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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04624659
Other study ID # 4202-HEM-301
Secondary ID
Status Recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date March 26, 2021
Est. completion date December 2026

Study information

Verified date April 2024
Source Novo Nordisk A/S
Contact Novo Nordisk
Phone (+1) 866-867-7178
Email clinicaltrials@novonordisk.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This clinical trial is a Phase 2/3 study that will evaluate the efficacy and safety of etavopivat and test how well etavopivat works compared to placebo to improve the amount of hemoglobin in the blood and to reduce the number of vaso-occlusive crises (times when the blood vessels become blocked and cause pain).


Description:

Etavopivat is designed to activate PKR and thereby modulate RBC metabolism by impacting two critical pathways in RBCs. The etavopivat clinical development program will investigate whether decreasing 2,3-DPG may help oxygen bind to hemoglobin (i.e. increasing oxygen affinity), and thereby increase ATP and impact RBC function. This study is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study of patients age 12 to 65 years (inclusive), with sickle cell disease. There are two planned interim analyses in this study design. Initially, patients will be randomized at 1:1:1 to one of two dose levels of etavopivat or placebo. At the first interim analysis, one of the two etavopivat dose levels will be selected for the Phase 3 portion of the study, in which patients will be randomized at 1:1 to the selected etavopivat dose or placebo. Efficacy on hemoglobin will be evaluated at the second interim analysis, and then will be tested along with evaluation of efficacy on vaso-occlusive crises at the final analysis. Following completion of 52 weeks of double-blind treatment, patients may enter a 52-week etavopivat open-label extension period.


Recruitment information / eligibility

Status Recruiting
Enrollment 344
Est. completion date December 2026
Est. primary completion date December 2025
Accepts healthy volunteers No
Gender All
Age group 12 Years to 65 Years
Eligibility Key Inclusion Criteria: - Provision of consent - Patient has a confirmed diagnosis of sickle cell disease - At least 2 episodes of vaso-occlusive crises in the past 12 months - Hemoglobin = 5.5 and = 10.5 g/dL (= 55 and = 105 g/L) during screening - Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 days prior to start of study treatment - Patients on crizanlizumab or L-glutamine treatment at the time of consent must be on a stable dose for = 12 months and must be = 80% compliant with the planned regimen at the time of consent and meet the VOC eligibility criteria - Female patients of childbearing potential must use highly effective methods of contraception, male patients are willing to use barrier methods of contraception Key Exclusion Criteria: - More than 10 vaso-occlusive crises within the past 12 months - Female who is breastfeeding or pregnant - Hepatic dysfunction characterized by: - Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) - Direct bilirubin > 3.0 × ULN - Known HIV positivity - Active hepatitis B or hepatitis C infection - Severe renal dysfunction or on chronic dialysis - History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following: - Unstable angina pectoris or myocardial infarction or elective coronary intervention - Congestive heart failure requiring hospitalization - Uncontrolled clinically significant arrhythmias - Symptomatic pulmonary hypertension - History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage - History of deep venous thrombosis requiring systemic anti-coagulation therapy for = 6 weeks, occurring within 6 months prior to Day 1 of study treatment. Prior/Concomitant Therapy - Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) - Receiving or use of concomitant medications that are strong inducers of CYP3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study - Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study - Use of an experimental selectin antagonist (eg, monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study - Use of erythropoietin or other hematopoietic 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 (eg, hematopoietic cell transplant, gene modification therapy)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Etavopivat Tablets Low dose
200 mg once daily
Etavopivat Tablets High dose
400 mg once daily
Placebo Tablets
Placebo once daily
Etavopivat Tablets
Selected dose once daily

