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

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.
Brief Title
A Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease
Central Contacts
Central Contact Role
Contact
Central Contact Phone
(+1) 866-867-7178
Central Contact Email
clinicaltrials@novonordisk.com
Completion Date
Completion Date Type
Estimated
Conditions
Sickle Cell Disease
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.
Inclusion 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.

Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT06612268
Org Class
Industry
Org Full Name
Novo Nordisk A/S
Org Study Id
NN7535-7807
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Description
Measured as Count of events.
Outcome Measure
Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact
Outcome Time Frame
Baseline (week 0) to week 52
Secondary Ids
Secondary Id
U1111-1298-3431
Secondary Id
2023-509175-16
Secondary Outcomes
Outcome Description
Measured as time in days.
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Time to onset of first adjudicated Vaso-occlusive crisis (VOC)
Outcome Description
Measured in Meters.
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in distance travelled during the 6-minute walking test (6MWT)
Outcome Description
Measured in T-score.
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in standardised T-score on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a Scale
Outcome Description
Measured in grams per decilitre (g/dL).
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in haemoglobin (Hb)
Outcome Description
Measured in Count of participants.
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in Haemoglobin (Hb) greater than 1 grams per decilitre (g/dL)
Outcome Description
Measured in Units per litre (U/L).
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in lactate dehydrogenase (LDH)
Outcome Description
Measured as Cells x10\^9/L.
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in absolute reticulocyte count
Outcome Description
Measured in milligrams per decilitre (mg/dL).
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in indirect bilirubin
Outcome Description
Measured in millilitre per minute per 1.73m\^2 (mL/min/ 1.73 m\^2).
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Changes in estimated glomerular filtration rate (eGFR)
Outcome Description
Measured in Percent (%).
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in albumin:creatinine ratio (ACR)
Outcome Description
Measured as Count of participants.
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Occurrence of moderate/severe albuminuria (yes/no)
Outcome Description
Measured in picograms per millilitre (pg/mL).
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Change in N-terminal pro b-type natriuretic peptide (NT-pro-BNP)
Outcome Description
Measured as Count of participants.
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Proportion of participants achieving the threshold for clinically meaningful change (yes/no) in PROMIS fatigue scale 7a
Outcome Description
Measured as Count of participants.
Outcome Time Frame
Baseline (week 0) to week 52
Outcome Measure
Proportion of participants achieving the threshold for clinically meaningful change (yes/no) in 6MWT
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Kaitlin Strumph
Investigator Email
kstrumph@montefiore.org
Investigator Department
Pediatrics
Investigator Division
Pediatric Hematology-Oncology
Investigator Sponsor Organization
External
Study Department
Pediatrics
Study Division
Pediatrics Hematology (non-malignant)
Categories Mesh Debug
Blood Disorders --- ANEMIA, SICKLE CELL
Sickle Cell Disorders --- ANEMIA, SICKLE CELL
Blood Disorders --- ANEMIA, HEMOLYTIC, CONGENITAL
Blood Disorders --- ANEMIA, HEMOLYTIC
Blood Disorders --- ANEMIA
Blood & Bone Marrow Cancers --- ANEMIA
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
MeSH Terms
ANEMIA, SICKLE CELL
ANEMIA, HEMOLYTIC, CONGENITAL
ANEMIA, HEMOLYTIC
ANEMIA
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
HEMOGLOBINOPATHIES
GENETIC DISEASES, INBORN
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES