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

Launched by NOVO NORDISK A/S · Sep 23, 2024

Keywords

ClinConnect Summary

This clinical trial is testing a new medication called etavopivat to see how well it helps people with sickle cell disease. Specifically, the study aims to find out if etavopivat can reduce painful episodes known as vaso-occlusive crises (VOCs), lower damage to organs, improve exercise ability, and decrease feelings of tiredness. Participants in the study will either receive etavopivat or a placebo (a treatment with no active medication), and which one they get will be decided by chance. The study will last for about two years.

To join the trial, participants need to be at least 12 years old and have a confirmed diagnosis of sickle cell disease, along with a history of experiencing 1 to 15 VOCs in the past year. They should be healthy enough to meet other specific criteria, such as having certain blood levels. Throughout the study, participants will have regular check-ups and assessments to monitor their health and response to the treatment. It's important to note that some individuals may not be eligible if they have had too many VOCs recently or have received other treatments that might interfere with the study.

Gender

ALL

Eligibility criteria

• 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 central laboratory. Molecular genotyping is not required. SCD genotype may be determined from the results of haemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC) or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening.
• • Have 1-15 episodes of documented vaso occlusive crises (VOC) within the 12 months prior to screening. Documentation must exist in the participant's medical record prior to randomisation. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.
• • Hb greater than or equal to (≥) 5.0 and less than or equal to (≤) 10.0 g/dL (greater than 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 the participant's medical record. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.
• • 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 randomisation 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 consent 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.