-window visit), the study drug may not be administered. Instead, the next dose of study drug should be administered at the subsequent scheduled visit within the protocol-defined visit window to ensure that the 8-day minimum dosing interval is maintained. DURATION OF PARTICIPATION The total duration of study participation for each individual is expected to be approximately 15 months.</p>\n
      • study_title<p>\n A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE</p>\n
      • laymans_summary<p>\n Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by irreversible changes in air flow causing progressive obstruction. The prevalence of diagnosed COPD has dramatically increased over recent years and is among the leading causes of disabilities and mortality. The airflow obstruction among COPD patients is largely linked with long-term morbidity and comorbidities such as hypertension, diabetes, ischemic heart disease, stroke, and heart failures were reported in patients with exacerbated COPD cases. These comorbidities are often linked with smoking, systemic inflammation, airflow limitation, and aging. These comorbidities do not only negatively impact the patients’ quality of life but also lower their survival rate. Although cigarette smoking is traditionally known as the predominant cause of COPD, there have been increasing cases of non-smokers being diagnosed with the disease. COPD is more prevalent among the older population, with the rising prevalence and mortality among women than male, attributed from increased population of female smokers. Other risk factors include occupational exposure to chemical fumes, air pollution, childhood infection, and genetic heredity. Spirometry is regarded as the gold standard diagnostic tool for COPD which can detect COPD at early, asymptomatic stages. There is no cure for COPD, however, there are availability of therapies that can improve symptoms and a patients’ quality of life. Despite the treatment advances, there is still an unmet need for improved pharmacological intervention against COPD, particularly in the reduction of exacerbations and modifying the disease progression. Astegolimab is a drug that is under development for the treatment of patients with COPD. This study will focus on finding out if astegolimab is safe and if it works in comparison to placebo as a treatment for COPD patients who are current or former smokers with a history of frequent exacerbations. If found to be efficacious, participants will be given access to the study drug in an Open Label Extension study (GB43374) subject to approval by relevant health authorities. </p>\n
      • short_titleARNASA
      • protocol_noECCT/23/09/01
      • version_no4
      • date_of_protocol20-06-2023
      • study_drugAstegolimab (RO7187807)
      • disease_conditionChronic obstructive pulmonary disease (COPD)
      • 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_nameAstegolimab (RO7187807)
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressPPDSubmissionsMembers.SM@ppd.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_applicantPhoebe.Otieno@ppd.com
      • declaration_date101-09-2023
      • declaration_principal_investigatorProf Videlis Nduba
      • declaration_date201-09-2023
      • placebo_presentYes
      • study_objectives<p>\n <strong>The study objectives are listed below:</strong></p>\n<p>\n To evaluate the efficacy of astegolimab compared with placebo</p>\n<p>\n To evaluate the safety of astegolimab compared with placebo </p>\n<p>\n To characterize the astegolimab PK profile</p>\n<p>\n To evaluate the immune response to astegolimab</p>\n<p>\n To evaluate potential relationships between selected covariates and exposure to astegolimab</p>\n<p>\n To evaluate the efficacy of astegolimab compared with placebo</p>\n<p>\n To evaluate the safety of astegolimab compared with placebo</p>\n<p>\n To evaluate potential relationships between drug exposure and the efficacy and safety of astegolimab</p>\n<p>\n To evaluate potential effects of ADAs</p>\n<p>\n To identify and/or evaluate biomarkers that are predictive of response to astegolimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), can provide evidence of astegolimab activity (i.e., PD iomarkers), or can increase the knowledge and understanding of disease biology and drug safety or pharmacokinetics</p>\n<p>\n To evaluate health status utility scores of participants treated with astegolimab compared with placebo</p>\n
      • principal_inclusion_criteria<p>\n 1. Able and willing to provide written informed consent and to comply with the study protocol</p>\n<p>\n 2. Age 40-80 years at Visit 1</p>\n<p>\n 3. Documented COPD diagnosis for > 12 months prior to Visit 1</p>\n<p>\n 4. History of frequent exacerbations, defined as having had 2 or more moderate or severe COPD exacerbations within 12 months prior to Visit 1 A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnoea, sputum volume, and sputum purulence) that lead to treatment with systemic corticosteroids (oral, IV, or intramuscular [IM]) and/or antibiotics. Prior use of antibiotics alone does not qualify as a moderate exacerbation unless the use was specifically for the treatment of worsening symptoms of COPD. A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration 24 hours) or lead to death.</p>\n<p>\n 5. Post-bronchodilator FEV1 >20% and <80% of predicted at Visit 1 or Visit 2</p>\n<p>\n 6. Post-bronchodilator FEV1/FVC < 0.70 at Visit 1 or Visit 2</p>\n<p>\n 7. mMRC score >2 at screening</p>\n<p>\n 8. Current tobacco smoker or former smoker (having stopped smoking for at least 6 months prior to Visit 1) with a history of smoking > 10 pack-years (e.g., 20 cigarettes/day for 10 years) At Visit 1, participants who meet the protocol definition of current smoker will receive smoking cessation counselling</p>\n<p>\n 9. On optimized COPD maintenance therapy as defined below for > 12 months prior to Visit 1. – Inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA) – Long-acting muscarinic antagonist (LAMA) plus LABA – ICS plus LAMA plus LABA Participants must be stable on current medications and doses for at least 4 weeks prior to Visit 1. Initiation of new COPD therapy, including a methylxanthine preparation, maintenance macrolide therapy, and/or phosphodiesterase 4 (PDE4) inhibitor is not permitted within 4 weeks prior to Visit 1.</p>\n<p>\n 10. Chest X-ray or computed tomography (CT) scan within 6 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 2) that confirms the absence of clinically significant lung disease besides COPD</p>\n<p>\n 11. Demonstrated ability to use and comply with electronic diary (eDiary) requirements, defined as completion of all questions on at least 5 of 7 days prior to Visit 2 Participants unable to demonstrate compliance with the eDiary during the screening period will be screen failed. Participants will have the opportunity to demonstrate eDiary compliance if rescreened (see Protocol Version 2 dated 09 Nov 2022 Section 8.3.3.3). 12. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Female participants must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for</p>\n<p>\n 12 weeks after the final dose of astegolimab. A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state ( 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a female participant with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. Examples of contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.</p>\n<p>\n 13. For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partner, male participants must remain abstinent or use a condom during the treatment period and for 12 weeks after the final dose of astegolimab to avoid exposing the embryo. Male participants must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form</p>\n
      • principal_exclusion_criteria<div>\n <p style=\"margin-left:22.0pt;\">\n <strong>2                EXCLUSION CRITERIA</strong></p>\n <p>\n  </p>\n <ul>\n <li style=\"margin-left: 22pt;\">\n Potential participants are excluded from the study if any of the following criteria apply:</li>\n <li style=\"margin-left: 22pt;\">\n History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the study drug</li>\n <li style=\"margin-left: 22pt;\">\n  Any prior treatment with astegolimab</li>\n </ul>\n</div>\n<div>\n <ul>\n <li style=\"margin-left: 22pt;\">\n Current documented diagnosis of asthma</li>\n <li style=\"margin-left: 22pt;\">\n History of clinically significant pulmonary disease other than COPD</li>\n <li style=\"margin-left: 22pt;\">\n Diagnosis of a-1-antitrypsin deficiency</li>\n <li style=\"margin-left: 22pt;\">\n History of long-term treatment with oxygen at > 4.0 liters/minute While breathing supplemental oxygen, the participant should demonstrate an oxyhemoglobin saturation of ³ 89%.</li>\n <li style=\"margin-left: 22pt;\">\n Lung volume reduction surgery or procedure within 12 months prior to Visit 1</li>\n <li style=\"margin-left: 22pt;\">\n Individuals participating in, or scheduled for, an intensive COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible)</li>\n <li style=\"margin-left: 22pt;\">\n History of lung transplant</li>\n <li style=\"margin-left: 22pt;\">\n Any infection that resulted in hospital admission for ³ 24 hours and/or treatment with oral, IV, or IM antibiotics within 4 weeks prior to Visit 1 or during screening Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening</li>\n <li style=\"margin-left: 22pt;\">\n Treatment with oral, IV, or IM corticosteroids (> 10 mg/day prednisolone or equivalent) within 4 weeks prior to initiation of study drug</li>\n <li style=\"margin-left: 22pt;\">\n Treatment with investigational therapy within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening</li>\n <li style=\"margin-left: 22pt;\">\n Treatment with a licensed biologic agent (e.g., omalizumab, dupilumab, and/or anti-IL-5 therapies) within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening</li>\n <li style=\"margin-left: 22pt;\">\n Initiation of or change in non-biologic immunomodulatory or immunosuppressive therapy within 3 months prior to screening</li>\n <li style=\"margin-left: 22pt;\">\n Treatment that is considered palliative (e.g., for life expectancy < 12 months)</li>\n <li style=\"margin-left: 22pt;\">\n Planned surgical intervention during the study</li>\n <li style=\"margin-left: 22pt;\">\n Receipt of a live attenuated vaccine within 4 weeks prior to Visit 1 or during screening</li>\n <li style=\"margin-left: 22pt;\">\n Known immunodeficiency, including but not limited to, HIV infection</li>\n <li style=\"margin-left: 22pt;\">\n Where required by local regulations: Patients must have a negative HIV test result at screening or within 3 months prior to screening.</li>\n <li style=\"margin-left: 22pt;\">\n Known evidence of active or untreated latent tuberculosis</li>\n <li style=\"margin-left: 22pt;\">\n Where required by local regulations: Patients must have a negative tuberculosis test result at screening or within 3 months prior to screening.