Sickle Cell Disease Clinical Trial
Official title:
An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral Etavopivat, a Pyruvate Kinase Activator in Patients With Sickle Cell Disease (HIBISCUS)
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).
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) |
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 |
Lead Sponsor | Collaborator |
---|---|
Forma Therapeutics, Inc. | Novo Nordisk A/S |
United States, Canada, France, Germany, Greece, Italy, Lebanon, Oman, Spain, United Kingdom,
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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