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  • 1Recruiting
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• applications(array)
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    • Application(array)
      • id1295
      • user_id796
      • trial_status_id2
      • abstract_of_study<p>\n Sickle cell disease is a chronic hemolytic anemia caused by inheritance of a mutated form of hemoglobin (Hb), sickle Hb (HbS). The disease is characterized by polymerization of HbS in RBCs when in the deoxygenated state, resulting in a sickle-shaped deformation of RBCs. Sickled cells aggregate in capillaries precipitating vaso-occlusive events that generally present as acute and painful crises (VOC) resulting in tissue ischemia, infarction, and long-term tissue damage, that underlies the significant morbidity and increased mortality associated with this disease. Red blood cells in SCD patients tend to be fragile due to sickling and other factors, and the mechanical trauma of circulation causes hemolysis and chronic anemia. Sickle cell disease is the most common inherited hemolytic anemia, affecting approximately 100,000 individuals in the United States (US) (CDC 2020), approximately 35,000 to 164,000 individuals in Europe, and millions more worldwide (Hassell, 2010; Lobitz et al, 2018). In Kenya, Ministry of Heath estimates that at least 6000 children are born annually with SCD. The paediatric to adult ratio stands at 3:1 and Sickle Cell disease has been found to be more prevalent in areas with high prevalence of Malaria in Kenya (Williams et al., 2005). Kombewa lies in the area with high prevalence of Malaria. Therapeutic treatment of SCD remains inadequate. Potentially curative therapies, such as bone marrow transplant or gene therapies are invasive and such high-risk procedures are available to only a limited number of patients. For most patients, treatment involves supportive care for management of vaso-occlusive crisis (VOC) or the use of hydroxyurea (HU), to stimulate production of fetal Hb (HbF) and reduce Hb polymerization. However, the myelosuppressive and teratogen effects of HU limit its effectiveness. More recently other therapies have been approved; L-Glutamine to reduce the acute complications of SCD, Volexotor, indicated to reduce hemolysis and improve hemoglobin levels, and Crizanlizumab to reduce the incidence of VOCs. None of these therapies results in both improvement of anemia and a reduction in the frequency of VOCs. Additional therapies that target the underlying physiology are needed. Pyruvate kinase R (PKR) is the isoform of Pyruvate kinase expressed in RBCs and its activation is proposed to directly target both sickling by reducing deoxy-HbS and Hemolysis by improving RBC membrane integrity. The study drug, Etavopivat (FT-4202) is a potent selective activator of PKR. This is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study among SCD patients, aged 12 to 65 years. The primary objective is to assess the efficacy of FT- 4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb) and annualized vaso-occlusive crisis (VOC) rate. The Phase 2, is the dose determination portion and the selected dose will be assessed in Phase 3, the efficacy portion against placebo. Following a double blind period of 52 weeks, all patients may enter a 52-week open-label extension period. The study will enroll approximately 344 adult and adolescent patients with SCD, who fulfill the eligibility criteria (60 to 90 patients in the Dose Determination Group and approximately 274 patients in the Efficacy Continuation Group). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. Study activities during visits will include but not limited to a physical, vital signs, randomization, 12-Lead ECG, and various laboratory assessments at screening and as part of efficacy and safety assessments at time points as per the protocol Schedule. Patients will be evaluated for safety by collection of adverse events (AEs)/serious adverse events (SAEs), laboratory tests and vital signs. Serious adverse events will be collected from the time of signature of informed consent throughout the dosingperiod and including the follow-up period. Ethical approvals will be sought from the relevant authorities prior to study implementation. Results from the overall study will inform the potential usefulness of FT-4202 in the treatment of patients with SCD.</p>\n
      • study_title<p>\n An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)</p>\n
      • laymans_summary<p>\n Sickle cell disease (SCD) is an blood disease that causes the Red blood cells in blood to (RBCs) to change to sickle shape. Sickled cells do not flow easily through small blood vessels and may cause obstruction resulting in recurrent episodes of pain. These episodes are referred to as vaso-occlusive events (VOC). The sickled cells have a shorter life span than the non sickled cells and this results in low blood levels (anaemia). SCD affects about 100,000 patients in the United States, up to 164,000 patients in Europe, and millions more in the rest of the world. In Kenya, the Ministry of Health estimates that at least 6000 children are born with SCD every year. Sickle Cell disease patients are found in larger numbers in areas with where Malaria common than in areas where malaria is less common in Kenya (Williams et al., 2005). Kombewa lies in an area where Malaria is common. Cure for SCD can be achieved by procedures called bone marrow transplant or gene therapies, but these are not available or possible for all patients and are also expensive. For most patients treatment is mainly supportive; pain control, blood transfusions or the use of hydroxyurea (HU). Newer treatments have been developed that increase blood level or reduce frequency of VOCs but none of the treatments does both. The search for other treatmentsis on going. The study drug, Etavopivat (FT- 4202) is a potent activator of a protein called Pyruvate kinase R (PKR), which is key in the process of generating energy in the body. It is that PKR activation will reduce the rate of RBC sickling and RBC destruction leading to less frequent episodes of pain(VOC) and increased blood levels. This study is designed to take place in phases among patients with SCD, aged 12 to 65 years. The phase 2 is the dose determination portion when patients will receive one of two dose levels of study drug or placebo (a placebo is a substance that looks like the study drug but has no effects on the body). The selected dose will be assessed for efficacy (effectiveness) in Phase 3, for increasing blood level and reducing episodes of VOC, over 52 weeks, when compared to a placebo (). After the 52 week follow up period the patients may enter 52 weeks period in which all patients receive the study drug. This study will enroll up to about 344 patients with SCD (60 to 90 patients in the Dose Determination Group and 274 patients in the Phase 3). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. At study pre-determined time points, the participants will undergo heath assessments; physical examinations, taking of vital signs (e.g. temperature, Blood pressure, heart rate, respiratory rate), recording heart activity using an electrocardiogram (ECG), and various laboratory assessments as part of follow up safety assessments. All the information will be recorded and then analyzed. Ethical approvals will be sought from the relevant authorities prior to study start. Results from the overall study will inform on the potential usefulness of the study drug (FT-4202) in the treatment of patients with SCD</p>\n
      • short_titlePRAISE
      • protocol_noECCT/23/07/04
      • version_no2.0
      • date_of_protocol15-10-2020
      • study_drugFT-4202
      • disease_conditionSickle Cell
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameFT-4202
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmctafrica.regarchive@mct-cro.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
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      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
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      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
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      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicant0721996988
      • declaration_date121-07-2023
      • declaration_principal_investigatorNA
      • declaration_date221-07-2023
      • placebo_presentYes
      • study_objectives<p>\n 1. 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 2.To assess the efficacy of FT-4202 as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate.</p>\n<p>\n <strong>Secondary Efficacy Objectives ·</strong></p>\n<p>\n To measure the effects of FT-4202 on clinical measures and sequelae of hemolysis ·</p>\n<p>\n To evaluate the effects of FT-4202 on the sequelae of VOC ·</p>\n<p>\n To assess changes in fatigue of sickle cell patients taking FT-4202</p>\n
      • principal_inclusion_criteria<p>\n Eligibility for inclusion will be determined on the basis of diagnosis SCD genetic type, age of 12 to 65 years and at least 2 VOCs in the last12 months prior to providing informed assent/consent. For the itemized list of Inclusion criteria please refer to the main study protocol, Section 5.1 titled “Inclusion Criteria”.</p>\n<p>\n  </p>\n<p>\n Inclusion Criteria Participants are eligible to be included in the study only if all the following criteria apply:</p>\n<p>\n 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)</p>\n<p>\n Age 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 Exclusion Criteria Patients are excluded from the study if they meet any of the following criteria:</p>\n<p>\n 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 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</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</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_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyTherapeutic exploratory and Confirmatory
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Kombewa Clinical Research Centre Site Capacity 25 Mar 2023 There are 35 health facilities within the Kombewa Clinical Research Centre catchment area out of which 6 can hospitalize. Kombewa County Hospital is the referral point for all the facilities in Seme sub-County, while Chulaimbo is the referral facility in Kisumu West County. The patients are referred to Jaramogi Oginga Odinga Teaching and referral hospital, Avenue Hospital, and other private facilities within Kisumu city in case of an emergency. The unit has the following staff to support research studies; 2 paedricians, 3 medical offices, 5 clinical offices, 1 regulatory officer, 6 study coordinators,7 laboratory technologist, 9 nurses, 1 pharmacist, 2 pharmaceutical technologist, 8 data clerks and 38 filed workers. The unit has two storey building consisting of office space, laboratory which includes clinical, immunology and microbiology labs, clinical rooms, emergency room, observation room, pharmacy, records storage area and archives.</p>\n
      • other_details_explanation<p>\n NA</p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n Oman: Turkey: KSA: Nigeria, USA</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n NA</p>\n
      • estimated_duration104 Weeks
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overYes
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo Controlled
      • 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_states10
      • number_of_sites4
      • multi_country_listNigeria, Ghana, Egypt, Turkey, Kenya, USA, KSA, Spain, Oman, Russia
      • data_monitoring_committeeYes
      • total_enrolment_per_site30
      • total_participants_worldwide344
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyParticipant under the age of 18
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJanet
      • investigator1_middle_nameN
      • investigator1_family_nameOyieko
      • investigator1_qualificationMedical Officer
      • investigator1_professional_addressP.o Box Kombewa
      • investigator1_telephone0721996988
      • investigator1_emailjanet.oyieko@usamru-k.org
      • organisations_transferred_Yes
      • number_participants30
      • notification<p>\n None</p>\n
      • approval_date28-08-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted21-07-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewers have provided approval for the protocol.
      • final_report(null)
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      • quantity_imported(null)
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      • quantity_destroyed(null)
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      • balance_site(null)
      • final_date(null)
      • modified2025-01-14 22:20:12
      • created2023-07-21 10:46:54
      • total_sites(null)
      • ecitizen_invoice(null)
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      • 0(array)
        • id954
        • application_id1295
        • given_nameDr. Janet
        • middle_name
        • family_nameOyieko
        • qualificationMedical Officer
        • professional_addressP.O Box 54 Kisumu
        • telephone0721996988
        • emailjanet.oyieko@usamru-k.org
        • created2023-07-21 10:59:42
        • modified2023-07-21 20:38:31
    • SiteDetail(array)
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        • id1570
        • application_id1295
        • county_id42
        • site_nameKondele Children\'s Hospital Center for Clinical Research (CCR),
        • physical_addressJaramogi Oginga Odinga Teaching and Referral Hospital
        • contact_detailsP.O Box Jaramogi Oginga Odinga Teaching and Referral Hospital
        • contact_personDr. Ogutu
        • site_capacity(null)
        • misc(null)
        • created2023-07-21 10:59:42
        • modified2023-07-21 20:38:31
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1571
        • application_id1295
        • county_id47
        • site_nameGertrude\'s Children Hospital
        • physical_address34 MUTHAIGA ROAD,
        • contact_detailsNAIROBI P.O. BOX 42325 - 00100 NAIROBI, KENYA
        • contact_personProf. J. Githanga
        • site_capacity(null)
        • misc(null)
        • created2023-07-21 12:35:56
        • modified2023-07-21 20:38:31
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1572
        • application_id1295
        • county_id41
        • site_nameKEMRI/CRDR Kemri Clinical Research Annex
        • physical_addressSiaya County Referral Hospital Grounds, Siaya
        • contact_details0724522474
        • contact_personDr. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-07-21 12:35:56
        • modified2023-07-21 20:38:31
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id684
        • application_id1295
        • sponsorForma Therapeutics
        • sponsor_typeIndustry
        • contact_personDanish Khan
        • address500 Arsenal Street, Suite 100 Watertown, MA 02742
        • telephone_number617-679-1970
        • fax_number
        • cell_number617-880-9574
        • email_addressmedicalmonitor@formatherapeutics.com
        • created2023-07-21 10:59:42
        • modified2023-07-21 20:38:31
  • 1(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
  • 2(array)
    • Application(array)
      • id1209
      • user_id796
      • trial_status_id1
      • abstract_of_study<p>\n Sickle cell disease is a chronic hemolytic anemia caused by inheritance of a mutated form of hemoglobin (Hb), sickle Hb (HbS). The disease is characterized by polymerization of HbS in RBCs when in the deoxygenated state, resulting in a sickle-shaped deformation of RBCs. Sickled cells aggregate in capillaries precipitating vaso-occlusive events that generally present as acute and painful crises (VOC) resulting in tissue ischemia, infarction, and long-term tissue damage, that underlies the significant morbidity and increased mortality associated with this disease. Red blood cells in SCD patients tend to be fragile due to sickling and other factors, and the mechanical trauma of circulation causes hemolysis and chronic anemia. Sickle cell disease is the most common inherited hemolytic anemia, affecting approximately 100,000 individuals in the United States (US) (CDC 2020), approximately 35,000 to 164,000 individuals in Europe, and millions more worldwide (Hassell, 2010; Lobitz et al, 2018). In Kenya, Ministry of Heath estimates that at least 6000 children are born annually with SCD. The paediatric to adult ratio stands at 3:1 and Sickle Cell disease has been found to be more prevalent in areas with high prevalence of Malaria in Kenya (Williams et al., 2005). Kombewa lies in the area with