An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral Etavopivat, a Pyruvate Kinase Activator in Patients With Sickle Cell Disease (HIBISCUS)

About the study

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).

Study point of contact

Vandy Black, MD
857-209-2236
[email protected]

Age

12 Years - 65 Years

Phase

Phase 2/Phase 3

Study type

Interventional

Gender

All

Interventions

Drug

participation requirements

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

participation restrictions

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)

Last updated 2022-10-11