</li>\n <li style=\"margin-left: 22pt;\">\n AST, ALT, or total bilirubin elevation ³ 2.0 ´ the upper limit of normal (ULN ) during screening</li>\n <li style=\"margin-left: 22pt;\">\n Substance abuse, as determined by the investigator, within 12 months prior to screening</li>\n <li style=\"margin-left: 22pt;\">\n History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, or ductal carcinoma in situ</li>\n <li style=\"margin-left: 22pt;\">\n Any other serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant’s safe participation in and completion of the study</li>\n <li style=\"margin-left: 22pt;\">\n Unstable cardiac disease, myocardial infarction, or New York Heart Association</li>\n <li style=\"margin-left: 22pt;\">\n Class III or IV heart failure within 12 months prior to screening</li>\n <li style=\"margin-left: 22pt;\">\n History or presence of an abnormal ECG that is deemed clinically significant by the investigator, including complete left bundle branch block or second- or third-degree atrioventricular heart block</li>\n <li style=\"margin-left: 22pt;\">\n QT interval corrected through use of Fridericia’s formula (QTcF) > 450 ms if the participant is male or QTcF > 470 ms if the participant is female</li>\n <li style=\"margin-left: 22pt;\">\n For male or female participants with QRS > 120: QTcF > 480 ms.</li>\n <li style=\"margin-left: 22pt;\">\n History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, significant left ventricular hypertrophy with strain), or family history of sudden unexplained death or long QT syndrome</li>\n <li style=\"margin-left: 22pt;\">\n Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of astegolimab</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n  </p>\n<p style=\"margin-left:25.6pt;\">\n <strong><u>O</u></strong><strong><u>BJECTIVES AND ENDPOINTS</u></strong></p>\n<p style=\"margin-left:25.6pt;\">\n Primary and selected secondary objectives for the study are expressed using the estimand framework in accordance with the International Conference on Harmonization E9 (R1) statistical principles for clinical trials (FDA 2020) in Section 3.</p>\n<p>\n  </p>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:228px;height:19px;\">\n <p style=\"margin-left:42.55pt;\">\n <strong>Pr</strong><strong>imary Objective</strong></p>\n </td>\n <td style=\"width:348px;height:19px;\">\n <p style=\"margin-left:83.25pt;\">\n <strong>E</strong><strong>stimand Definition</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:15px;\">\n <p style=\"margin-left:3.3pt;\">\n ·  To evaluate the efficacy of</p>\n </td>\n <td style=\"width:348px;height:15px;\">\n <p style=\"margin-left:3.3pt;\">\n ·  Population: participants with COPD who are former or</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:15px;\">\n <p style=\"margin-left:13.05pt;\">\n astegolimab compared with</p>\n </td>\n <td style=\"width:348px;height:15px;\">\n <p style=\"margin-left:13.15pt;\">\n current smokers and have a history of frequent</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:46px;\">\n <p style=\"margin-left:13.05pt;\">\n placebo</p>\n </td>\n <td style=\"width:348px;height:46px;\">\n <p style=\"margin-left:13.15pt;\">\n exacerbations, as defined by the inclusion and</p>\n <p style=\"margin-left:13.15pt;\">\n exclusion criteria, and received at least one dose of study drug</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:48px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:348px;height:48px;\">\n <p style=\"margin-left:24.9pt;\">\n ·       Endpoint: annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:169px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:348px;height:169px;\">\n <p style=\"margin-left:40.15pt;\">\n <strong>–   </strong>A moderate COPD exacerbation is defined as new or increased COPD symptoms</p>\n <p style=\"margin-left:40.15pt;\">\n (e.g., dyspnea, sputum volume, and sputum</p>\n <p style=\"margin-left:40.15pt;\">\n purulence) that lead to treatment (duration</p>\n <p style=\"margin-left:40.15pt;\">\n ³ 3 days) with systemic corticosteroids (oral, IV,</p>\n <p style=\"margin-left:40.15pt;\">\n or IM) at a dose of > 10 mg/day prednisolone</p>\n <p style=\"margin-left:40.15pt;\">\n equivalent and/or antibiotics</p>\n <p style=\"margin-left:40.15pt;\">\n <strong>–   </strong>A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration > 24 hours) or lead</p>\n <p style=\"margin-left:40.15pt;\">\n to death</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:19px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:348px;height:19px;\">\n <p style=\"margin-left:3.3pt;\">\n ·  Treatment:</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:52px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:348px;height:52px;\">\n <p style=\"margin-left:46.55pt;\">\n <strong>–      </strong>Experimental: astegolimab 476 mg SC Q2W Experimental: astegolimab 476 mg SC Q4W</p>\n <p style=\"margin-left:24.9pt;\">\n <strong>–      </strong>Control: placebo SC Q2W</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:19px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:348px;height:19px;\">\n <p style=\"margin-left:3.3pt;\">\n ·  Intercurrent events and handling strategies:</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:33px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:348px;height:33px;\">\n <p style=\"margin-left:24.9pt;\">\n <strong>–      </strong>Early discontinuation from study treatment:</p>\n <p style=\"margin-left:46.55pt;\">\n treatment policy strategy</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:228px;height:36px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:348px;height:36px;\">\n <p style=\"margin-left:13.15pt;\">\n ·  Population-level summary: RR for annualized rate of moderate and severe COPD exacerbations</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • 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_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The study site is the University of Nairobi Clinical Research Centre (UNCRC) located in the Department of Human Anatomy and Medical Physiology at the Chiromo Campus of the University of Nairobi Faculty of Health Sciences. In this location administrative and archiving facilities are domiciled. The clinic facilities will be physical located in the KNH RIDU and laboratory facilities will be at the KAVI ICR. Recruitment, consenting, randomization and administration of IMP will be at the RIDU unit the chest clinic number 17. The research medical records unit, administrative offices, storage of the IP, laboratory testing and specimen packaging for shipping will be done at the KAVI ICR . which is well-staffed by trained personnel with expertise in the following research related tasks: Clinical officers: Participate in screening of potential patients based on the inclusion and exclusion criteria. Clinical Research Nurses: Obtain Informed consents, Make CRF entries/resolve queries; Collect medical information; Vital signs; Collect adverse events; Administer IP; Collect lab samples; Participant recruitment and retention. Pharmacist and Pharmacy Technologist: Investigational Drug Services: Manage IP receipt/return; Prepare and dispense IP; Unbinding procedures. Regulatory Affairs: Manage submissions to ethics and regulatory authorities. Maintain essential documents and ensure compliance Contracts and Budgets: Maintain legal and financial documents; Ensure appropriate invoicing to the sponsor; Ensure appropriate processes for research covered procedures versus patients’ standard of care Data Management: Make CRF entries/resolve queries; Maintain the patients’ research documents Clinical Research operations: Oversight of UNCRC studies and staff; support all research staff with their tasks Investigators: Obtain Informed Consent; Assess eligibility; Make CRF entries/resolve Queries; Medical decisions/review; Collect medical information; Vital signs; Assess 8 Ordinal Scale; Collect/Assess Adverse Events; Administer IP; Conduct Physical Exam; Collect Lab Samples; Maintain Essential Documents; IP processes The KNH Chest Clinic is part of the Respiratory Infectious Disease Unit (RIDU). The facility is designed to provide an integrated, patient-centered service across the care cycle from diagnosis, treatment, surveillance and palliative care. The ambulatory chest clinic also offers streamlined, efficient care by a multidisciplinary team of respiratory specialists. This coordinated approach provides comprehensive care and support for patients with lung disease and their caregivers. All patients treated at the KNH Respiratory Infectious Disease Unit (RIDU) will have access to smoking cessation, psychosocial and support counseling as well as palliative care support as part of best practice. This is not limited to non-study patients and thus is available to study patients as well. The UNCRC provides an approach to care which is guided by international standards including accreditation by the Kenya Medical Laboratory Technician and Technologist Board (KMLLTB) and IATA Shipping and Transport of Regulated Biologic Material certification. </p>\n
      • other_details_explanation<p>\n Switzerland is the host country and Sponsor intends to submit study for approval in the host country. </p>\n
      • other_details_regulatory_notapproved<div>\n  </div>\n<div>\n <table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 74px;\">\n <p style=\"margin: 0px 0px 10px;\">\n # Sites</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 378px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submission to RA</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 208px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Mexico</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 74px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 8</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 378px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submission completed for 2 sites on 16-Dec à approval expected in May</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 208px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Guatemala</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 74px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 5</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 378px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Only EC submission completed; first MoH submission planned end of Feb.</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 208px;\">\n <p style=\"margin: 0px 0px 10px;\">\n South Africa</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 74px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 11</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 378px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submission completed for all sites on 24-Feb à approval expected in May</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 208px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Kenya</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 74px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 9</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 378px;\">\n <p style=\"margin: 0px 0px 10px;\">\n No Approvals yet</p>\n </td>\n </tr>\n </tbody>\n </table>\n <p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n</div>\n<p>\n  </p>\n