high prevalence of Malaria. Therapeutic treatment of SCD remains inadequate. Potentially curative therapies, such as bone marrow transplant or gene therapies are invasive and such high-risk procedures are available to only a limited number of patients. For most patients, treatment involves supportive care for management of vaso-occlusive crisis (VOC) or the use of hydroxyurea (HU), to stimulate production of fetal Hb (HbF) and reduce Hb polymerization. However, the myelosuppressive and teratogen effects of HU limit its effectiveness. More recently other therapies have been approved; L-Glutamine to reduce the acute complications of SCD, Volexotor, indicated to reduce hemolysis and improve hemoglobin levels, and Crizanlizumab to reduce the incidence of VOCs. None of these therapies results in both improvement of anemia and a reduction in the frequency of VOCs. Additional therapies that target the underlying physiology are needed. Pyruvate kinase R (PKR) is the isoform of Pyruvate kinase expressed in RBCs and its activation is proposed to directly target both sickling by reducing deoxy-HbS and Hemolysis by improving RBC membrane integrity. The study drug, Etavopivat (FT-4202) is a potent selective activator of PKR. This is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study among SCD patients, aged 12 to 65 years. The primary objective is to assess the efficacy of FT-4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb) and annualized vaso-occlusive crisis (VOC) rate. The Phase 2, is the dose determination portion and the selected dose will be assessed in Phase 3, the efficacy portion against placebo. Following a double blind period of 52 weeks, all patients may enter a 52-week open-label extension period. The study will enroll approximately 344 adult and adolescent patients with SCD, who fulfill the eligibility criteria (60 to 90 patients in the Dose Determination Group and approximately 274 patients in the Efficacy Continuation Group). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. Study activities during visits will include but not limited to a physical, vital signs, randomization, 12-Lead ECG, and various laboratory assessments at screening and as part of efficacy and safety assessments at time points as per the protocol Schedule. Patients will be evaluated for safety by collection of adverse events (AEs)/serious adverse events (SAEs), laboratory tests and vital signs. Serious adverse events will be collected from the time of signature of informed consent throughout the dosingperiod and including the follow-up period. Ethical approvals will be sought from the relevant authorities prior to study implementation. Results from the overall study will inform the potential usefulness of FT-4202 in the treatment of patients with SCD.</p>\n
      • study_title<p>\n An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)</p>\n
      • laymans_summary<p>\n Sickle cell disease (SCD) is an blood disease that causes the Red blood cells in blood to (RBCs) to change to sickle shape. Sickled cells do not flow easily through small blood vessels and may cause obstruction resulting in recurrent episodes of pain. These episodes are referred to as vaso-occlusive events (VOC). The sickled cells have a shorter life span than the non sickled cells and this results in low blood levels (anaemia). SCD affects about 100,000 patients in the United States, up to 164,000 patients in Europe, and millions more in the rest of the world. In Kenya, the Ministry of Health estimates that at least 6000 children are born with SCD every year. Sickle Cell disease patients are found in larger numbers in areas with where Malaria common than in areas where malaria is less common in Kenya (Williams et al., 2005). Kombewa lies in an area where Malaria is common. Cure for SCD can be achieved by procedures called bone marrow transplant or gene therapies, but these are not available or possible for all patients and are also expensive. For most patients treatment is mainly supportive; pain control, blood transfusions or the use of hydroxyurea (HU). Newer treatments have been developed that increase blood level or reduce frequency of VOCs but none of the treatments does both. The search for other treatmentsis on going. The study drug, Etavopivat (FT-4202) is a potent activator of a protein called Pyruvate kinase R (PKR), which is key in the process of generating energy in the body. It is that PKR activation will reduce the rate of RBC sickling and RBC destruction leading to less frequent episodes of pain(VOC) and increased blood levels. This study is designed to take place in phases among patients with SCD, aged 12 to 65 years. The phase 2 is the dose determination portion when patients will receive one of two dose levels of study drug or placebo (a placebo is a substance that looks like the study drug but has no effects on the body). The selected dose will be assessed for efficacy (effectiveness) in Phase 3, for increasing blood level and reducing episodes of VOC, over 52 weeks, when compared to a placebo (). After the 52 week follow up period the patients may enter 52 weeks period in which all patients receive the study drug. This study will enroll up to about 344 patients with SCD (60 to 90 patients in the Dose Determination Group and 274 patients in the Phase 3). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. At study pre-determined time points, the participants will undergo heath assessments; physical examinations, taking of vital signs (e.g. temperature, Blood pressure, heart rate, respiratory rate), recording heart activity using an electrocardiogram (ECG), and various laboratory assessments as part of follow up safety assessments. All the information will be recorded and then analyzed. Ethical approvals will be sought from the relevant authorities prior to study start. Results from the overall study will inform on the potential usefulness of the study drug (FT-4202) in the treatment of patients with SCD</p>\n
      • short_titlePRAISE
      • protocol_noECCT/23/01/02
      • version_no2.0
      • date_of_protocol15-10-2020
      • study_drugFT-4202
      • disease_conditionSickle Cell
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameFT 4202
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmctafrica.regarchive@mct-cro.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantOgutu Bernhards Ragama
      • declaration_date119-01-2023
      • declaration_principal_investigatorOgutu Bernhards Ragama
      • declaration_date219-01-2023
      • placebo_presentYes
      • study_objectives<p>\n To assess the efficacy of FT-4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb)</p>\n<p>\n To assess the efficacy of FT-4202 as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate</p>\n<p>\n To measure the effects of FT-4202 on clinical measures and sequelae of hemolysis</p>\n<p>\n To evaluate the effects of FT-4202 on the sequelae of VOC</p>\n<p>\n To assess changes in fatigue of sickle cell patients taking FT-4202</p>\n<p>\n To measure additional effects of FT-4202 on clinical measures and sequelae of hemolysis</p>\n<p>\n To evaluate the duration of improvement in Hb from FT-4202</p>\n<p>\n To evaluate additional effects of FT-4202 on transfusion use •</p>\n<p>\n To evaluate the effects of FT-4202 on hospitalization</p>\n<p>\n To evaluate the effects of FT-4202 on types and duration of VOC</p>\n<p>\n To evaluate the effects of FT-4202 on opioid usage</p>\n
      • principal_inclusion_criteria<p>\n PRINCIPAL INCLUSION CRITERIA * Participants are eligible to be included in the study only if all the following criteria apply: Informed Consent</p>\n<p>\n 1. Patient has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each patient; in the case of adolescent patients, both the consent of the patient’s legal representative or legal guardian, and the patient’s assent must be obtained) Age</p>\n<p>\n 2. Age 12 to 65 years, inclusive, at time of randomization Type of Participant and Disease Characteristics</p>\n<p>\n 3. Patient has a confirmed diagnosis of sickle cell disease • Documentation of SCD genotype (HbSS, HbSβ0 -thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing; if unavailable, must be confirmed by laboratory testing during screening</p>\n<p>\n 4. Patient has had at least 2 episodes of VOC in the past 12 months • For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis (for which there was no explanation other than VOC) which required prescription or healthcare professional-instructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening)</p>\n<p>\n 5. Hemoglobin ≥ 5.5 and ≤ 10 g/dL (≥ 55 and ≤ 100 g/L) during screening</p>\n<p>\n 6. For participants taking HU, the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study, in the opinion of the Investigator Sex and Contraceptive/Barrier Requirements</p>\n<p>\n 7. Patients, who if female and of child bearing potential, are using highly effective methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug</p>\n
