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

Etavopivat (FT-4202) is a potent, selective, orally bioavailable, small-molecule activator of erythrocyte pyruvate kinase (PKR) being developed by Forma Therapeutics, Inc. and is intended for use as a treatment for participants with sickle cell disease (SCD) and other inherited hemoglobinopathies. The clinical hypothesis is that PKR activation will reduce sickle hemoglobin (HbS) polymerization and improve red blood cell (RBC) membrane function, thereby reducing RBC sickling and RBC hemolysis that leads to vascular obstruction and anemia, two hallmarks of SCD pathology. The aim of this study is to determine the effects of etavopivat on cerebral and muscle hemodynamics

Inclusion Criteria:Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta0 thalassemia (HbS/β0 thal)Hemoglobin (Hb): Hb ≤ 9.0 g/dL at baselineConcomitant 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 toxicityExclusion 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 sequestrationDactylitisRequires chronic transfusion therapyAbnormal TCD in the last 12 monthsRBC transfusion within 60 days of screeningSevere renal dysfunction at the Screening Visit or on chronic dialysisHepatic dysfunctionClinically relevant cardiac or pulmonary disease- e.g., congenital heart defect, uncompensated heart failure, or any unstable cardiac condition, arrhythmic heart condition, pulmonary fibrosis, pulmonary hypertensionMajor surgery involving the stomach or small intestineChemotherapy or radiation within the past 2 yearsHistory of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhageClinically significant bacterial, fungal, parasitic, or viral infection currently receiving or that will require therapyFemale who is breast feeding or pregnant