A Study of FT-4202 in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)

Purpose

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

  • Sickle Cell Disease

Eligibility

Eligible Ages
Between 12 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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)

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Elizabeth Pottier
617-638-7480
elizabeth.pottier@bmc.org

More Details

Status
Recruiting
Sponsor
Forma Therapeutics, Inc.

Study Contact

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

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.