      • principal_exclusion_criteria<p>\n PRINCIPAL EXCLUSION CRITERIA * Medical Conditions</p>\n<p>\n 1. More than 10 VOCs (as defined in Inclusion Criterion 4) within the past 12 months</p>\n<p>\n 2. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF</p>\n<p>\n 3. Female who is breast feeding or pregnant</p>\n<p>\n 4. Hepatic dysfunction characterized by: • Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) • Direct bilirubin > 3.0 × ULN</p>\n<p>\n 5. Patients with clinically significant bacterial, fungal, parasitic, or viral infection requiring systemic therapy • Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening/enrollment until active therapy has been completed Note: Infection prophylaxis is allowed (see concomitant medication restrictions)</p>\n<p>\n 6. Known human immunodeficiency virus (HIV) positivity</p>\n<p>\n 7. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and and hepatitis B core antibody [HepBcAb] positive)</p>\n<p>\n 8. Active hepatitis C infection</p>\n<p>\n 9. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory < 30 mL/min/1.73 m2 ) or on chronic dialysis</p>\n<p>\n 10. History of malignancy within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation • Patients with malignancy considered surgically cured are eligible (eg, nonmelanoma skin cancer, cancer of the cervix in-situ, ductal carcinoma in situ [stage 1], grade 1 endometrial cancer)</p>\n<p>\n 11. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following: • Unstable angina pectoris or myocardial infarction or elective coronary intervention • Congestive heart failure requiring hospitalization • Uncontrolled clinically significant arrhythmias • Symptomatic pulmonary hypertension hepatitis B core antibody [HepBcAb] positive)</p>\n<p>\n 12. History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage</p>\n<p>\n 13. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)</p>\n<p>\n 14. Patients with iron deficiency (eg, serum iron less than the lower limit of normal [LLN] or ferritin <10 µg/L) who are not taking or are unable to take iron supplements at the time of consent and during the study</p>\n<p>\n 15. Patients with folate (or folic acid or Vitamin B9) or Vitamin B12 deficiency (eg, folate or Vitamin B12 levels less than the LLN) who are not taking or are unable to take supplements before the first dose of study drug and during the study</p>\n<p>\n 16. Patients who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended Prior/Concomitant Therapy</p>\n<p>\n 17. Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) • Patients who have received an RBC transfusion for any reason within 60 days of the Screening period are eligible if HbA (adult Hb) < 10% by Hb electrophoresis before start of study treatment</p>\n<p>\n 18. Receiving or use of concomitant medications that are strong inducers or moderate/strong inhibitors of CYP3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study</p>\n<p>\n 19. Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study</p>\n<p>\n 20. Use of a selectin antagonist (eg, crizanlizumab or other monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study</p>\n<p>\n 21. Use of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study</p>\n<p>\n 22. Receipt of prior cellular-based therapy (eg, hematopoietic cell transplant, gene modification therapy) Prior/Concurrent Clinical Study Experience</p>\n<p>\n 23. Participated in another clinical trial of an investigational agent (or medical device) within 28 days or 5 half-lives of first dose of study drug, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device) Other Exclusions</p>\n<p>\n 24. Inadequate venous access as determined by the Investigator/ site staff</p>\n<p>\n 25. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent</p>\n
      • primary_end_points<p>\n Hb response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period</p>\n<p>\n Annualized VOC rate during the 52-week blinded treatment period based on adjudicated VOC review</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n  Principal Investigator Dr. Bernhards Ogutu MBChB, Mmed(Paed), PhD 30 years</p>\n<p>\n Sub-Investigator Dr Godfrey Allan Otieno MBChB, Mmed(Paed) 20 years</p>\n<p>\n Sub-Investigator Dr John Orimbo Guda MBChB 2 years</p>\n<p>\n Sub-Investigator Dr Fredrick Olewe MBChB 5 years</p>\n<p>\n Pharmacist Ruth Ongoro Wasuna Bpharm, MBA 20 years</p>\n<p>\n Study Coordinator Ishmael Osoo Sports BScN 15 years</p>\n<p>\n Lab Technologist Pretvine Okello Diploma Lab Sciences 2 years</p>\n<p>\n Lab Technologist Linah Achieng Oluoch Diploma Lab Sciences 2 years</p>\n<p>\n Study Nurse Jane Olum Higher Diploma in Nursing 15 years</p>\n<p>\n Study Nurse Oliver Akach Diploma Nursing 3 years</p>\n<p>\n Study Clinician Nashon Okello Diploma Clinical Medicine 2 years</p>\n<p>\n Field Assistant Pamela Atieno Diploma Community Development 2 years</p>\n<p>\n Field Assistant Caroline Atieno Certificate Computers Applications 2 year</p>\n<p>\n Data Entry clerk Nerea Omondi Diploma Community Development 20 years</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>Site facilities</strong></p>\n<p>\n <strong>1. </strong>Laboratory</p>\n<p>\n 2. Pharmacy</p>\n<p>\n 3. Emergency center and facilities</p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n Oman: Turkey: KSA:</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n NA</p>\n
      • estimated_duration104 Weeks
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo Controlled
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states8
      • number_of_sites4
      • multi_country_listOman, KSA, Nigeria, Ghana, Egypt, Turkey, Kenya, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNot competitive enrolment
      • total_participants_worldwide344
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyParticipant under the age of 18
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameOgutu Ragama
      • investigator1_middle_nameBernhards
      • investigator1_family_nameRagama
      • investigator1_qualificationMMED Paeds
      • investigator1_professional_addressP. O. Box 2254 Nairobi or P.O. Box 54, Kisumu
      • investigator1_telephone+254-35-22942/254-733-812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants30
      • notification
      • approval_date24-05-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted24-01-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed conclusively.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-16 16:39:57
      • created2023-01-18 10:02:32
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id881
        • application_id1209
        • given_nameOgutu
        • middle_nameBernhards
        • family_nameRagama
        • qualificationMMED Paeds
        • professional_addressP. O. Box 2254 Nairobi or P.O. Box 54, Kisumu
        • telephone+254-35-22942/254-733-812613
        • emailogutu6@gmail.com
        • created2023-01-18 11:07:53
        • modified2023-01-24 11:41:35
    • SiteDetail(array)
      • 0(array)
        • id1389
        • application_id1209
        • county_id42
        • site_nameKondele Children\'s Hospital Center for Clinical Research (CCR),
        • physical_addressP.O Box 54-40100 PO Box 54-40100 Kisumu,
        • contact_details254-733-812613
        • contact_personDr. Ogutu Bernhards
        • site_capacity(null)
        • misc(null)
        • created2023-01-18 11:07:53
        • modified2023-01-24 11:41:35
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1390
        • application_id1209
        • county_id47
        • site_nameGertrude\'s Children Hospital
        • physical_address 34 MUTHAIGA ROAD, NAIROBI
        • contact_detailsPO BOX 42325- 00100, +254718311709.
