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 (SCD).
- Conditions
- sickle cell disease (SCD)MedDRA version: 21.0Level: PTClassification code: 10040644Term: Sickle cell disease Class: 100000004850Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Registration Number
- CTIS2024-511535-97-00
- Lead Sponsor
- Forma Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 420
1) Provision of consent, 2) Patient has a confirmed diagnosis of sickle cell disease, 3) 2-15 episodes of documented vaso-occlusive crises in the past 12 months, 4) Hemoglobin = 5.5 and = 10.5 g/dL (= 55 and = 105 g/L) during screening, 5) Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 days prior to start of study treatment, 6) Female patients of childbearing potential must use acceptable methods of contraception; male patients are willing to use acceptable methods of contraception, 7)Patients on crizanlizumab or L-glutamine oral powder (Endari®) treatment at the time of consent may be eligible if they: • Have been on a stable dose for = 12 months at the time of consent (i.e., no changes to the dose except for changes to weight or for safety reasons) • Have been = 80% compliant with the planned regimen during the 12 months prior to the time of consent • Meet the VOC eligibility requirement in Inclusion Criterion 4.
Medical Conditions 1) More than 15 vaso-occlusive crises within the past 12 months prior to screening, Prior/Concomitant Therapy 1) Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion), 2) Receiving or use of concomitant medications that are strong inducers of CYP3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study, 3) Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study, 4) Use of an experimental selectin antagonist (e.g., monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study, 5) Uso de eritropoyetina u otro tratamiento con factor de crecimiento hematopoyético dentro de los 28 días posteriores al inicio del tratamiento del estudio o la necesidad anticipada de dichos agentes durante el estudio., 6) Receipt of prior cellular-based therapy (e.g., hematopoietic cell transplant, gene modification therapy), 2) Female who is breast feeding or pregnant, 3) Hepatic dysfunction characterized by: - Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) OR - Direct bilirubin > 3.0 × ULN, 4) Known HIV positive, 5) Active hepatitis B or hepatitis C infection, 6) Severe renal dysfunction or on chronic dialysis, 7) 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, 8) History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage, 9) History of deep venous thrombosis requiring systemic anticoagulation therapy for = 6 weeks, occurring within 6 months prior to Day 1 of study treatment. Note: patients on = 6 months of chronic or prophylactic anti-coagulation therapy are allowed on study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To assess the efficacy of Etavopivat in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb)<br>• To assess the efficacy of Etavopivat as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate;Secondary Objective: • To measure the effects of Etavopivat on clinical measures and sequelae of hemolysis, • To assess changes in fatigue of adult sickle cell patients taking etavopivat, • To evaluate the effects of Etavopivat on the sequelae of VOC;Primary end point(s): • 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
- Secondary Outcome Measures
Name Time Method Secondary end point(s):1. Change from baseline in Hb at Week 52 during the blinded treatment period;Secondary end point(s):2. Change in SCD-related clinical laboratory measurements from baseline at Week 24 during the blinded treatment period in: o Absolute reticulocyte count, o Indirect bilirubin, and o Lactate dehydrogenase (LDH);Secondary end point(s):3. Change from baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale in adult patients at Week 52 during the blinded treatment period;Secondary end point(s):4. Time to first VOC during the blinded treatment period