A Research Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease

Inclusion Criteria:

• Male or female.

• Age 12 years or above at the time of signing the informed consent.

• Confirmed diagnosis of sickle cell disease: Documentation of sickle cell disease (SCD) genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants)based on prior history of laboratory testing or screening test results from centrallaboratory. Molecular genotyping is not required. SCD genotype may be determinedfrom the results of haemoglobin (Hb) electrophoresis, high-performance liquidchromatography (HPLC) or similar testing. Note that Hb electrophoresis is performedby the central laboratory at screening.

• Have 1-15 episodes of documented vaso occlusive crises (VOC) within the 12 monthsprior to screening. Documentation must exist in the participant's medical recordprior to randomisation. Events based solely on participant recall without supportingdocumentation should not be counted towards eligibility.

• Hb greater than or equal to (≥) 5.0 and less than or equal to (≤) 10.0 g/dL (greaterthan or equal to (≥) 50 and less than or equal to (≤) 100 g/L) at screening.

Exclusion Criteria:

• More than 15 VOCs within the past 12 months prior to screening documented in theparticipant's medical record. Events based solely on participant recall withoutsupporting documentation should not be counted towards eligibility.

• Use of voxelotor or similar agent within 28 days prior to starting study treatmentor anticipated need for this agent during the study.

• Use of a selectin antagonist (e.g., crizanlizumab, monoclonal antibody or smallmolecule) within 28 days or 5 half-lives (whichever is longer) prior to startingstudy treatment or anticipated need for such agents during the study.

• Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic,prophylactic, or preventive transfusion) or greater than or equal to 6 transfusionevents in the previous 12 months (i.e., an average of 1 transfusion event every 60days).

• Participants who have received an RBC transfusion for any reason within 60 days ofthe screening period or 60 days of the randomisation day are only eligible if HbA (adult haemoglobin) less than 10% by Hb electrophoresis is documented prior tostarting study treatment.

• Receiving or use of concomitant medications that are strong inducers of CYP3A4 (cytochrome p450 3a4) within 2 weeks of starting study treatment or anticipated needfor such agents during the study.

• Use of erythropoietin or other haematopoietic growth factor treatment within 28 daysof starting study treatment or anticipated need for such agents during the study.

• Receipt of prior cellular-based therapy (e.g., haematopoietic cell transplant, genemodification therapy).

• Hepatic dysfunction characterized by:

• Alanine aminotransferase (ALT) greater than 4.0 × upper limit of normal (ULN)or

• Direct bilirubin greater than 3.0 × ULN.

• Participants who are not taking or are unable to take antimalarial prophylaxis atthe time of consent and during the study if they live in areas of endemic malariawhere prophylaxis is recommended.

• Severe renal dysfunction (estimated glomerular filtration rate [eGFR] at screening,calculated by the central laboratory greater than 30 mL/min/1.73 m^ 2) or on chronicdialysis.

• Travelled distance on standardized 6MWT below 100m at screening.