An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral Etavopivat, a Pyruvate Kinase Activator in Patients With Sickle Cell Disease (HIBISCUS)
An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral Etavopivat, a Pyruvate Kinase Activator in Patients With Sickle Cell Disease (HIBISCUS)
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).
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 is one 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 conclusion of the double-blind treatment period. Following completion of 52 weeks of double-blind treatment, patients may enter a 112-week etavopivat open-label extension period.
Key Inclusion Criteria:
Key Exclusion Criteria:
More than 15 vaso-occlusive crises within the past 12 months
Female who is breastfeeding or pregnant
Hepatic dysfunction characterized by:
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:
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
Atlanta, Georgia 30342, United States
Detroit, Michigan 48201, United States
Chapel Hill, North Carolina 27514, United States
Cincinnati, Ohio 45229, United States
Berlin, 13353, Germany
Freiburg im Breisgau, 79106, Germany
Hamburg, 20246, Germany
Heidelberg, 69120, Germany
Larissa, 41221, Greece
Cutack, 753007, India
Pavia, PV 27100, Italy
Orbassano, 10043, Italy
Palermo, 90127, Italy
Amman, 11844, Lebanon
Adana, 1240, Turkey (Türkiye)
Mersin, 33110, Turkey (Türkiye)
London, SE18 3RA, United Kingdom