Locations

Country Name City State
Canada Universite de Montreal - Centre Hospitalier Universitaire (CHU) Sainte-Justine Montréal
Canada The Hospital for Sick Children Toronto
Canada Providence Hematology Vancouver
France Hôpital Henri Mondor Créteil
France Hôpital Edouard HERRIOT Lyon
France CHU Montpellier, Hôpital Saint-Eloi Montpellier Montpellier Cedex 5
France Hôpital Emile Muller Mulhouse
France CHU Paris - Hôpital Robert Debré Paris
Germany Universitätsklinikum Freiburg Freiburg
Germany University Hospital of Heidelberg Heidelberg
Greece Hippocratio General Hospital Athens
Greece General University Hospital of Larissa Larissa
Greece General University Hospital of Patras Rio Patras
Greece General Hospital of Thessaloniki "Hippokration" Thessaloniki
Italy Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco" Catania
Italy Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
Italy Azienda Ospedale Università Padova Padova
Italy Fondazione IRCCS Policlinico San Matteo Pavia
Lebanon American University of Beirut Medical Center Beirut
Lebanon Nini Hospital Tripoli
Oman Sultan Qaboos University Hospital Muscat
Oman Sultan Qaboos University Hospital Muscat
Spain Hospital De Cruces Barakaldo
Spain Hospital Universitari Vall d'Hebron de Barcelona Barcelona
Spain Hospital Clínico San Carlos Madrid
Spain Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz Madrid
Spain Hospital Universitario Virgen del Rocio Sevilla
United Kingdom Leicester Royal Infirmary Leicester
United Kingdom Guy's and St Thomas' NHS Foundation Trust London
United Kingdom Hammersmith Hospital - Imperial College Healthcare NHS Trust London
United Kingdom Imperial College Healthcare NHS Trust - St Mary's Hospital London
United Kingdom King's College Hospital London
United Kingdom Oxford University Hospitals NHS Trust - Churchill Hospital - Cancer and Haematology Centre Oxford
United Kingdom The Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust Sheffield
United States Cornerstone Research Institute Altamonte Springs Florida
United States Children's Healthcare of Atlanta - Pediatric Research Center Atlanta Georgia
United States Emory University School of Medicine Atlanta Georgia
United States Sonar Clinical Research Atlanta Georgia
United States Augusta University Center for Blood Disorders. Augusta Georgia
United States University of Maryland School of Medicine Baltimore Maryland
United States University of Alabama at Birmingham (UAB) Birmingham Alabama
United States Boston Medical Center Boston Massachusetts
United States Children's Hospital at Montefiore Bronx New York
United States Jacobi Medical Center Bronx New York
United States Kings County Hospital Brooklyn New York
United States UNC School of Medicine Chapel Hill North Carolina
United States Medical University of South Carolina (MUSC) Charleston South Carolina
United States Levine Cancer Institute Charlotte North Carolina
United States University of Illinois at Chicago Sickle Cell Center Chicago Illinois
United States Cincinnati Childrens Hospital Medical Center Cincinnati Ohio
United States University of Cincinnati Cancer Center Cincinnati Ohio
United States iResearch Atlanta, LLC Decatur Georgia
United States Barbara Ann Karmanos Cancer Institute Detroit Michigan
United States Duke University - Sickle Cell Center Durham North Carolina
United States University of Connecticut (UCONN) Health Farmington Connecticut
United States East Carolina University (ECU) Physicians Greenville North Carolina
United States Prisma Health Greenville South Carolina
United States Office of Gershwin T. Blyden, MD Hollywood Florida
United States Baylor College of Medicine Houston Texas
United States The University of Texas Health Science Center at Houston Houston Texas
United States University of California, Irvine Irvine California
United States Queens Hospital Center Jamaica New York
United States Woodland International Research Group Little Rock Arkansas
United States Collaborative Neuroscience Research, LLC. Long Beach California
United States St. Jude Children's Research Hospital (SJCRH) Memphis Tennessee
United States Advanced Pharma CR LLC. Miami Florida
United States University of Miami - Miller School of Medicine Miami Florida
United States Blood Center of Wisconsin (BCW) Milwaukee Wisconsin
United States Methodist University Hospital Nashville Tennessee
United States Yale University New Haven Connecticut
United States Long Island Jewish Medical Center New Hyde Park New York
United States Children's Hospital New Orleans New Orleans Louisiana
United States Columbia University Medical Center New York New York
United States Neuro-Behavioral Clinical Research North Canton Ohio
United States Pacific Research Partners, LLC Oakland California
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States University of Nebraska Medical Center Omaha Nebraska
United States Arnold Palmer Hospital for Children - Haley Center for Children's Cancer and Blood Disorders Orlando Florida
United States Thomas Jefferson University Hospital Philadelphia Pennsylvania
United States Phoenix Children's Hospital Phoenix Arizona
United States UC Davis Medical Center - UC Davis Comprehensive Cancer Center - Hemotology/Oncology Clinic Sacramento California
United States Washington University School of Medicine Barnes - Jewish Hospital Saint Louis Missouri
United States Mary Bridge Children's Health Center Tacoma Washington
United States Lynn Institute of Tulsa Tulsa Oklahoma
United States Children's National Health Center Washington District of Columbia
United States Howard University Washington District of Columbia
United States Wake Forest Baptist Medical Center Winston-Salem North Carolina

Sponsors (2)

Lead Sponsor Collaborator
Forma Therapeutics, Inc. Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Greece,  Italy,  Lebanon,  Oman,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Hemoglobin response rate Hemoglobin response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period 24 Weeks
Primary Annualized vaso-occlusive crisis Annualized vaso-occlusive crisis rate during the 52-week blinded treatment period based on adjudicated vaso-occlusive crisis review 52 Weeks
Secondary Hemoglobin Change from baseline in hemoglobin at Week 24 during the blinded treatment period 24 Weeks
Secondary Hemoglobin Change from baseline in hemoglobin at Week 52 during the blinded treatment period 52 Weeks
Secondary Absolute reticulocyte count Change in absolute reticulocyte count from baseline at Week 24 during the blinded treatment period 24 Weeks
Secondary Unconjugated bilirubin Change in unconjugated bilirubin from baseline at Week 24 during the blinded treatment period 24 Weeks
Secondary Lactate dehydrogenase Change in lactate dehydrogenase from baseline at Week 24 during the blinded treatment period 24 Weeks
Secondary Vaso-occlusive crisis Time to first vaso-occlusive crisis during the blinded treatment period 52 Weeks
Secondary Patient-Reported Outcome Measurement Information System (PROMIS) Change in PROMIS Fatigue Scale from baseline in adult patients at Week 24 during the blinded treatment period 24 Weeks
Secondary Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale Change in PROMIS Fatigue Scale from baseline in adult patients at Week 52 during the blinded treatment period 52 Weeks
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