      • other_details_regulatory_approved<div>\n  </div>\n<div>\n <table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 74px;\">\n <p style=\"margin: 0px 0px 10px;\">\n # Sites</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 378px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submission to RA</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 208px;\">\n <p style=\"margin: 0px 0px 10px;\">\n United States</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 74px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 36</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 378px;\">\n <p style=\"margin: 0px 0px 10px;\">\n the current protocol amendment V5.0_11-Oct-2022 has been approved on 07-Dec-2022</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 208px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Dominican Rep</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 74px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 6</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 378px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submission completed for 4 sites between 31-Jan and 7-Feb à 1 final approval received</p>\n </td>\n </tr>\n </tbody>\n </table>\n <p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n</div>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_durationThe total duration of study participation for each individual is expected to be approximately 15 months.
      • 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_states39
      • number_of_sitesApproximately 6 sites will participate in Kenya. As approvals from the Local Ethics Committees (LECs) are obtained to avoid delays in site-activation as each site submits to their LEC at different timepoints.
      • multi_country_listChin ; Hong Kong; India; Korea, Republic of; New Zealand; Philippines; Taiwan, Province of China; Thailand; Vietnam;\nArgentina; Brazil; Chile; Mexico; Canada; United States; Egypt; Israel; Kenya; South Africa; Switzerland; Turkey; United\nKingdom; Austria; Belgium; Bulgaria; Czech Republic; Denmark; France; Germany; Greece; Hungary; Italy; Latvia; Netherlands;\nPoland; Romania; Spain; Sweden; Australia
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNo maximum nor minimum enrolment per site as enrolment is competitive worldwide, but it is expected that approximately 2\n- 3 participants will participate per site.\n
      • total_participants_worldwideApproximately 1290 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_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • 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_nameProfessor Videlis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressKenyatta National Hospital Grounds, Off Hospital Road, Behind Government Chemist, P.O. BOX 47855-00100, Nairobi, Kenya
      • investigator1_telephone+254790484654
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participantsEnrolment is competitive worldwide. Approximately 12 participants will participate in Kenya.\n
      • notification<p>\n None</p>\n
      • approval_date24-11-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-01-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonAll reviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-05-07 15:38:45
      • created2023-08-30 16:16:18
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id960
        • application_id1303
        • given_nameDr Mary
        • middle_name
        • family_nameMatilu
        • qualificationMedical Doctor
        • professional_addressKEMRI-Mtwapa Clinical Research Annex _P.O. Box 428-80108, Mtwapa, Kenya
        • telephone+254 722 523370
        • emailinzianimatilu@gmail.com
        • created2023-08-30 17:02:23
        • modified2024-01-03 14:20:06
    • SiteDetail(array)
      • 0(array)
        • id1580
        • application_id1303
        • county_id3
        • site_nameKEMRI-Mtwapa Clinical Research Annex,
        • physical_address- KEMRI-Mtwapa Clinical Research Annex,
        • contact_detailsP.O. Box 428-80108, Mtwapa- Kilifi County, Kenya
        • contact_personDr Mary Matilu
        • site_capacity(null)
        • misc(null)
        • created2023-08-30 17:02:23
        • modified2024-01-03 14:20:06
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 1(array)
        • id1581
        • application_id1303
        • county_id47
        • site_nameUniversity of Nairobi Clinical Research Centre
        • physical_addressProf Mungai Road Off Wasawo Drive Off Riverside Drive Chiromo Campus University Of Nairobi P.O. Box 19676 00202 Nairobi Kenya
        • contact_details+254 707028067
        • contact_personDr Teresa Kinyari
        • site_capacity(null)
        • misc(null)
        • created2023-08-31 12:35:16
        • modified2024-01-03 14:20:06
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1582
        • application_id1303
        • county_id47
        • site_nameCenter for Research In Tropical Medicine and Community Development
        • physical_addressP.O. Box 6387, Thika, Kenya
        • contact_details+254722425613
        • contact_personDr Jesse Gitaka
        • site_capacity(null)
        • misc(null)
        • created2023-08-31 12:37:34
        • modified2024-01-03 14:20:06
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id1583
        • application_id1303
        • county_id16
        • site_nameClinical Research Health Network (CREA-N)
        • physical_addressMachakos Level 5 Hospital Site P.O. Box 19 -90100 Machakos Kenya
        • contact_details+254115021107
        • contact_personDr Jacqueline Mirera
        • site_capacity(null)
        • misc(null)
        • created2023-08-31 12:40:06
        • modified2024-01-03 14:20:06
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
      • 4(array)
        • id1584
        • application_id1303
        • county_id41
        • site_nameKEMRI-CRDR Siaya Clinical Research Annex
        • physical_addressSiaya County Referral Hospital Grounds, P.O. BOX 40600-144, Siaya, Kenya
        • contact_details+254700111395 / +254731141831
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-08-31 12:40:06
        • modified2024-01-03 14:20:06
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 5(array)
        • id1585
        • application_id1303
        • county_id47
        • site_nameKEMRI-CRDR Clinical Research Annex
        • physical_addressKenyatta National Hospital Grounds, Off Hospital Road, Behind Government Chemist, P.O. BOX 47855-00100, Nairobi, Kenya
        • contact_details+254790484654
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-08-31 12:44:42
        • modified2024-01-03 14:20:06
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 6(array)
        • id1586
        • application_id1303
        • county_id16
        • site_nameClinical Research Health Network (CREA-N)
        • physical_addressMachakos Level 5 Hospital Site P.O. Box 19 -90100 Machakos Kenya
        • contact_details+254115021107
        • contact_personDr Jacqueline Mirera
        • site_capacity(null)
        • misc(null)
        • created2023-08-31 12:45:25
        • modified2024-01-03 14:20:06
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
    • Sponsor(array)
      • 0(array)
        • id688
        • application_id1303
        • sponsorF. Hoffmann-La Roche Ltd
        • sponsor_typeIndustry
        • contact_personNadia Walli
        • addressClinical Research (PDG - CCO, North America),7070 Mississauga Road Mississauga, ON L5N 5M8 Canada
        • telephone_number+41 61 688 1111
        • fax_number
        • cell_number+416-930-1484
        • email_addressnadia.walli@roche.com
        • created2023-08-30 17:02:23
        • modified2024-01-03 14:20:06
  • 3(array)
    • Application(array)
      • id1302
      • user_id796
      • trial_status_id2
      • abstract_of_study<p>\n Forma Therapeutics, Inc. (the Sponsor) is developing FT-4202, an oral Pyruvate Kinase Activator for the treatment of sickle cell disease (SCD). SCD is one of the most commonly inherited blood disorders in the world characterized by Vaso-occlusive crises, anemia, stroke and multiple organ damage. Vaso-occlusive crises are the most common presentation of SCD. Vaso-occlusive crises are caused by activation of the endothelial cells, neutrophils, monocytes and platelets by the sickled red blood cells leading to aggregation and adhesion of these cells to one another and to the endothelial cells leading to clot formation and blockage of the microvascular channels. HbSS prevalence is seen to be 1.6% in children 6-35 months (Suchdev PS 2012). In addition to the high prevalence of SCD patients in this area, outpatient and inpatient at the Siaya Referral Hospital shows over 400 sickle cell disease patients within the eligible age bracket are reviewed. As there is no systematic neonatal screening program in most public and private facilities, there are no neonatal prevalence data. Sickle Cell Disease affects 20-25 million of people globally, of which 12-15 million live in Africa. The natural distribution covers a broad belt, including the Mediterranean, western, parts of East and Central Africa, the Middle East, India and South East Asia. It is estimated that 75-85% are children born in Africa where 50-80% of children born with the disease die before the age of 5 years. The Cooperative Study of Sickle Cell Disease study (CSSD) identified that most of the children with sickle cell disease died before their second birthday due to infection and anemia hence the need to identify these patients even before they shown signs of disease. In Sub-Saharan Africa, approximately 240,000 children are born with Sickle Cell. There is paucity of population level data but in general, based on model projections it is estimated that almost 6,000 newborns (one in every 150 newborns) had Sickle Cell in 2010 and this number could rise to over 10,000 (one in every 100 newborns) per year by 2050. In Kenya, the prevalence varies in regions and mimics the malaria endemicity. In the western region it is estimated that as high as 18% of children are born with a Sickle Cell Trait and 4.5% will end up developing SCD7. In the lake region, it is estimated that about 17% children are carriers of the trait with 0.6% having SCD8 while in the coastal region, using inpatient data, almost 1% of inpatient children have SCD and are almost 20 times likely to die compared to admissions of other morbidities9. Movement in search of better livelihoods leads to a wider spread of the areas previously considered endemic zones. (National Guidelines for control and management of SCD in Kenya, April 2020) Despite current standards of care, including hydroxyurea (HU), blood transfusion, and Immunization against infection relevant to SCD like Streptococcal pneumonia, Hemophilus influenza type B and Hepatitis B and supportive care with analgesia, psychosocial support and malaria prophylaxis, patients with SCD continue to suffer serious morbidity and premature mortality. The clinical hypothesis is that PKR activation will reduce the rate of sickle cell polymerization and improve red blood cell (RBC) membrane function, thereby reducing RBC sickling and RBC hemolysis that lead to vascular obstruction and anemia, two hallmarks of SCD pathology. By addressing this underlying mechanism of SCD, FT-4202 has the potential to be a disease-modifying therapy, leading to improved anemia, reduced hemolysis and the potential to reduce the end-organ damage resulting from chronic hemolytic anemia. This study is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study of patients, age 12 to 65 years, with SCD. Initially, participants will be randomized 1:1:1 to one of two dose levels of FT-4202 or placebo (dose determination portion) and one of the two FT-4202 dose levels will be selected for the Phase 3 portion of the study, and randomization of patients becomes 1:1, the selected FT-4202 dose or placebo (efficacy continuation portion). 