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

A Phase 2 Open-Label Study to Evaluate Safety and Clinical Activity of Etavopivat in Patients With Thalassemia or Sickle Cell Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Thalassemia
• Intervention / Treatment: Drug: Etavopivat tablets

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Canada
  • Montréal, Canada, H3T 1C5
    • Recruiting
    • CHU Sainte-Justine
  • Toronto, Canada
    • Recruiting
    • The Hospital for Sick Children
• Lebanon
  • Hazmiyeh, Lebanon, 213
    • Recruiting
    • Chronic Care Center
  • Tripoli, Lebanon
    • Recruiting
    • Nini Hospital
• United States
  • California
    • Downey, California, United States, 90241
      • Recruiting
      • The Oncology Institute of Hope & Innovation
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital Los Angeles
    • Oakland, California, United States, 94609
      • Recruiting
      • University of California - San Francisco
    • Orange, California, United States, 92868
      • Recruiting
      • Children's Hospital of Orange County
    • Orange, California, United States, 92868
      • Recruiting
      • UCI Health
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Medical College of Cornell University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Adult Comprehensive Sickle Cell Center
    • Greenville, North Carolina, United States, 27834
      • Recruiting
      • East Carolina University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: FT-4202

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	Reduction in red blood cell transfusions over 12 weeks	12 weeks
Cohort A: Reduction in red blood cell transfusions over 24 weeks	Reduction in red blood cell transfusions over 24 weeks	24 weeks
Cohort A: Reduction in red blood cell transfusions over 48 weeks	Reduction in red blood cell transfusions over 48 weeks	48 weeks
Cohort B: Reduction in red blood cell transfusions over 12 weeks	Reduction in red blood cell transfusions over 12 weeks	12 weeks
Cohort B: Reduction in red blood cell transfusions over 24 weeks	Reduction in red blood cell transfusions over 24 weeks	24 weeks
Cohort B: Reduction in red blood cell transfusions over 48 weeks	Reduction in red blood cell transfusions over 48 weeks	48 weeks
Cohort C: Hemoglobin response rate at Week 24 (increase of ≥ 1.0 g/dL from baseline).	Hemoglobin response rate at Week 24 (increase of ≥ 1.0 g/dL from baseline).	24 weeks
Cohort C: Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline).	Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline).	48 weeks
Change from baseline in hemoglobin over 12 weeks	Change from baseline in hemoglobin over 12 weeks	12 weeks
Change from baseline in hemoglobin over 24 weeks	Change from baseline in hemoglobin over 24 weeks	24 weeks
Change from baseline in hemoglobin over 48 weeks	Change from baseline in hemoglobin over 48 weeks	48 weeks
Changes in serum ferritin levels at 12 weeks versus baseline	Changes in serum ferritin levels at 12 weeks versus baseline	12 weeks
Changes in serum ferritin levels at 24 weeks versus baseline	Changes in serum ferritin levels at 24 weeks versus baseline	24 weeks
Changes in serum ferritin levels at 48 weeks versus baseline	Changes in serum ferritin levels at 48 weeks versus baseline	48 weeks
Changes in liver iron concentration at 48 weeks versus baseline	Changes in liver iron concentration at 48 weeks versus baseline	48 weeks

Collaborators and Investigators

• Sponsor: Forma Therapeutics, Inc.
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Publications and helpful links

Helpful Links

• https://gladiolusstudy.com

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): November 3, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: hemoglobin; vaso-occlusive crisis; anemia; transfusions; sickle cell disease; transfusion; SCD; sickle cell anemia; VOC; sickle cell; pain crisis; pyruvate kinase; thalassemia; hematologic disease; hemolytic; hemoglobinopathy; beta-thalassemia; vaso-occlusive events; sickle cell crisis; pain episode; congenital anemia; hemolytic anemia; hemoglobinopathies; genetic disease; inborn disease; sickle cell trait; PKR; alpha-thalassemia; hemoglobin H; transfusion-dependent; non-transfusion dependent; hemoglobin E
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Thalassemia
• Other Study ID Numbers: 4202-HEM-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No