A Study of FT-4202 in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)
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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
Sickle Cell Disease
Drug: FT-4202 TabletsDrug: Placebo Tablets
Phase 2Phase 3
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.
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 ]
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 :
Change from baseline in hemoglobin at Week 24 during the blinded treatment period [ Time Frame: 24 Weeks ]
Change in Sickle Cell Disease related clinical laboratory measurements from baseline at Week 24 during the blinded treatment period [ Time Frame: 24 Weeks ]
Lactate dehydrogenase (LDH)
Time to first vaso-occlusive during the blinded treatment period [ Time Frame: 52 Weeks ]
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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Layout table for eligibility information
Ages Eligible for Study:
12 Years to 65 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
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:
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
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