A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)
- Conditions
- Sickle Cell Disease
- Interventions
- Registration Number
- NCT04624659
- Lead Sponsor
- Forma Therapeutics, Inc.
- Brief 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).
- Detailed 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 is one 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 conclusion of the double-blind treatment period. Following completion of 52 weeks of double-blind treatment, patients may enter a 112-week etavopivat open-label extension period.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 450
- 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
-
More than 15 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double blind etavopivat Low Dose Etavopivat Tablets Low dose Double blind etavopivat Low Dose Double blind etavopivat High Dose Etavopivat Tablets High dose Double blind etavopivat High Dose Double blind placebo Placebo Tablets Double blind placebo Open label etavopivat Etavopivat Tablets Open label etavopivat
- Primary Outcome Measures
Name Time Method Hemoglobin response rate 24 Weeks Hemoglobin response rate at Week 24 (increase of \> 1 g/dL \[\> 10 g/L\] from baseline) during the blinded treatment period
Annualized vaso-occlusive crisis 52 Weeks Annualized vaso-occlusive crisis rate during the 52-week blinded treatment period based on adjudicated vaso-occlusive crisis review
- Secondary Outcome Measures
Name Time Method Hemoglobin 52 Weeks Change from baseline in hemoglobin at Week 52 during the blinded treatment period
Absolute reticulocyte count 24 Weeks Change in absolute reticulocyte count from baseline at Week 24 during the blinded treatment period
Indirect bilirubin 24 Weeks Change in unconjugated bilirubin from baseline at Week 24 during the blinded treatment period
Lactate dehydrogenase 24 Weeks Change in lactate dehydrogenase from baseline at Week 24 during the blinded treatment period
Vaso-occlusive crisis 52 Weeks Time to first vaso-occlusive crisis during the blinded treatment period
Fatigue 52 Weeks Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale from baseline in adult patients at Week 52 during the blinded treatment period
Trial Locations
- Locations (215)
Hospices Civils de Lyon-Hopital Edouard Herriot
🇫🇷Lyon, France
Univertatsklinikum Frankfurt
🇩🇪Frankfurt, Germany
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
[Legal] Baylor College of Medicine
🇺🇸Houston, Texas, United States
Univ of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham (UAB)
🇺🇸Birmingham, Alabama, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Phoenix Children's Hsptl
🇺🇸Phoenix, Arizona, United States
[Legal] Woodland International Research Group, LLC
🇺🇸Little Rock, Arkansas, United States
Woodland International Research Group
🇺🇸Little Rock, Arkansas, United States
University of California, Irvine
🇺🇸Irvine, California, United States
[Legal] Collaborative Neuroscience Network, LLC
🇺🇸Long Beach, California, United States
Collaborative Neuroscience Research, LLC.
🇺🇸Long Beach, California, United States
Pacific Research Partners, LLC
🇺🇸Oakland, California, United States
Pacific Research Partners
🇺🇸Oakland, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
UCSF Oakland Benioff ChildHosp
🇺🇸Oakland, California, United States
University Of California Irvine
🇺🇸Orange, California, United States
UC Davis Medical Center - UC Davis Comprehensive Cancer Center - Hemotology/Oncology Clinic
🇺🇸Sacramento, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
University of Connecticut (UCONN) Health
🇺🇸Farmington, Connecticut, United States
University of Connecticut
🇺🇸Farmington, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Children's National Health Center
🇺🇸Washington, District of Columbia, United States
Howard University
🇺🇸Washington, District of Columbia, United States
Cornerstone Research Institute
🇺🇸Altamonte Springs, Florida, United States
University of Florida Hematology
🇺🇸Gainesville, Florida, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Office of Gershwin T. Blyden, MD
🇺🇸Hollywood, Florida, United States
Foundation for Sickle Cell Disease Research
🇺🇸Hollywood, Florida, United States
University of Miami - Miller School of Medicine
🇺🇸Miami, Florida, United States
University Of Miami
🇺🇸Miami, Florida, United States
Advanced Pharma CR LLC.
🇺🇸Miami, Florida, United States
Advanced Pharma CR
🇺🇸Miami, Florida, United States
Arnold Palmer Children's Hospital
🇺🇸Orlando, Florida, United States
Arnold Palmer Hospital for Children - Haley Center for Children's Cancer and Blood Disorders
🇺🇸Orlando, Florida, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Sonar Clinical Research
🇺🇸Atlanta, Georgia, United States
Children's Healthcare of Atlanta - Pediatric Research Center
🇺🇸Atlanta, Georgia, United States
Children's Healthcare of Atlanta Investigational Medication Pharmacy
🇺🇸Atlanta, Georgia, United States
Augusta University Center for Blood Disorders.