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 the efficacy of FT-4202 as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate. This study will enroll up to approximately 344 adult and adolescent patients with SCD. It will be conducted at KEMRI-CRDR Siaya.Siaya is expected to enroll a minimum of 30 participants. Enrolment will be on a competitive basis. The results of this study will form a basis for further studies on the usefulness of Etavopivat for SCD treatment. In addition, the results of this study will be important in defining new treatments for management of sickle cell disease. This could have a significant impact on the quality of life of these patients and their caregivers.</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 Forma Therapeutics, Inc. (the Sponsor) is developing a drug called Etavopivat(FT-4202), for the treatment of sickle cell disease (SCD). Sickle Cell Disease, SCD is one of the most common blood disorders in the world passed from one generation to another. It is characterized by painful episodes, low blood level, and multiple organ damage. Painful episodes are the most common manifestation of the disease. Sickle cell disease commonness is seen to be 1.6% in children 6-35 months (Suchdev PS 2012). In addition to the widespread presence of SCD patients in this area, the outpatient and inpatient at the Siaya Referral Hospital shows over 400 sickle cell disease patients within the eligible age bracket are attended to. As there is no systematic screening program for young children less than 1 month in most public and private facilities, there are no data of sickle cell commonness in this age group. Sickle Cell Disease affects 20-25 million of people globally, of which 12-15 million live in Africa. The natural distribution covers a broad belt, including the Mediterranean, western, parts of East and Central Africa, the Middle East, India and South East Asia. It is estimated that 75-85% are children born in Africa where 50-80% of children born with the disease die before the age of 5 years. The Cooperative Study of Sickle Cell Disease study (CSSD) identified that most of the children with sickle cell disease died before their second birthday due to infection and anemia hence the need to identify these patients even before they shown signs of disease. In Sub-Saharan Africa, approximately 240,000 children are born with Sickle Cell. There is paucity of population level data but in general, based on model projections it is estimated that almost 6,000 newborns (one in every 150 newborns) had Sickle Cell in 2010 and this number could rise to over 10,000 (one in every 100 newborns) per year by 2050. In Kenyasickle cell disease commonness varies in regions and imitates malaria commonness. In the Western region it is estimated that as high as 18% of children are born with a Sickle Cell Trait and 4.5% will end up developing SCD. In the lake region, it is estimated that about 17% children are carriers of the trait with 0.6% having SCD while in the coastal region, using data of the admitted patients, almost 1% of children have SCD and are almost 20 times likely to die compared to admissions of other illnesses. Movement in search of better livelihoods leads to a wider spread of the areas previously considered zones with high sickle cell disease burden. (Source; National Guidelines for control and management of SCD in Kenya, April 2020) Despite current standards of medical care of sickle cell patients, including hydroxyurea (HU), blood transfusion, and Immunization against infection relevant to SCD like ‘Streptococcal pneumonia, Hemophilus influenza type B and Hepatitis B’ and supportive care with painkillers, mental and social support and malaria prevention medications, patients with SCD continue to suffer and some die prematurely. The clinical speculation is that ‘PKR activation’ will reduce the rate of sickle cell chain formation and improve red blood cell (RBC) membrane function, thereby reducing the change of red cell to look like sickle and break down that lead to low blood level and blockage of blood vessel, two hallmarks of Sickle Cell disease. By addressing this, FT-4202 has the potential to be an illness-modifying medication, leading to improved blood level, reduced red cell break down and the potential to reduce the organ damage resulting from longstanding low blood level. This study is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study of patients, age 12 to 65 years, with Sickle Cell Disease. Initially, participants will be randomized 1:1:1 to one of two dose levels of FT-4202 or placebo (dose determination portion) and one of the two FT-4202 dose levels will be selected for the Phase 3 portion of the study, and randomization of patients becomes 1:1, the selected FT-4202 dose or placebo (effectiveness continuation portion) The main purpose is to assess the effectiveness of FT-4202 in adolescents and adults with SCD as compared to an inactive drug(Placebo) as measured by improvement in blood level and the rate of pain episodes in a year. This study will enroll up to approximately 344 adult and adolescent patients with Sickle Cell Disease, SCD. It will be conducted at KEMRI-CRDR Siaya. Siaya is expected to enroll a minimum of 30 participants. Enrolment will be on a competitive basis. The results of this study will form a basis for further studies on the usefulness of Etavopivat for SCD treatment. In addition, the results of this study will be important in defining new treatments for management of sickle cell disease. This could have a significant impact on the quality of life of these patients and their caregivers.</p>\n
      • short_titlePRAISE
      • protocol_noECCT/23/08/02
      • version_no2.0
      • date_of_protocol15-10-2020
      • study_drugEtavopivat (FT-4202)
      • disease_conditionSickle Cell Disease
      • 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_applicant0724522474
      • declaration_date130-08-2023
      • declaration_principal_investigatorDr. Videlis Nduba
      • declaration_date230-08-2023
      • 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 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 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 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_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyDose Response
      • 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 SITE CAPACITY 22 Aug 2023</p>\n<p>\n Number of staff, names, qualifications, experience -- including study co-ordinators, site facilities, emergency facilities, other relevant infrastructure</p>\n<p>\n 1. KEMRI/CRDR, Siaya Site is a modern research facility located in Siaya County within Siaya County Referral Hospital Grounds at KEMRI/CRDR Siaya Site Research Annex. It has a site lab that is well-equipped for sample collection and processing. The site pharmacy is well-equipped for IP management. The equipment is well maintained, regularly checked and calibrated.</p>\n<p>\n 2. The Site has experienced study staff responsible for running the project activities. The staff includes; The Principal Investigator, 2 Medical Officers, 2 Pharmacists, 2 Pharmaceutical technologists, 6 Nurses,6 Quality Assurance Officers / Quality Control Officer, 4 Clinical Officers, 4 Data personnel, 4 lab technologists, 2 administrative Officers, and 7 Community Liaison Officers.</p>\n<p>\n The site study staff are well trained on respective requirements; All staff have done GCP and Ethics training, Lab- IATA and GCLP training.</p>\n<p>\n Site facilities:</p>\n<p>\n 1. 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 Not Applicable</p>\n
      • other_details_regulatory_approved<p>\n Nigeria, KSA, Oman</p>\n
      • other_details_regulatory_rejected<p>\n NA</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration104 Weeks
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • 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
      • 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_states9
      • number_of_sites4
      • multi_country_listNigeria, Ghana, Egypt, Turkey, Kenya, USA, Spain, Russia, Oman
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNot Competitive
      • 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\n\n
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameNduba
      • investigator1_middle_name
      • investigator1_family_nameVidelis
      • investigator1_qualificationMBChB
      • investigator1_professional_addressP.O Box 254 Nairobi Kenya
      • investigator1_telephone0724522474
      • investigator1_emailvnduba@kemri.com
      • organisations_transferred_Yes
      • number_participants30
      • notification<p>\n This Protocol has been submitted to PPB with the attached documents from 3 sites and all the sites have received their approval from ECCT of PPB. This is the 4th site to be submitted.</p>\n
      • approval_date18-10-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted30-08-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-01-14 22:04:19
      • created2023-08-30 09:32:40
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id959
        • application_id1302
        • given_nameNduba
        • middle_name
        • family_nameVidelis
        • qualificationMBChB
        • professional_addressP.O Box 254 Nairobi Kenya
        • telephone0724522474
        • emailvnduba@kemri.com
        • created2023-08-30 10:28:20
        • modified2023-08-30 15:45:23
    • SiteDetail(array)
      • 0(array)
        • id1576
        • application_id1302
        • county_id47
        • site_nameGetrudes Children Hospital
        • physical_address34 MUTHAIGA ROAD, NAIROBI
        • contact_detailsP.O Box 42325- 00100, +254718311709
        • contact_personProf. Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2023-08-30 10:28:20
        • modified2023-08-30 15:45:23
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1577
        • application_id1302
        • county_id41
        • site_nameKEMRI/CRDR
        • physical_addressKemri Clinical Research Annex Siaya County Referral Hospital Grounds, Siaya
        • contact_details0724522474
        • contact_person Dr. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-08-30 12:23:57
        • modified2023-08-30 15:45:23
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 2(array)
        • id1578
        • application_id1302
        • county_id42
        • site_nameKombewa CRC
        • physical_addressP.O. Box 54-40100, Kombew, Kisumu
        • contact_details254 721 996988/ +254 733333530
