A Study of Etavopivat in Patients With Thalassemia or Sickle Cell Disease
- Conditions
- Sickle Cell DiseaseThalassemia
- Interventions
- Registration Number
- NCT04987489
- Lead Sponsor
- Forma Therapeutics, Inc.
- Brief Summary
This clinical trial is a Phase 2 study that will evaluate the safety and clinical activity of etavopivat in patients with thalassemia or sickle cell disease and test how well etavopivat works to lower the number of red blood cell transfusions required and increase hemoglobin.
- Detailed Description
Etavopivat is a potent, selective, orally bioavailable, small-molecule activator of pyruvate kinase red blood cell (PKR) being developed by Forma Therapeutics, Inc and is intended for use as a treatment for patients with sickle cell disease (SCD) or other inherited hemoglobinopathies or refractory anemias. This study is a multicenter, Phase 2, open-label, multiple-cohort study examining the safety and efficacy of etavopivat for the treatment of patients, age 12 to 65 years, with SCD or thalassemia. Three treatment cohorts based on the patients hemoglobinopathy (SCD or thalassemia) and transfusion requirements will be evaluated.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Provision of consent
- Female patients of childbearing potential must use acceptable methods of contraception, male patients are willing to use barrier methods of contraception
Cohort A (Sickle Cell Disease Transfusion Cohort)
- Confirmed diagnosis of sickle cell disease
- Chronically red blood cell transfused (sample or exchange [manual or via electrophoresis]) for primary stroke prevention or due to previous stroke. Chronic red blood cell transfusion is defined as: ≥ 6 red blood cell units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for > 35 days during that period
- At least 24 months of chronic monthly red blood cell transfusions for secondary stroke prevention/treatment of primary stroke (initial completed overt clinical stroke with documented infarction on brain computed tomography [CT] or magnetic resonance imaging [MRI])
- Prior to screening OR at least 12 months of chronic RBC transfusions for primary stroke prevention (abnormal TCD) prior to screening
- Documented adequate monthly transfusions with average HbS ≤ 45% (the upper limit of the established academic community standard) for the previous 12 weeks of red blood cell transfusions before the first dose of study treatment
Cohort B (Thalassemia Transfusion Cohort)
- Documented diagnosis of β-thalassemia, Hemoglobin E/ β-thalassemia or Hemoglobin H (α-thalassemia), or other thalassemia variant
- Chronically transfused, defined as: ≥ 6 red blood cell units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for > 35 days during that period
Cohort C (Thalassemia Non-transfused Cohort)
- Documented diagnosis of β-thalassemia, Hemoglobin E/ β-thalassemia or Hemoglobin H (α-thalassemia), or other thalassemia variant
- Hemoglobin ≤ 10 g/dL
-
Female who is breast feeding or pregnant
-
Hepatic dysfunction characterized by:
- Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN)
- Direct bilirubin > 3.0 × ULN
- History of cirrhosis
-
Known human immunodeficiency virus (HIV) positivity
-
Active hepatitis B or hepatitis C infection
-
Severe renal dysfunction or on chronic dialysis
-
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, non- melanoma skin cancer, cancer of the cervix in-situ, ductal carcinoma in situ [Stage 1], Grade 1 endometrial cancer)
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Etavopivat 400 mg daily - Thalassemia Etavopivat tablets Patients with thalassemia not on chronic red blood cell transfusions Etavopivat 400 mg daily - SCD with transfusions Etavopivat tablets Patients with sickle cell disease on chronic red blood cell transfusions Etavopivat 400 mg daily - Thalassemia with transfusions Etavopivat tablets Patients with thalassemia on chronic red blood cell transfusions
- Primary Outcome Measures
Name Time Method Cohorts A: Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history 12 weeks Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history
Cohorts B: Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history 12 weeks Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history
Cohort C: Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline) 12 weeks Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)
- Secondary Outcome Measures
Name Time Method Cohort A: Reduction in red blood cell transfusions over 12 weeks 12 weeks Reduction in red blood cell transfusions over 12 weeks
Cohort A: Reduction in red blood cell transfusions over 48 weeks 48 weeks Reduction in red blood cell transfusions over 48 weeks
Change from baseline in hemoglobin over 48 weeks 48 weeks Change from baseline in hemoglobin over 48 weeks
Cohort A: Reduction in red blood cell transfusions over 24 weeks 24 weeks Reduction in red blood cell transfusions over 24 weeks
Changes in serum ferritin levels at 48 weeks versus baseline 48 weeks Changes in serum ferritin levels at 48 weeks versus baseline
Cohort A: Proportion of patients with ≥ 33% reduction in red blood cell transfusion over a continuous 12-week treatment period versus baseline red blood cell transfusion history 12 weeks Proportion of patients with ≥ 33% reduction in red blood cell transfusion over a continuous 12-week treatment period versus baseline red blood cell transfusion history
Cohort B: Proportion of patients with ≥ 33% reduction in red blood cell transfusion over a continuous 12-week treatment period versus baseline red blood cell transfusion history 12 weeks Proportion of patients with ≥ 33% reduction in red blood cell transfusion over a continuous 12-week treatment period versus baseline red blood cell transfusion history
Cohort B: Reduction in red blood cell transfusions over 12 weeks 12 weeks Reduction in red blood cell transfusions over 12 weeks
Cohort B: Reduction in red blood cell transfusions over 24 weeks 24 weeks Reduction in red blood cell transfusions over 24 weeks
Cohort B: Reduction in red blood cell transfusions over 48 weeks 48 weeks Reduction in red blood cell transfusions over 48 weeks
Cohort C: Hemoglobin response rate at Week 24 (increase of ≥ 1.0 g/dL from baseline). 24 weeks Hemoglobin response rate at Week 24 (increase of ≥ 1.0 g/dL from baseline).
Cohort C: Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline). 48 weeks Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline).
Change from baseline in hemoglobin over 12 weeks 12 weeks Change from baseline in hemoglobin over 12 weeks
Change from baseline in hemoglobin over 24 weeks 24 weeks Change from baseline in hemoglobin over 24 weeks
Changes in liver iron concentration at 48 weeks versus baseline 48 weeks Changes in liver iron concentration at 48 weeks versus baseline
Changes in serum ferritin levels at 24 weeks versus baseline 24 weeks Changes in serum ferritin levels at 24 weeks versus baseline
Changes in serum ferritin levels at 12 weeks versus baseline 12 weeks Changes in serum ferritin levels at 12 weeks versus baseline
Trial Locations
- Locations (16)
[Legal] Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
UCSF Oakland Benioff ChildHosp
🇺🇸Oakland, California, United States
[Legal] Children's Hospital of Orange County on behalf of CHOC Children's Hospital of Orange County
🇺🇸Orange, California, United States
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
[Legal] Children's Hospital Medical Center dba Cincinnati Children's
🇺🇸Cincinnati, Ohio, United States
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
University Health Network - Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
CHU Sainte-Justine Mother and Child University Hospital
🇨🇦Montreal, Quebec, Canada
Abu El-Reesh El-Mounira Children University Hospital
🇪🇬Cairo, Egypt, Egypt
Cairo University
🇪🇬Cairo, Egypt
Chronic Care Center
🇱🇧Baabda, Lebanon
Hospital Nini
🇱🇧Tripoli, Lebanon
Barts Health NHS Trust - The Royal London Hospital
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust - Hammersmith Hospital
🇬🇧London, United Kingdom
Manchester University NHS Foundation Trust
🇬🇧Manchester, United Kingdom