        • contact_personProf. Githanga Jessie
        • site_capacity(null)
        • misc(null)
        • created2023-01-18 12:48:26
        • modified2023-01-24 11:41:35
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1391
        • application_id1209
        • county_id41
        • site_nameKEMRI/CRDR Kemri Clinical Research Annex Siaya County Referral Hospital Grounds,
        • physical_address Siaya County Referral Hospital Grounds
        • contact_details0724522474
        • contact_personDr. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-01-18 12:48:26
        • modified2023-01-24 11:41:35
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
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      • 3(array)
        • id1392
        • application_id1209
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        • site_nameKombewa CRC
        • physical_addressP.O. Box 54-40100, Kisumu, Kenya
        • contact_detailsTel: +254 721 996988/ +254 733333530
        • contact_personDr. Oyieko
        • site_capacity(null)
        • misc(null)
        • created2023-01-18 12:48:26
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        • County(array)
          • id42
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          • created2012-06-15 10:27:02
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    • Sponsor(array)
      • 0(array)
        • id628
        • application_id1209
        • sponsorForma Therapeutics, Inc.
        • sponsor_typeOthers
        • contact_personDanish Khan
        • address500 Arsenal Street, Suite 100 Watertown, MA 02742
        • telephone_number617-679-1970
        • fax_number
        • cell_number617-880-9574
        • email_address4202medicalmonitor@formatherapeutics.com
        • created2023-01-18 11:07:53
        • modified2023-01-24 11:41:35
  • 3(array)
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      • user_id796
      • trial_status_id1
      • abstract_of_study<p>\n Sickle cell disease is a chronic hemolytic anemia caused by inheritance of a mutated form of hemoglobin (Hb), sickle Hb (HbS). The disease is characterized by polymerization of HbS in RBCs when in the deoxygenated state, resulting in a sickle-shaped deformation of RBCs. Sickled cells aggregate in capillaries precipitating vaso-occlusive events that generally present as acute and painful crises (VOC) resulting in tissue ischemia, infarction, and long-term tissue damage, that underlies the significant morbidity and increased mortality associated with this disease. Red blood cells in SCD patients tend to be fragile due to sickling and other factors, and the mechanical trauma of circulation causes hemolysis and chronic anemia. Sickle cell disease is the most common inherited hemolytic anemia, affecting approximately 100,000 individuals in the United States (US) (CDC 2020), approximately 35,000 to 164,000 individuals in Europe, and millions more worldwide (Hassell, 2010; Lobitz et al, 2018). In Kenya, Ministry of Heath estimates that at least 6000 children are born annually with SCD. The paediatric to adult ratio stands at 3:1 and Sickle Cell disease has been found to be more prevalent in areas with high prevalence of Malaria in Kenya (Williams et al., 2005). Kombewa lies in the area with high prevalence of Malaria. Therapeutic treatment of SCD remains inadequate. Potentially curative therapies, such as bone marrow transplant or gene therapies are invasive and such high-risk procedures are available to only a limited number of patients. For most patients, treatment involves supportive care for management of vaso-occlusive crisis (VOC) or the use of hydroxyurea (HU), to stimulate production of fetal Hb (HbF) and reduce Hb polymerization. However, the myelosuppressive and teratogen effects of HU limit its effectiveness. More recently other therapies have been approved; L-Glutamine to reduce the acute complications of SCD, Volexotor, indicated to reduce hemolysis and improve hemoglobin levels, and Crizanlizumab to reduce the incidence of VOCs. None of these therapies results in both improvement of anemia and a reduction in the frequency of VOCs. Additional therapies that target the underlying physiology are needed. Pyruvate kinase R (PKR) is the isoform of Pyruvate kinase expressed in RBCs and its activation is proposed to directly target both sickling by reducing deoxy-HbS and Hemolysis by improving RBC membrane integrity. The study drug, Etavopivat (FT-4202) is a potent selective activator of PKR. This is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study among SCD patients, aged 12 to 65 years. The primary objective is to assess the efficacy of FT- 4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb) and annualized vaso-occlusive crisis (VOC) rate. The Phase 2, is the dose determination portion and the selected dose will be assessed in Phase 3, the efficacy portion against placebo. Following a double blind period of 52 weeks, all patients may enter a 52-week open-label extension period. The study will enroll approximately 344 adult and adolescent patients with SCD, who fulfill the eligibility criteria (60 to 90 patients in the Dose Determination Group and approximately 274 patients in the Efficacy Continuation Group). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. Study activities during visits will include but not limited to a physical, vital signs, randomization, 12-Lead ECG, and various laboratory assessments at screening and as part of efficacy and safety assessments at time points as per the protocol Schedule. Patients will be evaluated for safety by collection of adverse events (AEs)/serious adverse events (SAEs), laboratory tests and vital signs. Serious adverse events will be collected from the time of signature of informed consent throughout the dosingperiod and including the follow-up period. Ethical approvals will be sought from the relevant authorities prior to study implementation. Results from the overall study will inform the potential usefulness of FT-4202 in the treatment of patients with SCD.</p>\n
      • study_title<p>\n An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)</p>\n
      • laymans_summary<p>\n Sickle cell disease (SCD) is an blood disease that causes the Red blood cells in blood to (RBCs) to change to sickle shape. Sickled cells do not flow easily through small blood vessels and may cause obstruction resulting in recurrent episodes of pain. These episodes are referred to as vaso-occlusive events (VOC). The sickled cells have a shorter life span than the non sickled cells and this results in low blood levels (anaemia). SCD affects about 100,000 patients in the United States, up to 164,000 patients in Europe, and millions more in the rest of the world. In Kenya, the Ministry of Health estimates that at least 6000 children are born with SCD every year. Sickle Cell disease patients are found in larger numbers in areas with where Malaria common than in areas where malaria is less common in Kenya (Williams et al., 2005). Kombewa lies in an area where Malaria is common. Cure for SCD can be achieved by procedures called bone marrow transplant or gene therapies, but these are not available or possible for all patients and are also expensive. For most patients treatment is mainly supportive; pain control, blood transfusions or the use of hydroxyurea (HU). Newer treatments have been developed that increase blood level or reduce frequency of VOCs but none of the treatments does both. The search for other treatmentsis on going. The study drug, Etavopivat (FT- 4202) is a potent activator of a protein called Pyruvate kinase R (PKR), which is key in the process of generating energy in the body. It is that PKR activation will reduce the rate of RBC sickling and RBC destruction leading to less frequent episodes of pain(VOC) and increased blood levels. This study is designed to take place in phases among patients with SCD, aged 12 to 65 years. The phase 2 is the dose determination portion when patients will receive one of two dose levels of study drug or placebo (a placebo is a substance that looks like the study drug but has no effects on the body). The selected dose will be assessed for efficacy (effectiveness) in Phase 3, for increasing blood level and reducing episodes of VOC, over 52 weeks, when compared to a placebo (). After the 52 week follow up period the patients may enter 52 weeks period in which all patients receive the study drug. This study will enroll up to about 344 patients with SCD (60 to 90 patients in the Dose Determination Group and 274 patients in the Phase 3). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. At study pre-determined time points, the participants will undergo heath assessments; physical examinations, taking of vital signs (e.g. temperature, Blood pressure, heart rate, respiratory rate), recording heart activity using an electrocardiogram (ECG), and various laboratory assessments as part of follow up safety assessments. All the information will be recorded and then analyzed. Ethical approvals will be sought from the relevant authorities prior to study start. Results from the overall study will inform on the potential usefulness of the study drug (FT-4202) in the treatment of patients with SCD</p>\n