        • contact_person Dr. Oyieko
        • site_capacity(null)
        • misc(null)
        • created2023-08-30 12:23:57
        • modified2023-08-30 15:45:23
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 3(array)
        • id1579
        • application_id1302
        • county_id42
        • site_nameKondele Childrens Hospital
        • physical_addressJaramogi Oginga Odinga Teaching and Referral Hospital
        • contact_details254-733-812613
        • contact_personDr. Ogutu Benhards
        • site_capacity(null)
        • misc(null)
        • created2023-08-30 12:23:57
        • modified2023-08-30 15:45:23
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id687
        • application_id1302
        • sponsorForma Therapeutics, Inc
        • sponsor_typeIndustry
        • contact_person
        • address500 Arsenal Street, Suite 100 Watertown, MA 02742 617-679-1970
        • telephone_number617-880-9574
        • fax_number
        • cell_number617-880-9574
        • email_address4202medicalmonitor@formatherapeutics.com
        • created2023-08-30 10:28:20
        • modified2023-08-30 15:45:23
  • 4(array)
    • Application(array)
      • id1294
      • user_id693
      • trial_status_id6
      • abstract_of_study<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong><u>STUDY RATIONALE</u></strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The purpose of this study is to assess the efficacy and safety of astegolimab compared with placebo in participants with chronic obstructive pulmonary disease (COPD) who are former or current smokers and have a history of frequent exacerbations. </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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <strong><u>OBJECTIVES AND ENDPOINTS</u></strong></div>\n <div>\n Primary and selected secondary objectives for the study are expressed using the estimand framework in accordance with the International Conference on  harmonization E9 (R1) statistical principles for clinical trials (FDA 2020) in Section 3. The objectives include (but are not limited to) the evaluation of the efficacy and safety of astegolimab compared with placebo.</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 <strong><u>OVERALL DESIGN</u></strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of astegolimab in combination with standard of care (SOC) compared with placebo in combination with SOC, in participants with COPD who are former or current smokers and have a history of frequent exacerbations.  Approximately 1290 participants with COPD are expected to be enrolled globally.</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Following a screening period of at least 7 days and to up to 4 weeks, participants will be randomized in a 1:1:1 ratio to 1 of 3 treatment arms to receive blinded treatment with either astegolimab or placebo.  Randomization will be stratified by smoking status at screening (former smoker vs. current smoker) and region.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The first dose of study drug (astegolimab or placebo) will be administered on Day 1; treatment will continue through Week 50, followed by a 12-week safety follow-up period.  The treatment regimens for each arm are as follows: </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Astegolimab 476 mg SC every 2 weeks (Q2W)</li>\n <li style=\"line-height: 20px;\">\n Astegolimab 476 mg SC every 4 weeks (Q4W) </li>\n </ul>\n <div>\n To ensure that all study participants undergo the same visit schedule, participants randomized to the Q4W dosing arm will alternate between injections of astegolimab and placebo Q2W (beginning with astegolimab on Day 1), thus receiving astegolimab Q4W.</div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Placebo SC Q2W </li>\n </ul>\n <div>\n Participants will return to the clinic Q2W through the treatment completion visit at Week 52.  The primary endpoint analyses will be conducted using the 52-week treatment period data for all participants. </div>\n <div>\n  </div>\n <div>\n <div>\n Several key aspects of the study design and study population are summarized below.  </div>\n <table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 576px;\" width=\"576\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Phase:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Phase </em><em>3</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Type:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Adult patients of any gender</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Control Method:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Placebo</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Diagnosis or Condition:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Chronic obstructive pulmonary disease</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Interventional Model:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Parallel group</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Age:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>40</em><em>-</em><em>80</em><em> years</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Test Compound{s}:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Astegolimab</em></p>\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Site Distribution:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Multi-site and multi-region</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Active Comparator:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Not applicable</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Study Intervention Assignment Method:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Randomization and stratification</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Number of Arms:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>3</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Number of Participants to Be Enrolled:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Approximately 1290 participants</em></p>\n <div>\n  </div>\n </td>\n </tr>\n </tbody>\n </table>\n </div>\n</div>\n<p>\n  </p>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>STUDY TREATMENT</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Astegolimab and placebo will be supplied by the Sponsor as a sterile liquid in 2.25 mL pre-filled syringes with a needle safety device, providing 238 mg/1.7 mL of astegolimab or placebo. </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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Study drug administration must occur after all other procedures have been completed at the visit, unless specifically indicated otherwise.  Study drug will be administered by trained medical personnel.</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Each dose of study drug (astegolimab or placebo) will be administered as 2 SC injections (for a total of 3.4 mL), with each injection administered on a different side of the abdomen (i.e., right or left).  All participants will be observed for at least 30 minutes after each dose and longer (approximately 60 minutes) in the event of an injection-site reaction, as determined by the investigator.  If a participant develops any signs or symptoms to suggest a systemic hypersensitivity reaction or anaphylactic event, longer observation may be warranted as per the opinion of the investigator.</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n There must be a minimum of 8 days between doses. In the event a dosing visit would occur within 8 days of a subsequent or previous dosing visit (e.g., due to an out-of-window visit), the study drug may not be administered. Instead, the next dose of study drug should be administered at the subsequent scheduled visit within the protocol-defined visit window to ensure that the 8-day minimum dosing interval is maintained.</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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>DURATION OF PARTICIPATION</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The total duration of study participation for each individual is expected to be approximately 15 months. </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<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n ----</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Q2W = every 2 weeks; Q4W =  every 4 weeks; SOC = Standard of Care; SC = Subcutaneous</div>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE</span></p>\n
      • laymans_summary<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by irreversible changes in air flow causing progressive obstruction. The prevalence of diagnosed COPD has dramatically increased over recent years and is among the leading causes of disabilities and mortality. The airflow obstruction among COPD patients is largely linked with long-term morbidity and comorbidities such as hypertension, diabetes, ischemic heart disease, stroke, and heart failures were reported in patients with exacerbated COPD cases. These comorbidities are often linked with smoking, systemic inflammation, airflow limitation, and aging.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n These comorbidities do not only negatively impact the patients’ quality of life but also lower their survival rate. Although cigarette smoking is traditionally known as the predominant cause of COPD, there have been increasing cases of non-smokers being diagnosed with the disease. COPD is more prevalent among the older population, with the rising prevalence and mortality among women than male, attributed from increased population of female smokers.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Other risk factors include occupational exposure to chemical fumes, air pollution, childhood infection, and genetic heredity. Spirometry is regarded as the gold standard diagnostic tool for COPD which can detect COPD at early, asymptomatic stages. There is no cure for COPD, however, there are availability of therapies that can improve symptoms and a patients’ quality of life. Despite the treatment advances, there is still an unmet need for improved pharmacological intervention against COPD, particularly in the reduction of exacerbations and modifying the disease progression.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Astegolimab is a drug that is under development for the treatment of patients with COPD. This study will focus on finding out if astegolimab is safe and if it works in comparison to placebo as a treatment for COPD patients who are current or former smokers with a history of frequent exacerbations.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n If found to be efficacious, participants will be given access to the study drug in an Open Label Extension study (GB43374) subject to approval by relevant health authorities.</p>\n
      • short_titleARNASA
      • protocol_noECCT/23/08/01
      • version_no4
      • date_of_protocol20-06-2023
      • study_drugAstegolimab (RO7187807)
      • disease_conditionChronic obstructive pulmonary disease (COPD)
      • 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_nameAstegolimab (RO7187807)
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressPPDSubmissionsMembers.SM@ppd.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_applicantArinda Eloff
