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Trial record 1 of 1 for:    NCT04624659
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A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)

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ClinicalTrials.gov Identifier: NCT04624659
Recruitment Status : Recruiting
First Posted : November 12, 2020
Last Update Posted : July 15, 2022
Sponsor:
Information provided by (Responsible Party):
Forma Therapeutics, Inc.

Study Description
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Brief Summary:
This clinical trial is a Phase 2/3 study that will evaluate the efficacy and safety of etavopivat and test how well etavopivat works compared to placebo to improve the amount of hemoglobin in the blood and to reduce the number of vaso-occlusive crises (times when the blood vessels become blocked and cause pain).

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Etavopivat Tablets Drug: Placebo Tablets Phase 2 Phase 3

Detailed Description:
Etavopivat is designed to activate PKR and thereby modulate RBC metabolism by impacting two critical pathways in RBCs. The etavopivat clinical development program will investigate whether decreasing 2,3-DPG may help oxygen bind to hemoglobin (i.e. increasing oxygen affinity), and thereby increase ATP and impact RBC function. This study is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study of patients age 12 to 65 years (inclusive), with sickle cell disease. There are two planned interim analyses in this study design. Initially, patients will be randomized at 1:1:1 to one of two dose levels of etavopivat or placebo. At the first interim analysis, one of the two etavopivat dose levels will be selected for the Phase 3 portion of the study, in which patients will be randomized at 1:1 to the selected etavopivat dose or placebo. Efficacy on hemoglobin will be evaluated at the second interim analysis, and then will be tested along with evaluation of efficacy on vaso-occlusive crises at the final analysis. Following completion of 52 weeks of double-blind treatment, patients may enter a 52-week etavopivat open-label extension period.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 344 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral Etavopivat, a Pyruvate Kinase Activator in Patients With Sickle Cell Disease (HIBISCUS)
Actual Study Start Date : March 26, 2021
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Double blind etavopivat Low Dose
Double blind etavopivat Low Dose
 Drug: Etavopivat Tablets
200 mg once daily
Experimental: Double blind etavopivat High Dose
Double blind etavopivat High Dose
 Drug: Etavopivat Tablets
400 mg once daily
Experimental: Double blind placebo
Double blind placebo
 Drug: Placebo Tablets
Placebo once daily
Experimental: Open label etavopivat
Open label etavopivat
 Drug: Etavopivat Tablets
Selected dose once daily


Outcome Measures
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Primary Outcome Measures :
  1. Hemoglobin response rate [ Time Frame: 24 Weeks ]
    Hemoglobin response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period

  2. Annualized vaso-occlusive crisis [ Time Frame: 52 Weeks ]
    Annualized vaso-occlusive crisis rate during the 52-week blinded treatment period based on adjudicated vaso-occlusive crisis review


Secondary Outcome Measures :
  1. Hemoglobin [ Time Frame: 24 Weeks ]
    Change from baseline in hemoglobin at Week 24 during the blinded treatment period

  2. Hemoglobin [ Time Frame: 52 Weeks ]
    Change from baseline in hemoglobin at Week 52 during the blinded treatment period

  3. Absolute reticulocyte count [ Time Frame: 24 Weeks ]
    Change in absolute reticulocyte count from baseline at Week 24 during the blinded treatment period

  4. Unconjugated bilirubin [ Time Frame: 24 Weeks ]
    Change in unconjugated bilirubin from baseline at Week 24 during the blinded treatment period

  5. Lactate dehydrogenase [ Time Frame: 24 Weeks ]
    Change in lactate dehydrogenase from baseline at Week 24 during the blinded treatment period

  6. Vaso-occlusive crisis [ Time Frame: 52 Weeks ]
    Time to first vaso-occlusive crisis during the blinded treatment period

  7. Patient-Reported Outcome Measurement Information System (PROMIS) [ Time Frame: 24 Weeks ]
    Change in PROMIS Fatigue Scale from baseline in adult patients at Week 24 during the blinded treatment period

  8. Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale [ Time Frame: 52 Weeks ]
    Change in PROMIS Fatigue Scale from baseline in adult patients at Week 52 during the blinded treatment period


Eligibility Criteria
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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Provision of consent
  • Patient has a confirmed diagnosis of sickle cell disease
  • At least 2 episodes of vaso-occlusive crises in the past 12 months
  • Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL (≥ 55 and ≤ 105 g/L) during screening
  • Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 days prior to start of study treatment
  • Patients on crizanlizumab or L-glutamine treatment at the time of consent must be on a stable dose for ≥ 12 months and must be ≥ 80% compliant with the planned regimen at the time of consent and meet the VOC eligibility criteria
  • Female patients of childbearing potential must use highly effective methods of contraception, male patients are willing to use barrier methods of contraception

Key Exclusion Criteria:

  • More than 10 vaso-occlusive crises within the past 12 months
  • Female who is breastfeeding or pregnant

  • Hepatic dysfunction characterized by:

    • Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN)
    • Direct bilirubin > 3.0 × ULN
  • Known HIV positivity
  • Active hepatitis B or hepatitis C infection
  • Severe renal dysfunction or on chronic dialysis

  • 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
  • History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage
  • History of deep venous thrombosis requiring systemic anti-coagulation therapy for ≥ 6 weeks, occurring within 6 months prior to Day 1 of study treatment.

Prior/Concomitant Therapy

  • Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)
  • Receiving or use of concomitant medications that are strong inducers of CYP3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study
  • Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study
  • Use of an experimental selectin antagonist (eg, monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study
  • Use of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study
  • Receipt of prior cellular-based therapy (eg, hematopoietic cell transplant, gene modification therapy)
Contacts and Locations
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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): NCT04624659


Contacts
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Contact: Forma Therapeutics, Inc. 617-679-1970 clinicaltrials@formatherapeutics.com

Locations
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Sponsors and Collaborators
Forma Therapeutics, Inc.
Investigators
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Study Director: Vandy Black, MD Forma Therapeutics, Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Forma Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04624659    
Other Study ID Numbers: 4202-HEM-301
First Posted: November 12, 2020    Key Record Dates
Last Update Posted: July 15, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Forma Therapeutics, Inc.:
Sickle Cell Disease
Sickle Cell
Anemia
Sickle Cell Anemia
Hemolytic
Hemoglobin
Vaso-occlusive Crisis
Sickle Cell Crisis
 Congenital Anemia
Hemolytic Anemia
Hematologic Disease
Hemoglobinopathies
Genetic Disease
Inborn Disease
Sickle Cell Trait
Pyruvate Kinase
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
 Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn