Testing Etavopivat against a placebo for sickle cell disease

Exclusion

• −More than 15 VOCs within the past 12 months prior to screeningScreeningThe checks done before joining, to see whether a study fits.Read more → documented in the participant's medical record. Events based solely on participant recall without supporting documentation should not be counted towards eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more →.
• −Use of voxelotor or similar agent within 28 days prior to starting study treatment or anticipated need for this agent during the study.
• −Use of a selectin antagonist (e.g., crizanlizumab, monoclonal antibody or small molecule) within 28 days or 5 half-lives (whichever is longer) prior to starting study 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 transfusion events in the previous 12 months (i.e., an average of 1 transfusion event every 60 days).
• −Participants who have received an RBC transfusion for any reason within 60 days of the screening period or 60 days of the randomisationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more → day are only eligible if HbA (adult haemoglobin) less than 10% by Hb electrophoresis is documented prior to starting 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 need for such agents during the study.
• −Use of erythropoietin or other haematopoietic 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 (e.g., haematopoietic cell transplant, gene modification 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 at the time of consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → and during the study if they live in areas of endemic malaria where 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 chronic dialysis.
• −Travelled distance on standardized 6MWT below 100m at screening.