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

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04987489
• Other study ID #: 4202-HEM-201
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: April 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 1, 2025
• Est. primary completion date: November 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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 ß-thalassemia, Hemoglobin E/ ß-thalassemia or Hemoglobin H (a-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 ß-thalassemia, Hemoglobin E/ ß-thalassemia or Hemoglobin H (a-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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease
• Thalassemia

Intervention

Drug:
• Etavopivat tablets
Etavopivat 400 mg once daily

Locations

Country	Name	City	State
Canada	CHU Sainte-Justine	Montréal
Canada	The Hospital for Sick Children	Toronto
Lebanon	Chronic Care Center	Hazmiyeh
Lebanon	Nini Hospital	Tripoli
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The Oncology Institute of Hope & Innovation	Downey	California
United States	Duke Adult Comprehensive Sickle Cell Center	Durham	North Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Weill Medical College of Cornell University	New York	New York
United States	University of California - San Francisco	Oakland	California
United States	Children's Hospital of Orange County	Orange	California
United States	UCI Health	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's National	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Forma Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Lebanon, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Cohort A: Reduction in red blood cell transfusions over 12 weeks	Reduction in red blood cell transfusions over 12 weeks	12 weeks
Secondary	Cohort A: Reduction in red blood cell transfusions over 24 weeks	Reduction in red blood cell transfusions over 24 weeks	24 weeks
Secondary	Cohort A: Reduction in red blood cell transfusions over 48 weeks	Reduction in red blood cell transfusions over 48 weeks	48 weeks
Secondary	Cohort B: Reduction in red blood cell transfusions over 12 weeks	Reduction in red blood cell transfusions over 12 weeks	12 weeks
Secondary	Cohort B: Reduction in red blood cell transfusions over 24 weeks	Reduction in red blood cell transfusions over 24 weeks	24 weeks
Secondary	Cohort B: Reduction in red blood cell transfusions over 48 weeks	Reduction in red blood cell transfusions over 48 weeks	48 weeks
Secondary	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
Secondary	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
Secondary	Change from baseline in hemoglobin over 12 weeks	Change from baseline in hemoglobin over 12 weeks	12 weeks
Secondary	Change from baseline in hemoglobin over 24 weeks	Change from baseline in hemoglobin over 24 weeks	24 weeks
Secondary	Change from baseline in hemoglobin over 48 weeks	Change from baseline in hemoglobin over 48 weeks	48 weeks
Secondary	Changes in serum ferritin levels at 12 weeks versus baseline	Changes in serum ferritin levels at 12 weeks versus baseline	12 weeks
Secondary	Changes in serum ferritin levels at 24 weeks versus baseline	Changes in serum ferritin levels at 24 weeks versus baseline	24 weeks
Secondary	Changes in serum ferritin levels at 48 weeks versus baseline	Changes in serum ferritin levels at 48 weeks versus baseline	48 weeks
Secondary	Changes in liver iron concentration at 48 weeks versus baseline	Changes in liver iron concentration at 48 weeks versus baseline	48 weeks

External Links

•   https://gladiolusstudy.com