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/S316 sites in 3 countries408 target enrollmentFebruary 17, 2025

ConditionsSickle Cell Disease

InterventionsEtavopivat Placebo

DrugsEtavopivat Placebo

Overview

Phase: Phase 3
Intervention: Etavopivat
Conditions: Sickle Cell Disease
Sponsor: Novo Nordisk A/S
Enrollment: 408
Locations: 316
Primary Endpoint: Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact
Status: Recruiting
Last Updated: 8 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

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.

Registry

clinicaltrials.gov

Start Date

February 17, 2025

End Date

March 12, 2029

Last Updated

8 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novo Nordisk A/S

Responsible Party

Sponsor

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

Arms & Interventions

Etavopivat

Participants will be randomised to receive oral dose of Etavopivat.

Intervention: Etavopivat

Placebo

Participants will be randomised to receive oral dose of placebo.

Intervention: Placebo

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)