Tests etavopivat in children with sickle cell disease

Who can take part

• Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study
• Male or female
• Age 2 to 11 years of age (both inclusive) at the time of randomisation
• Participant has a confirmed diagnosis of SCD: • Documentation of SCD genotype (HbSS, HbSC, HbSβ0 -thalassaemia, HbSβ+ thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing. Molecular genotyping is not required. SCD genotype may be determined from the results of Hb electrophoresis, high-performance liquid chromatography, or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening
• Haemoglobin ≥ 5.5 and ≤ 10.5 g/dL at screening
• At least 2 episodes and a maximum of 15 episodes of documented VOC within the 12 months prior to screening. Documentation must exist in the participant’s medical record prior to screening. Events based solely on participant/parent recall without supporting documentation should not be counted towards eligibility
• Other inclusion criteria apply as outlined in the study protocol

Who cannot take part

• Use of concomitant medications that are strong inducers of CYP3A4/5, 2 weeks prior to randomisation or anticipated need for such concomitant medications during the study
• Known or suspected hypersensitivity to study intervention(s) or related products
• History of overt clinical stroke, intracranial haemorrhage or severe central nervous system vasculopathy on magnetic resonance angiography
• Hepatobiliary disorders or hepatic dysfunction characterised by any of the following at screening: • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN). • Direct bilirubin > 2 × ULN • Liver disease with histopathological evidence or clinical diagnosis of cirrhosis or severe fibrosis
• Participants with iron deficiency (e.g., serum iron less than the lower limit of normal [LLN] or ferritin < 10 µg/L) at screening who are not taking or are unable to take iron supplements during the study. Participants with low serum iron levels due to chronic inflammation or other causes in which supplemental iron therapy is not indicated are allowed to be included in the study
• Other exclusion criteria apply as outlined in the study protocol
• Body weight < 10 kg
• Severe renal dysfunction (estimated glomerular filtration rate <30 mL/min/1.73 m2 or on chronic dialysis)
• Participants with folate (or folic acid or Vitamin B9) or Vitamin B12 deficiency (e.g., folate or Vitamin B12 levels less than the LLN) at screening who are not taking or are unable to take supplements during the study
• Participants who are unable or unwilling to use antimalarial prophylaxis in the form of bed nets and/or effective chemoprophylaxis according to local recommendations if they live in areas of endemic malaria during participation in the study