      • declaration_date107-08-2023
      • declaration_principal_investigatorDr Teresa Kinyari
      • declaration_date207-08-2023
      • placebo_presentYes
      • study_objectives<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The study objectives are listed below:</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate the safety of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To characterize the astegolimab PK profile </li>\n <li style=\"line-height: 20px;\">\n To evaluate the immune response to astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential relationships between selected covariates and exposure to astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate the safety of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential relationships between drug exposure and the efficacy and safety of astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential effects of ADAs </li>\n <li style=\"line-height: 20px;\">\n To identify and/or evaluate biomarkers that are predictive of response to astegolimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), can provide evidence of astegolimab activity (i.e., PD  iomarkers), or can increase the knowledge and understanding of disease biology and drug safety or pharmacokinetics </li>\n <li style=\"line-height: 20px;\">\n To evaluate health status utility scores of participants treated with astegolimab compared with placebo</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Able and willing to provide written informed consent and to comply with the study protocol</li>\n <li style=\"line-height: 20px;\">\n Age 40-80 years at Visit 1</li>\n <li style=\"line-height: 20px;\">\n Documented COPD diagnosis for <u>></u> 12 months prior to Visit 1</li>\n <li style=\"line-height: 20px;\">\n History of frequent exacerbations, defined as having had 2 or more moderate or severe COPD exacerbations within 12 months prior to Visit 1</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnoea, sputum volume, and sputum purulence) that lead to treatment with systemic corticosteroids (oral, IV, or intramuscular [IM]) and/or antibiotics.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Prior use of antibiotics alone does not qualify as a moderate exacerbation unless the use was specifically for the treatment of worsening symptoms of COPD.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration 24 hours) or lead to death.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"5\">\n Post-bronchodilator FEV1 <u>></u>20% and <80% of predicted at Visit 1 or Visit 2</li>\n <li style=\"line-height: 20px;\" value=\"6\">\n Post-bronchodilator FEV1/FVC < 0.70 at Visit 1 or Visit 2</li>\n <li style=\"line-height: 20px;\" value=\"7\">\n mMRC score <u>></u>2 at screening</li>\n <li style=\"line-height: 20px;\" value=\"8\">\n Current tobacco smoker or former smoker (having stopped smoking for at least 6 months prior to Visit 1) with a history of smoking <u>></u> 10 pack-years (e.g., 20 cigarettes/day for 10 years) At Visit 1, participants who meet the protocol definition of current smoker will receive smoking cessation counselling</li>\n <li style=\"line-height: 20px;\" value=\"9\">\n On optimized COPD maintenance therapy as defined below for <u>></u> 12 months prior to Visit 1.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – Inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – Long-acting muscarinic antagonist (LAMA) plus LABA</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – ICS plus LAMA plus LABA Participants must be stable on current medications and doses for at least 4 weeks prior to Visit 1.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Initiation of new COPD therapy, including a methylxanthine preparation, maintenance macrolide therapy, and/or phosphodiesterase 4 (PDE4) inhibitor is not permitted within 4 weeks prior to Visit 1.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"10\">\n Chest X-ray or computed tomography (CT) scan within 6 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 2) that confirms the absence of clinically significant lung disease besides COPD</li>\n <li style=\"line-height: 20px;\" value=\"11\">\n Demonstrated ability to use and comply with electronic diary (eDiary) requirements, defined as completion of all questions on at least 5 of 7 days prior to Visit 2 Participants unable to demonstrate compliance with the eDiary during the screening period will be screen failed. Participants will have the opportunity to demonstrate eDiary compliance if re-screened (see Protocol Version 2 dated 09 Nov 2022 Section 8.3.3.3).</li>\n <li style=\"line-height: 20px;\" value=\"12\">\n For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Female participants must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 12 weeks after the final dose of astegolimab.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state ( 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a female participant with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Examples of contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"13\">\n For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, as defined below:</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n With a female partner of childbearing potential or pregnant female partner, male participants must remain abstinent or use a condom during the treatment period and for 12 weeks after the final dose of astegolimab to avoid exposing the embryo. Male participants must refrain from donating sperm during this same period.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.</p>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Potential participants are excluded from the study if any of the following criteria apply:</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the study drug</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"2\">\n Any prior treatment with astegolimab</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"3\">\n Current documented diagnosis of asthma</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"4\">\n History of clinically significant pulmonary disease other than COPD</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"5\">\n Diagnosis of alpha-1-antitrypsin deficiency</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"6\">\n History of long-term treatment with oxygen at > 4.0 litres/minute While breathing supplemental oxygen, the participant should demonstrate an oxyhemoglobin saturation of <u>></u> 89%.</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"7\">\n Lung volume reduction surgery or procedure within 12 months prior to Visit 1</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"8\">\n Individuals participating in, or scheduled for, an intensive COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible)</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"9\">\n History of lung transplant</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"10\">\n Any infection that resulted in hospital admission for <u>></u>24 hours and/or treatment with oral, IV, or IM antibiotics within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"11\">\n Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"12\">\n Treatment with oral, IV, or IM corticosteroids (>10 mg/day prednisolone or equivalent) within 4 weeks prior to initiation of study drug</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"13\">\n Treatment with investigational therapy within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"14\">\n Treatment with a licensed biologic agent (e.g., omalizumab, dupilumab, and/or anti-IL-5 therapies) within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"15\">\n Initiation of or change in non-biologic immunomodulatory or immunosuppressive therapy within 3 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"16\">\n Treatment that is considered palliative (e.g., for life expectancy < 12 months)  </li>\n <li style=\"line-height: 20px;\" value=\"17\">\n Planned surgical intervention during the study</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"18\">\n Receipt of a live attenuated vaccine within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"19\">\n Known immunodeficiency, including but not limited to, HIV infection</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"20\">\n Known evidence of active or untreated latent tuberculosis</li>\n <li style=\"line-height: 20px;\" value=\"21\">\n AST, ALT, or total bilirubin elevation <u>></u> 2.0 X the upper limit of normal (ULN) during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"22\">\n Substance abuse, as determined by the investigator, within 12 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"23\">\n History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate > 90%), such as adequately treated carcinoma in situ of the cervix non-melanoma skin carcinoma, localized prostate cancer, or ductal carcinoma in situ</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"24\">\n Any other serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant’s safe participation in and completion of the study</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"25\">\n Unstable cardiac disease, myocardial infarction, or New York Heart Association Class III or IV heart failure within 12 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"26\">\n History or presence of an abnormal ECG that is deemed clinically significant by the investigator, including complete left bundle branch block or second- or third-degree atrioventricular heart block</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"27\">\n QT interval corrected through use of Fridericia’s formula (QTcF) >450 ms if the participant is male or QTcF >470 ms if the participant is female for male or female participants with QRS > 120: QTcF > 480 ms.</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"28\">\n History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, significant left ventricular hypertrophy with strain), or family history of sudden unexplained death or long QT syndrome</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"29\">\n Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of astegolimab</li>\n</ol>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Endpoint</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The primary efficacy objective for this study is to evaluate the efficacy of astegolimab compared with placebo in the mITT population on the basis of the following endpoint:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) that lead to treatment (duration <u>></u> 3 days) with systemic corticosteroids (oral, IV, or IM) at a dose of > 10 mg/day prednisolone equivalent and/or antibiotics.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration > 24 hours) or lead to death.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <em>Primary Estimand</em></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The <em>primary</em> estimand is defined <em>as follows</em>:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Population:  </u></em><em>Participants with COPD who are former or current smokers and have a history of frequent exacerbations, as defined by the inclusion and exclusion criteria (see Sections </em><em>5.1</em><em>and </em><em>5.2</em><em>, respectively)</em><em>, and received at least one </em><em>dose of study drug (mITT population)</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Variable:  </u></em><em>annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Treatments:</u></em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em>Experimental: astegolimab Q2W</em></li>\n <li style=\"line-height: 20px;\">\n <em>Experimental: astegolimab Q4W</em></li>\n <li style=\"line-height: 20px;\">\n <em>Control: placebo</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Intercurrent events</u></em><em>:</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em>Early</em><em> discontinuation from study treatment</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Handling of intercurrent events</u></em><em>:  A treatment policy with regards to the intercurrent events listed above will be applied for the primary analysis</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Summary measure</u></em><em>:  rate ratio (RR) for annualized rate of moderate and severe COPD exacerbations</em></li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Endpoints</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The secondary efficacy objective for this study is to evaluate the efficacy of astegolimab compared with placebo in the mITT population on the basis of the following endpoints:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Time to first moderate or severe COPD exacerbation during the 52-week treatment period</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in HRQoL at Week 52, as assessed through the SGRQ-C total score</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in post-bronchodilator FEV<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">1</span> (liters) at Week 52</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in E‑RS:COPD total score at Week 52</li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with improvement in HRQoL, defined as a decrease from baseline of <u>></u> 4 points in SGRQ-C total score, at Week 52</li>\n <li style=\"line-height: 20px;\">\n Annualized rate of severe COPD exacerbations over the 52-week treatment period</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The secondary endpoints will be analyzed in the mITT population<em>.  Time-to-event endpoints will be analyzed using log-rank test and Cox proportional hazards regression models. Continous endponts will be summarized by treatment arm and timepoints, and analyzed using mixed models for repeated measures.  Improvement in HRQoL will be summarized as proportion of responders, i.e., patients achieving pre-specified improvement, and analyzed using logistic regression models.  </em></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Seconday and Exploratory Endpoints are the following:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the safety of astegolimab compared with placebo</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: </p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Incidence and severity of all TEAEs, including SAEs, AESIs, and TEAEs leading to death or discontinuation</li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n TEAEs severity will be determined according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (HHS 2017) (hereafter referred to as the DAIDS Toxicity Grading Scale), with slight modifications for clarity and for alignment with internal practices (see Appendix 8) </div>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Change from baseline in selected vital signs </li>\n <li style=\"line-height: 20px;\">\n Change from baseline in selected clinical laboratory test results and ECGs </li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To characterize the astegolimab PK profile </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: Serum concentration of astegolimab at specified timepoints</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the immune response to astegolimab </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: Prevalence of ADAs at baseline and incidence of ADAs during the study</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the efficacy of astegolimab compared with placebo </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Change in COPD symptoms as measured by the E-RS:COPD total score at Week 24  </li>\n <li style=\"line-height: 20px;\">\n Change in E-RS:COPD individual domain scores (breathlessness, cough and sputum, and chest symptoms) from baseline at Week 24 and 52 </li>\n <li style=\"line-height: 20px;\">\n Change in EXACT individual domain scores (tired or weak, sleep disturbance, and scared or worried) from baseline at Week 24 and 52 </li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with HRQoL improvement, defined as a decrease from baseline of <u>></u> 4 points in SGRQ-C total score, at Week 12 and Week 24 </li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with symptom improvement, defined as a decrease of <u>></u> 2 points from baseline in E-RS:COPD total score, at Week 24 and Week 52 </li>\n <li style=\"line-height: 20px;\">\n bsolute change from baseline in post-bronchodilator</li>\n <li style=\"line-height: 20px;\">\n FEV1 (liters) at Weeks 12, 24, and 36 </li>\n <li style=\"line-height: 20px;\">\n Annualized rate of moderate COPD exacerbations over the 52-week treatment period </li>\n <li style=\"line-height: 20px;\">\n Duration of hospital stay for severe COPD exacerbations </li>\n <li style=\"line-height: 20px;\">\n Proportion of severe COPD exacerbations requiring hospital readmission within 30 days </li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in daily step count at Weeks 12, 24, and 52 </li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in time in moderate and vigorous physical activity at Weeks 12, 24, and 52 </li>\n </ul>\n</div>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Obective: To evaluate potential relationships between drug exposure and the efficacy and safety of astegolimab</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Relationship between serum concentration or PK parameters for astegolimab and efficacy endpoints</li>\n <li style=\"line-height: 20px;\">\n Relationship between serum concentration or PK parameters for astegolimab and safety endpoints </li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate potential relationships between selected covariates and exposure to astegolimab </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Relationship between selected covariates and serum concentration or PK parameters for astegolimab</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate potential effects of ADAs</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Relationship between ADA status and efficacy, safety, PK or biomarker endpoints</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To identify and/or evaluate biomarkers that are predictive of response to astegolimab (i.e., predictive biomarkers), are early surrogates of efficacy, are</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n associated with progression to a more severe disease state (i.e., prognostic biomarkers), can provide evidence of astegolimab activity (i.e., PD biomarkers), or can</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n increase the knowledge and understanding of disease biology and drug safety or pharmacokinetics </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint:  Relationship between biomarkers in blood, plasma, and serum and efficacy, safety, PK, immunogenicity, or other biomarker endpoints </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate health status utility scores of participants treated with astegolimab compared with placebo</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Change from baseline in EuroQol EQ-5D-5Lindex-based and VAS scores at Week 52</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic1
      • 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 The study site is the University of Nairobi Clinical Research Centre (UNCRC) located in the Department of Human Anatomy and Medical Physiology at the Chiromo Campus of the University of Nairobi Faculty of Health Sciences. In this location administrative and archiving facilities are domiciled. The clinic facilities will be physical located in the KNH RIDU and laboratory facilities will be at the KAVI ICR. Recruitment, consenting, randomization and administration of IMP will be at the RIDU unit the chest clinic number 17.</p>\n<div>\n The research medical records unit, administrative offices, storage of the IP, laboratory testing and specimen packaging for shipping will be done at the KAVI ICR . which is well-staffed by trained personnel with expertise in the following research related tasks: Clinical officers: Participate in screening of potential patients based on the inclusion and exclusion criteria. \n <div>\n  Clinical Research Nurses: Obtain Informed consents, Make CRF entries/resolve queries; Collect medical information; Vital signs; Collect adverse events; Administer IP; Collect lab samples; Participant recruitment and retention. Pharmacist and Pharmacy Technologist: Investigational Drug Services: Manage IP receipt/return; Prepare and dispense IP; Unbinding procedures. \n <div>\n Regulatory Affairs: Manage submissions to ethics and regulatory authorities. Maintain essential documents and ensure compliance Contracts and Budgets: Maintain legal and financial documents; Ensure appropriate invoicing to the sponsor; Ensure appropriate processes for research covered procedures versus patients’ standard of care Data Management: Make CRF entries/resolve queries; Maintain the patients’ research documents Clinical Research operations: Oversight of UNCRC studies and staff; support all research staff with their tasks Investigators: Obtain Informed Consent; Assess eligibility; Make CRF entries/resolve Queries; Medical decisions/review; Collect medical information; Vital signs; Assess 8 Ordinal Scale; Collect/Assess Adverse Events; Administer IP; Conduct Physical Exam; Collect Lab Samples; Maintain Essential Documents; IP processes The KNH Chest Clinic is part of the Respiratory Infectious Disease Unit (RIDU). \n <div>\n The facility is designed to provide an integrated, patient-centered service across the care cycle from diagnosis, treatment, surveillance and palliative care. \n <div>\n  The ambulatory chest clinic also offers streamlined, efficient care by a multidisciplinary team of respiratory specialists. \n <div>\n This coordinated approach provides comprehensive care and support for patients with lung disease and their caregivers. \n <div>\n  All patients treated at the KNH Respiratory Infectious Disease Unit (RIDU) will have access to smoking cessation, psychosocial and support counseling as well as palliative care support as part of best practice. This is not limited to non-study patients and thus is available to study patients as well. The UNCRC provides an approach to care which is guided by international standards including accreditation by the Kenya Medical Laboratory Technician and Technologist Board (KMLLTB) and IATA Shipping and Transport of Regulated Biologic Material certification.</div>\n </div>\n </div>\n </div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Switzerland is the host country and Sponsor intends to submit study for approval in the host country</span></p>\n
