A Study of Etavopivat in Patients With Thalassemia or Sickle Cell Disease
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04987489 |
|
Recruitment Status :
Recruiting
First Posted : August 3, 2021
Last Update Posted : April 18, 2023
|
Sponsor:
Forma Therapeutics, Inc.
Information provided by (Responsible Party):
Forma Therapeutics, Inc.
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Sickle Cell Disease Thalassemia | Drug: Etavopivat tablets | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2 Open-Label Study to Evaluate Safety and Clinical Activity of Etavopivat in Patients With Thalassemia or Sickle Cell Disease |
| Actual Study Start Date : | December 1, 2021 |
| Estimated Primary Completion Date : | March 30, 2025 |
| Estimated Study Completion Date : | July 31, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Sickle cell disease
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Etavopivat 400 mg daily - SCD with transfusions
Patients with sickle cell disease on chronic red blood cell transfusions
|
Drug: Etavopivat tablets
Etavopivat 400 mg once daily
Other Name: FT-4202 |
|
Experimental: Etavopivat 400 mg daily - Thalassemia with transfusions
Patients with thalassemia on chronic red blood cell transfusions
|
Drug: Etavopivat tablets
Etavopivat 400 mg once daily
Other Name: FT-4202 |
|
Experimental: Etavopivat 400 mg daily - Thalassemia
Patients with thalassemia not on chronic red blood cell transfusions
|
Drug: Etavopivat tablets
Etavopivat 400 mg once daily
Other Name: FT-4202 |
Primary Outcome Measures :
- 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 12 weeks ]Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)
Secondary Outcome Measures :
- 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 [ Time Frame: 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 [ Time Frame: 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 A: Reduction in red blood cell transfusions over 12 weeks [ Time Frame: 12 weeks ]Reduction in red blood cell transfusions over 12 weeks
- Cohort A: Reduction in red blood cell transfusions over 24 weeks [ Time Frame: 24 weeks ]Reduction in red blood cell transfusions over 24 weeks
- Cohort A: Reduction in red blood cell transfusions over 48 weeks [ Time Frame: 48 weeks ]Reduction in red blood cell transfusions over 48 weeks
- Cohort B: Reduction in red blood cell transfusions over 12 weeks [ Time Frame: 12 weeks ]Reduction in red blood cell transfusions over 12 weeks
- Cohort B: Reduction in red blood cell transfusions over 24 weeks [ Time Frame: 24 weeks ]Reduction in red blood cell transfusions over 24 weeks
- Cohort B: Reduction in red blood cell transfusions over 48 weeks [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 48 weeks ]Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline).
- Change from baseline in hemoglobin over 12 weeks [ Time Frame: 12 weeks ]Change from baseline in hemoglobin over 12 weeks
- Change from baseline in hemoglobin over 24 weeks [ Time Frame: 24 weeks ]Change from baseline in hemoglobin over 24 weeks
- Change from baseline in hemoglobin over 48 weeks [ Time Frame: 48 weeks ]Change from baseline in hemoglobin over 48 weeks
- Changes in serum ferritin levels at 12 weeks versus baseline [ Time Frame: 12 weeks ]Changes in serum ferritin levels at 12 weeks versus baseline
- Changes in serum ferritin levels at 24 weeks versus baseline [ Time Frame: 24 weeks ]Changes in serum ferritin levels at 24 weeks versus baseline
- Changes in serum ferritin levels at 48 weeks versus baseline [ Time Frame: 48 weeks ]Changes in serum ferritin levels at 48 weeks versus baseline
- Changes in liver iron concentration at 48 weeks versus baseline [ Time Frame: 48 weeks ]Changes in liver iron concentration at 48 weeks versus baseline
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 12 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04987489
Contacts
| Contact: Leila J Clay, MD | 857-209-2238 | medicalinformation@formatherapeutics.com |
Locations
| United States, California | |
| The Oncology Institute of Hope & Innovation | Recruiting |
| Downey, California, United States, 90241 | |
| Children's Hospital Los Angeles | Recruiting |
| Los Angeles, California, United States, 90027 | |
| University of California, Los Angeles | Recruiting |
| Los Angeles, California, United States, 90095 | |
| University of California - San Francisco | Recruiting |
| Oakland, California, United States, 94609 | |
| Children's Hospital of Orange County | Recruiting |
| Orange, California, United States, 92868 | |
| UCI Health | Recruiting |
| Orange, California, United States, 92868 | |
| United States, District of Columbia | |
| Children's National | Recruiting |
| Washington, District of Columbia, United States, 20010 | |
| United States, New York | |
| Weill Medical College of Cornell University | Recruiting |
| New York, New York, United States, 10065 | |
| United States, North Carolina | |
| Duke Adult Comprehensive Sickle Cell Center | Recruiting |
| Durham, North Carolina, United States, 27710 | |
| East Carolina University | Recruiting |
| Greenville, North Carolina, United States, 27834 | |
| United States, Ohio | |
| Cincinnati Children's Hospital Medical Center | Recruiting |
| Cincinnati, Ohio, United States, 45229 | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Canada | |
| CHU Sainte-Justine | Recruiting |
| Montréal, Canada, H3T 1C5 | |
| The Hospital for Sick Children | Recruiting |
| Toronto, Canada | |
| Lebanon | |
| Nini Hospital | Recruiting |
| Tripoli, Lebanon | |
Sponsors and Collaborators
Forma Therapeutics, Inc.
Investigators
| Study Director: | Leila J Clay, MD | Forma Therapeutics, Inc. |
Additional Information:
| Responsible Party: | Forma Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT04987489 |
| Other Study ID Numbers: |
4202-HEM-201 |
| First Posted: | August 3, 2021 Key Record Dates |
| Last Update Posted: | April 18, 2023 |
| Last Verified: | April 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Forma Therapeutics, Inc.:
|
SCD sickle cell disease sickle cell anemia sickle cell anemia hemolytic hemoglobin vaso-occlusive crisis VOC vaso-occlusive events sickle cell crisis pain crisis pain episode congenital anemia hemolytic anemia |
hematologic disease hemoglobinopathy hemoglobinopathies genetic disease inborn disease sickle cell trait pyruvate kinase PKR thalassemia beta-thalassemia alpha-thalassemia transfusions hemoglobin H transfusion transfusion-dependent |
Additional relevant MeSH terms:
|
Anemia, Sickle Cell Thalassemia Anemia, Hemolytic, Congenital Anemia, Hemolytic |
Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |