A Study of Etavopivat in Patients With Thalassemia or Sickle Cell Disease

NCT04987489 | Completed Phase 2 FDA Drug

• 1 other identifier: 4202-HEM-201
• Study Type: interventional
• Target: 53
• Locations: 6 countries
• Sites: 32

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.

Conditions

Sickle Cell Disease; Thalassemia

Keywords

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; non-transfusion dependent; hemoglobin E

Outcome Measures

Primary Outcomes (3)

• 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

  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

• 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

  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

• Cohort C: Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)

  Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)

  12 weeks

Secondary Outcomes (17)

• 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

• 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

• Cohort A: Reduction in red blood cell transfusions over 12 weeks

  12 weeks

• Cohort A: Reduction in red blood cell transfusions over 24 weeks

  24 weeks

• Cohort A: Reduction in red blood cell transfusions over 48 weeks

  48 weeks

Study Arms (3)

Etavopivat 400 mg daily - SCD with transfusions

EXPERIMENTAL

Patients with sickle cell disease on chronic red blood cell transfusions

Drug: Etavopivat tablets

Etavopivat 400 mg daily - Thalassemia with transfusions

EXPERIMENTAL

Patients with thalassemia on chronic red blood cell transfusions

Drug: Etavopivat tablets

Etavopivat 400 mg daily - Thalassemia

EXPERIMENTAL

Patients with thalassemia not on chronic red blood cell transfusions

Drug: Etavopivat tablets

Interventions

Etavopivat tablets DRUG

Etavopivat 400 mg once daily

Also known as: FT-4202

Etavopivat 400 mg daily - SCD with transfusions; Etavopivat 400 mg daily - Thalassemia; Etavopivat 400 mg daily - Thalassemia with transfusions

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Forma Therapeutics, Inc.: lead

Study Sites (32)

TOI Clinical Research

Cerritos, California, 90703, United States

Location

[Legal] Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of Californ LA-UCLA

Los Angeles, California, 90095, United States

Location

UCSF Oakland Benioff ChildHosp

Oakland, California, 94609, United States

Location

[Legal] Children's Hospital of Orange County on behalf of CHOC Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCI Health

Orange, California, 92868, United States

Location

Children's National Health Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Children's Hospital of Atlanta

Atlanta, Georgia, 30342, United States

Location

[Legal] Dr. Vince Clinical Research, LLC and Dr. Vince Clinical Research, P.A.

Detroit, Michigan, 48201-2018, United States

Location

Weill Medical College of Cornell University

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

[Legal] Children's Hospital Medical Center dba Cincinnati Children's

Cincinnati, Ohio, 45229, United States

Location

Children's Hosptl Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Master Centre for Canada

Mississauga, Ontario, L4W 4XI, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

University Health Network - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

CHU Sainte-Justine Mother and Child University Hospital

Montreal, Quebec, H3T 1C5, Canada

Location

Cairo University

Cairo, 12613, Egypt

Location

Abu El-Reesh El-Mounira Children University Hospital

Cairo, Egypt, 4241317, Egypt

Location

Galliera Hospital Centro Anemie Congenite

Genova, 16128, Italy

Location

Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

AORN A. Cardarelli

Naples, 80131, Italy

Location

A.O.U. Università Studi della Campania "Luigi Vanvitelli"

Naples, 80138, Italy

Location

Chronic Care Center

Baabda, RGWX 4CG, Lebanon

Location

Hospital Nini

Tripoli, 1434, Lebanon

Location

Sandwell and West Birmingham NHS Trust SCAT/ haematology

Birmingham, B18 7QH, United Kingdom

Location

Barts Health NHS Trust - The Royal London Hospital

London, E1 1FR, United Kingdom

Location

University College Hospital - University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

Kings College London

London, SE5 9RS, United Kingdom

Location

Hammersmith Hospital - London

London, W12 0HS, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Thalassemia; Anemia; Hemolysis; Vaso-Occlusive Crises; Anemia, Hemolytic; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Sickle Cell Trait; beta-Thalassemia; alpha-Thalassemia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: August 3, 2021
• Study Start: March 28, 2022
• Primary Completion: September 3, 2025
• Study Completion: September 24, 2025
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

LE (2); CA (4); IT (4); EG (2); GB (6); US (14)