      • short_titlePRAISE
      • protocol_noECCT/23/01/03
      • version_no2.0
      • date_of_protocol15-10-2020
      • study_drugFT-4202
      • disease_conditionSickle Cell
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameFT-4202
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmctafrica.regarchive@mct-cro.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantJessie Nyokabi Githanga
      • declaration_date124-01-2023
      • declaration_principal_investigatorJessie Nyokabi Githanga
      • declaration_date224-01-2023
      • placebo_presentYes
      • study_objectives<p>\n To assess the efficacy of FT-4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb)</p>\n<p>\n To assess the efficacy of FT-4202 as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate</p>\n<p>\n To measure the effects of FT-4202 on clinical measures and sequelae of hemolysis</p>\n<p>\n To evaluate the effects of FT-4202 on the sequelae of VOC</p>\n<p>\n To assess changes in fatigue of sickle cell patients taking FT-4202</p>\n<p>\n To measure additional effects of FT-4202 on clinical measures and sequelae of hemolysis</p>\n<p>\n To evaluate the duration of improvement in Hb from FT-4202 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 *</p>\n<p>\n 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_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • 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 Number of staff, names, qualifications, experience -- including study co-ordinators, site facilities, emergency facilities, other relevant infrastructure.</p>\n<p>\n  </p>\n<p>\n <strong>Site staff designation Name Qualifications Years of experience</strong></p>\n<p>\n <strong>Principal Investigator:</strong> Prof. Jessie Githanga Master of Medicine in Pathology, One-year post-graduate fellowship in cytogenetics and haematology at the Health Sciences Centre, University of Manitoba, Winnipeg, Canada. This was under a Canadian International Development Agency (CIDA) program 21 YEARS</p>\n<p>\n <strong>Co-Investigator/main coordinator</strong> Dr. Doreen Karimi Mutua Masters in Medicine (Pediatrics and Child Health), Fellowship training in Pediatric hematology/oncology at Jimma University, (Ethiopia) /ASLAN project (USA) 10 years Study</p>\n<p>\n <strong>Doctor/study coordinator</strong> Dr. Hilda Jebet Bachelor in Medicine and Surgery 5 years</p>\n<p>\n <strong>Study Doctor</strong> Dr. David Owera Bachelor in Medicine and Surgery 3 years</p>\n<p>\n <strong>Study Pharmacist</strong> Dr. Samuel Madere Bachelor's degree in Pharmacy 10 years</p>\n<p>\n <strong>Study Pharmacist</strong> Cresencia Nekesa Makokha Diploma in Pharmacy technologist 3 years</p>\n<p>\n <strong>Study Pharmacist</strong> Dr. Winnie Owilla Bachelor's degree in Pharmacy 4 years</p>\n<p>\n <strong>Study nurses</strong> Felicity Kamundi Bachelor's degree in Nursing 10 years</p>\n<p>\n Study nurses Jane Nduati Bachelor's degree in Nursing 3 years</p>\n<p>\n Study nurses Faith Mumbi Bachelor's degree in Nursing 1 years</p>\n<p>\n Logistics Manager Peninah Chege 10 years</p>\n<p>\n Laboratory technician/technologist Charles Muia (technologist) Lead* Bachelor's degree in medical laboratory science 5 years</p>\n<p>\n Laboratory technician/technologist Herman Akumu (technologist) Diploma in laboratory technologist 10 years phlebotomist)</p>\n<p>\n Joseph Langat Certificate in pediatric phlebotomy 10 years</p>\n<p>\n Laboratory technician/technologist Francisca Akinyi Bachelor's degree in medical laboratory science 1 years</p>\n<p>\n Assistant study coordinator Edwina Oboke Bachelor's degree 5 years</p>\n<p>\n Administrative assistant Truphena Otinyo Certificate in receptionist, computer and typing 10 years</p>\n
      • other_details_explanation<p>\n Not applicable</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Oman: Turkey: KSA:</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n NA</p>\n
      • estimated_duration104 weeks
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states8
      • number_of_sites4
      • multi_country_listOman, KSA, Nigeria, Ghana, Egypt, Turkey, Kenya, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNot Competative
      • total_participants_worldwide344
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyParticipant under the age of 18
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJessie
      • investigator1_middle_nameGithanga
      • investigator1_family_nameNyokabi
      • investigator1_qualification MBChB, MMed (Path)(UON), FCPath ECSA Associate Professor
      • investigator1_professional_addressAddress: P. O. Box 19601-00202, Nairobi, Kenya
      • investigator1_telephone+254 721245721
      • investigator1_emailjgithanga3@gmail.com
      • organisations_transferred_Yes
      • number_participantsApproximately
      • notification<p>\n NONE</p>\n
      • approval_date19-06-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted24-01-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed. The application is similar to ECCT/23/01/02
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-02 23:39:40
      • created2023-01-24 13:15:38
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id889
        • application_id1217
        • given_nameGithanga
        • middle_nameGithanga
        • family_nameNyokabi
        • qualification MBChB, MMed (Path)(UON), FCPath ECSA Associate Professor
        • professional_addressAddress: P. O. Box 19601-00202, Nairobi, Kenya
        • telephone+254 721245721
        • emailjgithanga3@gmail.com
        • created2023-01-24 13:34:35
        • modified2023-01-24 23:13:29
    • SiteDetail(array)
      • 0(array)
        • id1418
        • application_id1217
        • county_id47
        • site_nameGertrude\'s Children Hospital
        • physical_address34 MUTHAIGA ROAD, NAIROBI
        • contact_detailsPO BOX 42325- 00100, +254718311709
        • contact_personProf. Githanga Jessie
        • site_capacity(null)
        • misc(null)
        • created2023-01-24 13:34:35
        • modified2023-01-24 23:13:29
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1419
        • application_id1217
        • county_id42
        • site_name Kondele Children\'s Hospital Center for Clinical Research (CCR),
        • physical_addressP.O Box 54-40100 PO Box 54-40100 Kisumu,
        • contact_details254-733-812613
        • contact_personDr. Ogutu Bernhards
        • site_capacity(null)
        • misc(null)
        • created2023-01-24 15:02:58
        • modified2023-01-24 23:13:29
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1420
        • application_id1217
        • county_id41
        • site_nameKEMRI/CRDR Kemri Clinical Research Annex Siaya County Referral Hospital Grounds
        • physical_addressSiaya County Referral Hospital Grounds
        • contact_details 0724522474
        • contact_personDr. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-01-24 15:02:58
        • modified2023-01-24 23:13:29
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 3(array)
        • id1421
        • application_id1217
        • county_id42
        • site_nameKombewa CRC
        • physical_addressP.O. Box 54-40100, Kisumu, Kenya
        • contact_detailsTel: +254 721 996988/ +254 733333530
        • contact_personDr. Oyieko
        • site_capacity(null)
        • misc(null)
        • created2023-01-24 15:02:58
        • modified2023-01-24 23:13:29
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id634
        • application_id1217
        • sponsorForma Therapeutics, Inc.
