Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease

This study is a pilot, open-label, single-arm study to evaluate the effect of etavopivat on cerebral hemodynamics, as measured by frequency domain near-infrared spectroscopy/diffuse correlation spectroscopy (FDNIRS/DCS) in participants 12 to 21 years of age with sickle cell disease (SCD). Cerebral blood flow (CBF), oxygen ejection fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) will be assessed FDNIRS/DCS in participants prior to, periodically throughout, and after 24 weeks of treatment with etavopivat. Approximately 12 participants will be enrolled.

The duration of study treatment will be 24 weeks. The study duration for individual participants may last up to 36 to 38 weeks and includes the Screening Period (up to 4 weeks before study treatment), the 24-week treatment period, a Safety Follow-up Visit at 4 weeks (+ 7 days) after the last dose of study drug, and an End of Study (EOS) visit approximately 8 weeks (± 7 days) after the last dose of study drug. A participant is considered to have completed the study if he or she has completed all phases of the study including the last visit or the last scheduled procedure shown in the Schedule of Events.

Inclusion criteria

• Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta0 thalassemia (HbS/β0 thal)
• Hemoglobin (Hb): Hb ≤ 9.0 g/dL at baseline
• Concomitant hydroxyurea (HU) therapy is allowed if the dose has been stable for at least 3 months with no anticipated need for dose adjustments during the study and no sign of hematological toxicity

Exclusion criteria

• Any one of the following requiring a medical facility visit within 14 days prior to signing the informed consent form:

• Vaso-occlusive crisis (VOC)
• Acute chest syndrome (ACS)
• Splenic sequestration
• Dactylitis
• Requires chronic transfusion therapy
• Abnormal TCD in the last 12 months
• RBC transfusion within 60 days of screening
• Severe renal dysfunction at the Screening Visit or on chronic dialysis
• Hepatic dysfunction
• Clinically relevant cardiac or pulmonary disease- e.g., congenital heart defect, uncompensated heart failure, or any unstable cardiac condition, arrhythmic heart condition, pulmonary fibrosis, pulmonary hypertension
• Major surgery involving the stomach or small intestine
• Chemotherapy or radiation within the past 2 years
• History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage
• Clinically significant bacterial, fungal, parasitic, or viral infection currently receiving or that will require therapy
• Female who is breast feeding or pregnant