A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)

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 ≤ 10.5 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

Exclusion Criteria

• More than 15 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)