        • sponsor_typeOthers
        • contact_personDanish Khan
        • address500 Arsenal Street, Suite 100 Watertown, MA 02742
        • telephone_number617-679-1970
        • fax_numberNA
        • cell_number617-880-9574
        • email_address4202medicalmonitor@formatherapeutics.com
        • created2023-01-24 13:34:35
        • modified2023-01-24 23:13:29
  • 4(array)
    • Application(array)
      • id1079
      • user_id71
      • trial_status_id3
      • abstract_of_study<p>\n Summary Background: WHO helps evaluate drugs by randomising their effects on important outcomes. The WHO Solidarity trial involves collaboration between hundreds of hospitals in dozens of countries. It began by evaluating four repurposed drugs, and now guided by an independent Expert Groups, is now evaluating addition to the local Standard of Care of other potential drugs. Simplicity of procedures: Within each country, the national co-ordinator invites selected hospitals and helps them get ethical and regulatory approval and study drugs, then patient recruitment can begin. To facilitate collaboration even in overloaded hospitals, patient enrolment and randomisation (via a cloud-based GCP-compliant platform) and all other trial procedures are greatly simplified, and no paperwork is required. Once consent has been obtained, electronic entry of anonymised details of a few key characteristics of each patient takes only a few minutes. At the end of patient entry, a random treatment allocation is generated. Eligibility: Adults (age ≥ 18 years), hospitalised with laboratory-confirmed COVID, not expecting transfer within 72 hours, and, in the view of their doctors, with no contra-indication to any potentially relevant study drug. Consent: The study website https://data.castoredc.com/studies has printable patient information in some UN official languages. Once the information has been explained to patients, obtaining consent takes only a few minutes. An electronic image of the signature page is kept (or, if national regulations forbid this, a note to file), and the printed information and original consent stays with the patient or legal representative. Data collected electronically immediately before randomisation: • Country, hospital (from a list of approved hospitals) and randomising doctor • Confirmation that informed consent was obtained from the patient (or a surrogate/ representative) Age, sex and (yes/no): smoking, diabetes, heart disease, chronic liver disease, chronic lung disease, asthma, HIV, obesity • Date of onset of symptoms, date of hospitalization, and (yes/no) current/planned use of a few drugs • Respiratory support (highest level currently being given): A. No oxygen, B. Low-flow oxygen, C. High-flow nasal oxygen, D. Non-invasive ventilation, E. Invasive ventilation, F. ECMO • SpO2 (%) and, if not ventilated, respiratory rate • Any major bilateral lung abnormality? (not imaged/no major abnormality/infiltrations/patchy shadowing) • Which relevant study drugs are locally available? (yes/no: artesunate, infliximab, imatinib; confirm that none of these locally available drug(s) is, in the doctor’s view, definitely contra-indicated) Trial entry; randomization: Once electronic data collection has been completed the patient automatically enters the trial and a random allocation of their trial treatment is generated (by an algorithm that ensures eventual balance in the characteristics just recorded between each study drug and its controls) and displayed. The patients will be randomly allocated either to Standard of Care (SoC) or to one of the study drugs. Changing management of study patients: At all times the patient’s medical team remains solely responsible for decisions about that patient’s care and safety. Hence, if the team decides that deviation from the randomly allocated treatment is appropriate for a particular patient, this should be done, regardless of the random allocation. That patient would still be part of the trial, regardless of what treatment they were actually given.   Safety: Any suspected unexpected serious adverse reactions (SUSARs) that are life-threatening must be reported within 24 hours, as must any other possibly related treatment-related serious adverse events (SAEs). Other adverse events do not need to be reported. Follow-up: When patients die or are discharged, follow-up ceases and their outcome is reported, regardless of whether the trial treatment actually got given. The following information is to be entered: • Which study drug(s) got given (and for how long) • Which of a few selected other drugs were given (and for how long) • What respiratory support was given (and first and last dates): A No respiratory support, B Low-flow oxygen, C High-flow nasal oxygen, D Non-invasive ventilation, E Invasive ventilation, F ECMO • Date discharged alive or date of death in hospital and cause of death. • Pregnant? Yes/No/unknown Primary and secondary analyses: Primary analyses: In-hospital mortality in all patients. Major secondary analyses: In-hospital mortality subdivided by initial respiratory support. Further secondary analyses: duration of hospital stay in lower-risk patients (A-B); and in higher-risk patients (C-F); and initiation of ventilation in lower-risk patients. The main safety analyses will be of reported SAEs possibly related to the treatment and SUSARs. Numbers entered: The larger the numbers entered the more accurate the results will be. If substantial numbers get hospitalised in the participating centres, it may be possible to enter several thousand hospitalised patients receiving no oxygen or low-flow supplemental oxygen, and a few thousand receiving high-flow nasal oxygen, ventilation or ECMO, but realistic, appropriate sample sizes will not be estimated at the start of the trial; the numbers that can be entered will depend on the evolution of the epidemic. Heterogeneity: If a study treatment affects outcome, then this effect could well differ between patients who were receiving different levels of respiratory support when randomised, and separate consideration of these is a secondary analysis. Effects could also differ between younger and older patients, or between patients in one or another country or geographic region. If sufficient numbers are randomised, it may be possible to obtain statistically reliable treatment comparisons within each of several different countries/regions or types of patient. Adaptive design: A global Data and Safety Monitoring Committee will keep the accumulating safety results and major outcome results under regular review. The WHO may recommend adding further treatment arms while the trial is in progress, if evidence emerges that there are suitable candidate therapeutics. Conversely, the WHO may decide to discontinue some treatment arms, especially if the Global Data and Safety Monitoring Committee reports, based on interim analyses, that one or other of the trial treatments definitely does or does not affect mortality. Add-on studies: Particular countries, or particular groups of hospitals, may want to collaborate in making further measurements or observations, such as serial virology, serial blood gases or chemistry, serial lung imaging, or serial documentation of other aspects of disease status of trial patients (perhaps through linkage to electronic healthcare records and routine medical databases). These could be thought of as Phase 2b trials that are being conducted concurrently with the Phase 3 trial. However, while well-organised additional research studies of the natural history of the disease or the effects of the trial treatments could well be valuable, they are not core requirements. Data security: Patient information will be encrypted and held securely by the WHO. Those analysing it will use only anonymised data, and no identifiable patient details will appear in publications. Publication: This international collaboration is co-ordinated through the World Health Organisation. Major findings will be disseminated by the WHO and published in the names of the collaborators.</p>\n
      • study_title<p>\n An international randomised trial of additional treatments for COVID-19 in hospitalised patients who are all receiving the local standard of care</p>\n
