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A Study of FT-4202 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 : August 10, 2021
Sponsor:
Information provided by (Responsible Party):
Forma Therapeutics, Inc.

Brief Summary:
This clinical trial is a Phase 2/3 study that will evaluate the efficacy and safety of FT-4202 and test how well FT-4202 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: FT-4202 Tablets Drug: Placebo Tablets Phase 2 Phase 3

Detailed Description:
FT-4202 is designed to activate PKR and thereby modulate RBC metabolism by impacting two critical pathways in RBCs. The FT-4202 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 FT-4202 or placebo. At the first interim analysis, one of the two FT-4202 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 FT-4202 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 FT-4202 open-label extension period.

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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 FT-4202, 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


Arm Intervention/treatment
Experimental: Double blind FT-4202 Low Dose Drug: FT-4202 Tablets
200 mg once daily

Experimental: Double blind FT-4202 High Dose Drug: FT-4202 Tablets
400 mg once daily

Experimental: Double Blind Placebo Drug: Placebo Tablets
Placebo once daily

Experimental: Open label FT-4202 Drug: FT-4202 Tablets
Selected dose once daily




Primary Outcome Measures :
  1. Hemoglobin response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period [ Time Frame: 24 Weeks ]
  2. Annualized vaso-occlusive crisis rate during the 52-week blinded treatment period based on adjudicated vaso-occlusive crisis review [ Time Frame: 52 Weeks ]

Secondary Outcome Measures :
  1. Change from baseline in hemoglobin at Week 24 during the blinded treatment period [ Time Frame: 24 Weeks ]
  2. Change in Sickle Cell Disease related clinical laboratory measurements from baseline at Week 24 during the blinded treatment period [ Time Frame: 24 Weeks ]
    • % reticulocytes,
    • Unconjugated bilirubin
    • Lactate dehydrogenase (LDH)

  3. Time to first vaso-occlusive during the blinded treatment period [ Time Frame: 52 Weeks ]
  4. Change from baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale at Week 24 during the blinded treatment period [ Time Frame: 24 Weeks ]
    Adult patients (ages 18 to 65) will complete the PROMIS® Item Bank v.1.0 - Fatigue - Short Form 7a. Adolescent patients (ages 12 to 17) will complete the PROMIS® Item Bank v2.0 - Fatigue - Short Form 10a. Responses are graded on a score of 1 to 5 with a higher score indicating a worse outcome.



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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

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 g/dL (≥ 55 and ≤ 100 g/L) during screening
  • Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 days prior to start of study treatment
  • 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:

Medical Conditions

  • More than 10 vaso-occlusive crises within the past 12 months
  • 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
  • Known HIV positive
  • 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

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 or moderate/strong inhibitors 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 a selectin antagonist (eg, crizanlizumab or other 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)

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
Show Show 23 study locations
Sponsors and Collaborators
Forma Therapeutics, Inc.
Investigators
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Study Director: Vandy Black, MD Forma Therapeutics, Inc.
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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: August 10, 2021
Last Verified: August 2021

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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