      • other_details_regulatory_notapproved<table itemprop=\"copy-paste-table\">\n <tbody>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Country</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Status</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Submission Date</strong></span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Australia</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">19-May-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">China</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">25-May-2023</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">India</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">10-May-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">New Zealand</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">20-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Philippines</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">04-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Taiwan, Province of China</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">20-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Thailand</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">27-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Argentina</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Brazil</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">15-Mar-2023 / 20Mar2023</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Chile</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">23-May-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Mexico</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">02-May-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Switzerland</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">06-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Turkey</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">23-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">United Kingdom</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">13-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Austria</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Belgium</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Bulgaria</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Czech Republic</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Denmark</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">France</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Germany</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Greece</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Hungary</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Italy</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Latvia</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Netherlands</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Poland</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Romania</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Spain</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Sweden</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"> </span></p>\n
      • other_details_regulatory_approved<p>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"> </span></p>\n<table itemprop=\"copy-paste-table\">\n <tbody>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Country</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Name of Regulatory Authority</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Approval date</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Number of Sites</strong></span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">United States of America </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">The United States Food and Drug Administration </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">18 November 2022 </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">74</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Canada </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Health Canada </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">19 April 2023</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">10</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">South Africa</span></p>\n </td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">SAHPRA</span></td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">11 May 2023</span></td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">8</span></td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Korea</span></p>\n </td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">MFDA</span></td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">18 April 2023</span></td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">10</span></td>\n </tr>\n </tbody>\n</table>\n<p>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"> </span></p>\n
      • other_details_regulatory_rejected<p>\n Not applicable. None of the Regulatory Authorities or Ethics Committees have rejected this trial</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_durationThe total duration of study participation for each individual is expected to be approximately 15 months.
      • 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_states39
      • number_of_sitesApproximately 6 sites will participate in Kenya. As approvals from the Local Ethics Committees (LECs) are obtained to avoid delays in site-activation as each site submits to their LEC at different timepoints.
      • multi_country_listChin ; Hong Kong; India; Korea, Republic of; New Zealand; Philippines; Taiwan, Province of China; Thailand; Vietnam; Argentina; Brazil; Chile; Mexico; Canada; United States; Egypt; Israel; Kenya; South Africa; Switzerland; Turkey; United Kingdom; Austria; Belgium; Bulgaria; Czech Republic; Denmark; France; Germany; Greece; Hungary; Italy; Latvia; Netherlands; Poland; Romania; Spain; Sweden; Australia
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNo maximum nor minimum enrolment per site as enrolment is competitive worldwide, but it is expected that approximately 2 - 3 participants will participate per site.
      • total_participants_worldwideApproximately 1290 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_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • 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_nameProfessor Videlis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressKenyatta National Hospital Grounds, Off Hospital Road, Behind Government Chemist, P.O. BOX 47855-00100, Nairobi, Kenya
      • investigator1_telephone+254790484654
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participantsEnrolment is competitive worldwide. Approximately 12 participants will participate in Kenya.
      • notification<p>\n N/A</p>\n
      • approval_date06-12-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-01-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApproved after satisfactory response to reviewer 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)
      • modified2025-05-07 15:38:23
      • created2023-07-19 09:16:00
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id953
        • application_id1294
        • given_nameDr Teresa
        • middle_name
        • family_nameKinyari
        • qualificationMedical Doctor
        • professional_addressKenyatta National Hospital Respiratory Disease Unit Prof Mungai Road Off Wasawo Drive Off Riverside Drive Chiromo Campus University Of Nairobi P.O. Box 19676 00202 Nairobi Kenya
        • telephone+254 707028067
        • emailKinyari Teresa Mwendwa <tmwendwa@uonbi.ac.ke>
        • created2023-07-19 12:07:46
        • modified2024-01-03 14:21:03
    • SiteDetail(array)
      • 0(array)
        • id1564
        • application_id1294
        • county_id47
        • site_nameUniversity of Nairobi Clinical Research Centre
        • physical_addressProf Mungai Road Off Wasawo Drive Off Riverside Drive Chiromo Campus University Of Nairobi P.O. Box 19676 00202 Nairobi Kenya
        • contact_details+254 707028067
        • contact_personDr Teresa Kinyari
        • site_capacity(null)
        • misc(null)
        • created2023-07-19 12:07:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1565
        • application_id1294
        • county_id47
        • site_nameCenter for Research In Tropical Medicine and Community Development
        • physical_addressP.O. Box 6387, Thika, Kenya
        • contact_details+254722425613
        • contact_personDr Jesse Gitaka
        • site_capacity(null)
        • misc(null)
        • created2023-07-19 13:02:58
        • modified2024-01-03 14:21:03
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1566
        • application_id1294
        • county_id16
        • site_nameClinical Research Health Network (CREA-N)
        • physical_addressMachakos Level 5 Hospital Site P.O. Box 19 -90100 Machakos Kenya
        • contact_details+254115021107
        • contact_personDr Jacqueline Mirera
        • site_capacity(null)
        • misc(null)
        • created2023-07-19 14:32:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
      • 3(array)
        • id1567
        • application_id1294
        • county_id41
        • site_nameKEMRI-CRDR Siaya Clinical Research Annex
        • physical_addressSiaya County Referral Hospital Grounds, P.O. BOX 40600-144, Siaya, Kenya
        • contact_details+254700111395 / +254731141831
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-07-19 14:32:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 4(array)
        • id1568
        • application_id1294
        • county_id3
        • site_nameKEMRI-Mtwapa Clinical Annex
        • physical_addressP.O. Box 428-80108, Mtwapa
        • contact_details+254722523370
        • contact_personDr Mary Matilu
        • site_capacity(null)
        • misc(null)
        • created2023-07-19 14:32:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 5(array)
        • id1569
        • application_id1294
        • county_id47
        • site_nameKEMRI-CRDR Clinical Research Annex
        • physical_addressKenyatta National Hospital Grounds, Off Hospital Road, Behind Government Chemist, P.O. BOX 47855-00100, Nairobi, Kenya
        • contact_details+254790484654
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-07-19 14:32:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id683
        • application_id1294
        • sponsorF. Hoffmann-La Roche Ltd
        • sponsor_typeIndustry
        • contact_personNadia Walli
        • addressClinical Research (PDG - CCO, North America),7070 Mississauga Road Mississauga, ON L5N 5M8 Canada
        • telephone_number+41 61 688 1111
        • fax_number
        • cell_number+416-930-1484
        • email_addressnadia.walli@roche.com
        • created2023-07-19 12:07:46
        • modified2024-01-03 14:21:03
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • trial_therapeutic_confirmatory1
• $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