      • laymans_summary<p>\n We are conducting a study to find out the best treatments for COVID-19. Several medicines for it have been proposed. These medicines may have no effect or a moderate effect on the disease, but none is expected to have a big effect. This hospital is collaborating through the World Health Organization and hospitals in many other countries in a study to help discover whether any of these treatments can help</p>\n
      • short_titleSOLIDARITY TRIAL PLUS
      • protocol_noECCT/21/11/05
      • version_no1.0
      • date_of_protocol05-04-2021
      • study_drugArtesunate, Infliximab:Imatinib
      • disease_conditionCovid-19
      • product_type_biologicals1
      • product_type_proteins1
      • product_type_immunologicals0
      • 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
      • comparatorNo
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      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjnyange@kaviuon.org
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      • applicant_registration_ctr(null)
      • applicant_pan_african1
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      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr Loice Ombajo
      • declaration_date112-11-2021
      • declaration_principal_investigatorDr Loice Ombajo
      • declaration_date212-11-2021
      • placebo_presentNo
      • study_objectives<p>\n The primary outcome is in-hospital mortality from any cause, and the primary analyses are of mortality in all randomised patients. The major secondary outcomes are initiation of ventilation, and duration of hospital stay. The main safety analyses will be of reported SAEs and SUSARs possibly related to the treatment and SUSARs. Numbers of deaths in hospital attributed to causes other than COVID-19 will also be reported. It is not expected that any of the treatments currently being tested will have a large effect on the risk of death, but if any had just a moderate effect and was widely practicable then this could avoid large numbers of deaths. Conversely, demonstration that certain agents have no material effect on major outcomes would be of value. Moderate effects can, however, be reliably demonstrated or refuted only by large-scale randomized evidence.</p>\n
      • principal_inclusion_criteria<p>\n Eligibility o adults (age ≥18 years, which allows consent), o recently hospitalised (or already in hospital) with laboratory-confirmed COVID, o not expected to be transferred within 72 hours, o with, in the view of their doctors, no contra-indication to any potentially relevant study drug.</p>\n
      • principal_exclusion_criteria<p>\n Contraindication to any of the study drugs, expected transfer withing 72 hours of enrollment</p>\n
      • primary_end_points<p>\n This is an open-label randomised controlled trial that will randomise COVID-19 positive patients to either continu-ing local standard of care or enrolling one of three intervention arms: Artesunate, Imatinib or Infliximab. Collated international data will be analysed for mortality and duration of hospital stay and need for ventilatory support</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • 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
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      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n 2. KNH WHO SOLIDARITY TRIAL STUDY SETTING/SITE The KNH-Infectious Disease Unit (IDU) was established in 2014 as part of the response towards the Ebola Virus Disease outbreak in West Africa (2014 to 2017). Some of the health care workers in KNH-IDU served for more than 1 year in the West African Ebola response. The KNH study site has 3 COVID-19 dedicated facilities for the care of COVID-19 patients. These are the KNH-IDU Unit (6-bed ICU facility), the KNH-Mbagathi IDU facility (60-bed facility for the care of COVID-19 patients including 8 HDU beds) and the KNH Day Care Unit (20-bed facility for the management of HCWs who get infected with COVID-19). 2.1. Standard of Care The KNH IDU offers standard of care as per the Interim National Case Management Guidelines. In addition, patients admitted to the units have access to on-site chest radiography/ imaging and laboratory services. Baseline tests (Full blood count, renal and liver biochemistry) are obtained for all admitted patients. Thereafter, repeat tests are done when clinically indicated. 2.2. KNH-IDU Facilities Staff All the KNH-IDU facilities are staffed by a multidisciplinary team of dedicated and experienced HCWs trained in COVID-19 management and infection prevention and control management including safe donning and doffing of PPE. The KNH-IDUs are staffed by a dedicated team of Infectious diseases specialists and fellows, Medical officers, nurses, pharmacists, pharmaceutical technicians, counselors, physiotherapists, laboratory technologists, health information officers, nutritionists, catering and support staff. 2.3. Healthcare Worker Safety All these healthcare workers are trained in infection prevention and control and doffing and donning of PPE. The safety protocols include twice daily temperature monitoring and logging, daily symptomatic screening, buddy system for donning and doffing of PPE and team-work while entering the isolation units. Testing and re-testing of the HCWs will be done as per guidelines in the MOH COVID-19 human resource for health (HRH) protocols. Furthermore, KNH has identified and developed the KNH Day Care Unit as a facility for the care of HCWs who get infected with COVID-19 in the line of duty</p>\n<p>\n 3.0 STAFFING The Nairobi hospital has over 2000 staff members. These are members in both clinical and non-clinical departments and together they ensure the smooth running of the hospital and the highest level of care for the patients. The East wing has staff of all cadres, including doctors (both medical officers and specialists) nurses, physiotherapists, counsellors, occupation therapists and all other non-medical supporting staff. The staff ratios in the covid unit are fluid. We have three permanent consultants employed by the hospital. We also have 3 permanent Senior Registrars in Internal Medicine and 21 permanent medical officers. There is capacity to increase the numbers in the event of a surge of patients. The nurses are such that there is a nursing ratio of 1:1 in the Intensive Care Unit and also enough for the wards to give a comfortable nursing ratio. There is also capacity to increase the numbers of nursing staff depending on patient numbers. We also have physiotherapists and occupational therapist. We have radiologist on call and have a portable Xray and portable ultrasound machine</p>\n
      • other_details_explanation<p>\n No</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration11 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard of Care (SoC)
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      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
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      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
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      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteThis is a global trial, each site will enrol as many patients as it takes to be able to answer the objectives
      • total_participants_worldwideThis is a global trial, each site will enrol as many patients as it takes to be able to answer the objectives
      • 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
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      • investigator1_emailloicea.la@gmail.com
      • organisations_transferred_No
      • number_participantsThis is a global trial, each site will enrol as many patients as it takes to be able to answer the objectives
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      • approval_date13-01-2022
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      • date_submitted12-11-2021
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      • approved_reasonThe queries raised have been addressed conclusively.
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      • final_date(null)
      • modified2024-01-03 15:01:35
      • created2021-11-02 11:46:06
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        • created2021-11-02 11:48:17
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        • contact_personDr. Salami Kolawole
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        • email_addresssalamik@who.int
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