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

Primary Purpose

Sickle Cell Disease, Thalassemia

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Etavopivat tablets
Sponsored by
Novo Nordisk A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring 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

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Oncology Institute of Hope & InnovationRecruiting
  • Children's Hospital Los AngelesRecruiting
  • University of California, Los AngelesRecruiting
  • University of California - San FranciscoRecruiting
  • Children's Hospital of Orange CountyRecruiting
  • UCI HealthRecruiting
  • Children's NationalRecruiting
  • Weill Medical College of Cornell UniversityRecruiting
  • Duke Adult Comprehensive Sickle Cell CenterRecruiting
  • East Carolina UniversityRecruiting
  • Cincinnati Children's Hospital Medical CenterRecruiting
  • Children's Hospital of PhiladelphiaRecruiting
  • CHU Sainte-JustineRecruiting
  • The Hospital for Sick ChildrenRecruiting
  • Nini HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Etavopivat 400 mg daily - SCD with transfusions

Etavopivat 400 mg daily - Thalassemia with transfusions

Etavopivat 400 mg daily - Thalassemia

Arm Description

Patients with sickle cell disease on chronic red blood cell transfusions

Patients with thalassemia on chronic red blood cell transfusions

Patients with thalassemia not on chronic red blood cell transfusions

Outcomes

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

Full Information

First Posted
July 22, 2021
Last Updated
August 8, 2023
Sponsor
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT04987489
Brief Title
A Study of Etavopivat in Patients With Thalassemia or Sickle Cell Disease
Official Title
A Phase 2 Open-Label Study to Evaluate Safety and Clinical Activity of Etavopivat in Patients With Thalassemia or Sickle Cell Disease
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2021 (Actual)
Primary Completion Date
March 30, 2025 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Etavopivat 400 mg daily - SCD with transfusions
Arm Type
Experimental
Arm Description
Patients with sickle cell disease on chronic red blood cell transfusions
Arm Title
Etavopivat 400 mg daily - Thalassemia with transfusions
Arm Type
Experimental
Arm Description
Patients with thalassemia on chronic red blood cell transfusions
Arm Title
Etavopivat 400 mg daily - Thalassemia
Arm Type
Experimental
Arm Description
Patients with thalassemia not on chronic red blood cell transfusions
Intervention Type
Drug
Intervention Name(s)
Etavopivat tablets
Other Intervention Name(s)
FT-4202
Intervention Description
Etavopivat 400 mg once daily
Primary Outcome Measure Information:
Title
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
Description
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
Title
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
Description
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
Title
Cohort C: Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)
Description
Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
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
Description
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
Title
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
Description
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
Title
Cohort A: Reduction in red blood cell transfusions over 12 weeks
Description
Reduction in red blood cell transfusions over 12 weeks
Time Frame
12 weeks
Title
Cohort A: Reduction in red blood cell transfusions over 24 weeks
Description
Reduction in red blood cell transfusions over 24 weeks
Time Frame
24 weeks
Title
Cohort A: Reduction in red blood cell transfusions over 48 weeks
Description
Reduction in red blood cell transfusions over 48 weeks
Time Frame
48 weeks
Title
Cohort B: Reduction in red blood cell transfusions over 12 weeks
Description
Reduction in red blood cell transfusions over 12 weeks
Time Frame
12 weeks
Title
Cohort B: Reduction in red blood cell transfusions over 24 weeks
Description
Reduction in red blood cell transfusions over 24 weeks
Time Frame
24 weeks
Title
Cohort B: Reduction in red blood cell transfusions over 48 weeks
Description
Reduction in red blood cell transfusions over 48 weeks
Time Frame
48 weeks
Title
Cohort C: Hemoglobin response rate at Week 24 (increase of ≥ 1.0 g/dL from baseline).
Description
Hemoglobin response rate at Week 24 (increase of ≥ 1.0 g/dL from baseline).
Time Frame
24 weeks
Title
Cohort C: Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline).
Description
Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline).
Time Frame
48 weeks
Title
Change from baseline in hemoglobin over 12 weeks
Description
Change from baseline in hemoglobin over 12 weeks
Time Frame
12 weeks
Title
Change from baseline in hemoglobin over 24 weeks
Description
Change from baseline in hemoglobin over 24 weeks
Time Frame
24 weeks
Title
Change from baseline in hemoglobin over 48 weeks
Description
Change from baseline in hemoglobin over 48 weeks
Time Frame
48 weeks
Title
Changes in serum ferritin levels at 12 weeks versus baseline
Description
Changes in serum ferritin levels at 12 weeks versus baseline
Time Frame
12 weeks
Title
Changes in serum ferritin levels at 24 weeks versus baseline
Description
Changes in serum ferritin levels at 24 weeks versus baseline
Time Frame
24 weeks
Title
Changes in serum ferritin levels at 48 weeks versus baseline
Description
Changes in serum ferritin levels at 48 weeks versus baseline
Time Frame
48 weeks
Title
Changes in liver iron concentration at 48 weeks versus baseline
Description
Changes in liver iron concentration at 48 weeks versus baseline
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leila J Clay, MD
Phone
857-209-2238
Email
medicalinformation@formatherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leila J Clay, MD
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
The Oncology Institute of Hope & Innovation
City
Downey
State/Province
California
ZIP/Postal Code
90241
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California - San Francisco
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
UCI Health
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's National
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Name
Duke Adult Comprehensive Sickle Cell Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Name
East Carolina University
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Individual Site Status
Recruiting
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
CHU Sainte-Justine
City
Montréal
ZIP/Postal Code
H3T 1C5
Country
Canada
Individual Site Status
Recruiting
Facility Name
The Hospital for Sick Children
City
Toronto
Country
Canada
Individual Site Status
Recruiting
Facility Name
Nini Hospital
City
Tripoli
Country
Lebanon
Individual Site Status
Recruiting

12. IPD Sharing Statement

Links:
URL
https://gladiolusstudy.com
Description
https://gladiolusstudy.com

Learn more about this trial

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

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