NCT06612268RecruitingPhase 3
A Global Phase 3, Randomised, Double-blind and Placebo-controlled Study Evaluating the Efficacy and Safety of Etavopivat in Adolescents and Adults With Sickle Cell Disease
Novo Nordisk A/S317 sites in 3 countries510 target enrollmentStarted: February 17, 2025Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Novo Nordisk A/S
- Enrollment
- 510
- Locations
- 317
- Primary Endpoint
- Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact
Study Overview
Brief Summary
This study is conducted to confirm whether etavopivat works well at reducing the number of Vaso-occlusive crisis VOCs (sickle cell pain crises) caused by obstructions in blood vessels in adults and adolescents living with sickle cell disease. The study will also evaluate how well etavopivat can reduce the damage to different organs, improve your exercise tolerance and reduce fatigue in people with sickle cell disease.The participants will either get etavopivat or placebo. Which treatment the participants will get is decided by chance. Etavopivat is a new medicine and is currently being tested in other studies in addition to this one. The study will last for about 2 years.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 2-15 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 grams per litre [g/L]) at screening.
Exclusion Criteria
- •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 within the previous 12 months prior to screening (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 or moderate 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.
Arms & Interventions
Etavopivat
Experimental
Participants will be randomised to receive oral dose of Etavopivat.
Intervention: Etavopivat (Drug)
Placebo
Placebo Comparator
Participants will be randomised to receive oral dose of placebo.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact
Time Frame: Baseline (week 0) to week 52
Measured as Count of events.
Secondary Outcomes
- Time to onset of first adjudicated Vaso-occlusive crisis (VOC)(Baseline (week 0) to week 52)
- Change in distance travelled during the 6-minute walking test (6MWT)(Baseline (week 0) to week 52)
- Change in standardised T-score on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a Scale(Baseline (week 0) to week 52)
- Change in haemoglobin (Hb)(Baseline (week 0) to week 52)
- Change in lactate dehydrogenase (LDH)(Baseline (week 0) to week 52)
- Change in absolute reticulocyte count(Baseline (week 0) to week 52)
- Change in indirect bilirubin(Baseline (week 0) to week 52)
- Change in Haemoglobin (Hb) greater than 1 grams per decilitre (g/dL)(Baseline (week 0) to week 24)
- Time to onset of first adjudicated Vaso-occlusive crisis (VOC)(Baseline (week 0) to week 52)
- Change in standardised T-score on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a Scale(Baseline (week 0) to week 52)
- Change in haemoglobin (Hb)(Baseline (week 0) to week 52)
- Change in lactate dehydrogenase (LDH)(Baseline (week 0) to week 52)
- Change in absolute reticulocyte count(Baseline (week 0) to week 52)
- Change in indirect bilirubin(Baseline (week 0) to week 52)
- Change in distance travelled during the 6-minute walking test (6MWT)(Baseline (week 0) to week 52)
- Participants achieving the threshold for clinically meaningful change (yes/no) in PROMIS fatigue scale 7a(Baseline (week 0) to week 52)
- Participants achieving the threshold for clinically meaningful change (yes/no) in 6MWT(Baseline (week 0) to week 52)
Investigators
Study Sites (317)
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