🇺🇸Augusta, Georgia, United States
Center for Blood Disorders Augusta University
🇺🇸Augusta, Georgia, United States
iResearch Atlanta, LLC
🇺🇸Decatur, Georgia, United States
University of Illinois at Chicago Sickle Cell Center
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Children's Hosp-New Orleans
🇺🇸New Orleans, Louisiana, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital_Boston
🇺🇸Boston, Massachusetts, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Detroit Medical Center (DMC) - Children's Hospital of Michigan (CHM)
🇺🇸Detroit, Michigan, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Washington University School of Medicine Barnes - Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine_St. Louis
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Children's National Health Hospital
🇺🇸Washington, New Jersey, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Kings County Hospital
🇺🇸Brooklyn, New York, United States
NYC Health+Hospitals
🇺🇸Brooklyn, New York, United States
Queens Hospital Center
🇺🇸Jamaica, New York, United States
North Shore Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Columbia University Medical Center_New York
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Weill Cornell Med Coll-NYPH
🇺🇸New York, New York, United States
[Legal] The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
UNC School of Medicine
🇺🇸Chapel Hill, North Carolina, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Duke University - Sickle Cell Center
🇺🇸Durham, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
East Carolina University (ECU) Physicians
🇺🇸Greenville, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
University of Cincinnati Cancer Center
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
[Legal] Children's Hospital Medical Center dba Cincinnati Children's
🇺🇸Cincinnati, Ohio, United States
Cincinnati Childrens Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
The Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Neuro-Behavioral Clinical Research
🇺🇸North Canton, Ohio, United States
Jimmy Everest Cancer Hematology & Oncology
🇺🇸Oklahoma City, Oklahoma, United States
Lynn Institute of Tulsa
🇺🇸Tulsa, Oklahoma, United States
Children's Hosptl Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
The Children's Hospital of Philadelphia (CHOP)
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Prisma Health-Upstate
🇺🇸Greenville, South Carolina, United States
Prisma Health
🇺🇸Greenville, South Carolina, United States
Methodist University Hospital
🇺🇸Nashville, Tennessee, United States
[Legal] St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
St. Jude Children's Research Hospital (SJCRH)
🇺🇸Memphis, Tennessee, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
UT Health University of Texas
🇺🇸Houston, Texas, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Mary Bridge Children's Health Center
🇺🇸Tacoma, Washington, United States
Mary Bridge Children's Health
🇺🇸Tacoma, Washington, United States
Blood Center of Wisconsin (BCW)
🇺🇸Milwaukee, Wisconsin, United States
Versiti Blood Center of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Providence Hematolgy
🇨🇦Vancouver, British Columbia, Canada
The Hospital for Sick Children
🇨🇦Toronto, Canada
University Health Network - Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
CHU Sainte-Justine Mother and Child University Hospital
🇨🇦Montreal, Quebec, Canada
Universite de Montreal - Centre Hospitalier Universitaire (CHU) Sainte-Justine
🇨🇦Montréal, Canada
University Health Network Toronto General Hospital
🇨🇦Toronto, Canada
Providence Hematology
🇨🇦Vancouver, Canada
[Legal] Alexandria Clinical Research LLC
🇪🇬Alexandria, Egypt
Alexandria Clinical Research Center
🇪🇬Alexandria, Egypt
Alexandria Faculty of Medicine - Clinical Research Center
🇪🇬Alexandria, Egypt
Ain Shams University Hospital
🇪🇬Cairo, Egypt
Cairo University
🇪🇬Cairo, Egypt
Al Kasr AL Aini Hospital
🇪🇬Cairo, Egypt
Sydnawy University Hospital
🇪🇬Zagazig, Egypt
CHU Montpellier, Hôpital Saint-Eloi
🇫🇷Montpellier, Montpellier Cedex 5, France
Ap-Hp-Hopital Henri Mondor
🇫🇷Creteil, France
Hôpital Henri Mondor
🇫🇷Créteil, France
Hôpital Edouard HERRIOT
🇫🇷Lyon, France
Centre Hospitalier Universitaire de Montpellier-Hopital Saint-Eloi
🇫🇷Montpellier Cedex 5, France
GHR Mulhouse Sud-Alsace
🇫🇷Mulhouse, France
Hôpital Emile Muller
🇫🇷Mulhouse, France
Ap-Hp-Hopital Robert Debre
🇫🇷Paris, France
CHU Paris - Hôpital Robert Debré
🇫🇷Paris, France
Saint-Denis Hospital Center
🇫🇷Saint-Denis, France
Charité - Campus Virchow-Klinikum - Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie
🇩🇪Berlin, Germany
Charite Berlin - University Medicine
🇩🇪Berlin, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt am Main, Germany
Universitätsklinikum Freiburg-Zentrum für Kinder- und Jugendmedizin
🇩🇪Freiburg, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
University Medical Center Hamburg-Eppendorf
🇩🇪Hamburg, Germany
UKE Hamburg
🇩🇪Hamburg, Germany
Uniklinik Heidelberg - Klinik für Pädiatrische Onkologie, Hämatologie, Immunologie und Pneumologie
🇩🇪Heidelberg, Germany
University Hospital of Heidelberg
🇩🇪Heidelberg, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Universitatsklinikum Regensburg
🇩🇪Regensburg, Germany
Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital (KBTH)
🇬🇭AccrA, Ghana
Kintampo Health Research Centre (KHRC), Kintampo, Ghana
🇬🇭Kintampo, Ghana
General University Hospital of Patras
🇬🇷Rio, Patras, Greece
Gen Hosp Athens Ippokrateio,B' Uni Clinic Internal Medicine
🇬🇷Athens, Greece
Hippocratio General Hospital
🇬🇷Athens, Greece
General Hospital Of Larissa Koutlibaneio And Triantafylleio
🇬🇷Larissa, Greece
General University Hospital of Larissa
🇬🇷Larissa, Greece
'Ippokrateio' General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
General Hospital of Thessaloniki "Hippokration"
🇬🇷Thessaloniki, Greece
K.J Somaiya Hospital and Research Centre
🇮🇳Mumbai, Maharashtra, India
Victoria Hospital, Bangalore
🇮🇳Bangalore, India
Srirama Chandra Bhanj Medical College & Hospital (S.C.B Medical College)
🇮🇳Cutack, India
Yashoda Hospital
🇮🇳Hyderabad, India
All India Institute of Medical Sciences (AIIMS)
🇮🇳New Delhi, India
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, PV, Italy
Azienda Ospedaliero Universitaria Policlinico "G. Rodolico - San Marco"
🇮🇹Catania, Italy
Azienda Ospedaliero Universitaria Policlinico G. Rodolico - San Marco
🇮🇹Catania, Italy
Azienda Ospedaliera Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Italy
Azienda Ospedale Universita Padova
🇮🇹Padova, Italy
Azienda Ospedale Università Padova
🇮🇹Padova, Italy
ARNAS Ospedali Civico Di Cristina Benfratelli
🇮🇹Palermo, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Ospedale Pediatrico Bambino Ges
🇮🇹Roma, Italy
IRCCS Ospedale Pediatrico Bambino Gesu
🇮🇹Rome, Italy
Kombewa Clinical Research Centre
🇰🇪Kisumu, Kenya
KEMRI Kondele Children Hospital, Kisumu
🇰🇪Kisumu, Kenya
KEMRI Siaya Clinical Research Annex Siaya County Referral Hospital, Siaya
🇰🇪Kisumu, Kenya
Gertrude's Children's Hospital, Nairobi
🇰🇪Nairobi, Kenya
American University of Beirut Medical center
🇱🇧Beirut, Lebanon
American University of Beirut Medical Center
🇱🇧Beirut, Lebanon
Hospital Nini
🇱🇧Tripoli, Lebanon
Nini Hospital
🇱🇧Tripoli, Lebanon
University of Abuja Teaching Hospital, Gwagwalada, Abuja
🇳🇬Abuja, Nigeria
Barau Dikko Teaching Hospital, Kaduna
🇳🇬Kaduna, Nigeria
Aminu Kano Teaching Hospital (AKTH)
🇳🇬Kano, Nigeria
Lagos University Teaching Hospital, Lagos
🇳🇬Lagos, Nigeria
University of Nigeria Teaching Hospital, Enugu
🇳🇬Lagos, Nigeria
Sultan Qaboos University Hospital
🇴🇲Muscat, Oman
King Fahad Specialist Hospital-Dammam
🇸🇦Damman, Saudi Arabia
Prince Mohammad Bin Naser Hospital
🇸🇦Jazan, Saudi Arabia
King Khaled University Hospital,King Saud Univ. Med. City
🇸🇦Riyadh, Saudi Arabia
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital Universitario de Cruces
🇪🇸Baracaldo, Spain
Hospital De Cruces
🇪🇸Barakaldo, Spain
Hospital Universitari Vall d'Hebron de Barcelona
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Sant Joan de Déu
🇪🇸Barcelona, Spain
Complejo Hospitalario Universitario A Coruña
🇪🇸La Coruna, Spain
Hospital Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Cukurova Universitesi
🇹🇷Adana, Turkey
Baskent Universitesi Adana
🇹🇷Adana, Turkey
Adana City Training and Research Hospital
🇹🇷Adana, Turkey
Hacettepe Universitesi
🇹🇷Ankara, Turkey
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Mersin University Medical Faculty Hospital, Hematology
🇹🇷Mersin, Turkey
VM Medical Park Mersin Hospital
🇹🇷Mersin, Turkey
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
University Hospital Lewisham, Lewisham and Greenwich NHS Trust
🇬🇧London, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom
Guys and St Thomas NHS Foundation Trust / Evelina Childrens Hospital
🇬🇧London, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Hammersmith Hospital - Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust - Hammersmith Hospital
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust - St Mary's Hospital
🇬🇧London, United Kingdom
Churchill Hospital
🇬🇧Oxford, 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 Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom