An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral Etavopivat, a Pyruvate Kinase Activator in Patients With Sickle Cell Disease (HIBISCUS)

About the study

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).

Study point of contact

Vandy Black, MD
857-209-2236
4202medicalmonitor@formatherapeutics.com

Locations

42 United States sites

4 France sites

4 Spain sites

2 Canada sites

2 Germany sites

2 Italy sites

1 United Kingdom site

Age

12 Years - 65 Years

Phase

Phase 2/Phase 3

Study type

Interventional

Gender

All

Interventions

Drug

participation requirements

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

participation restrictions

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)

Locations

  • Birmingham, Alabama, United States, University of Alabama at Birmingham (UAB), 35249 [Recruiting]
  • Phoenix, Arizona, United States, Phoenix Children's Hospital, 85016 [Recruiting]
  • Little Rock, Arkansas, United States, Woodland International Research Group, 72211 [Recruiting]
  • Long Beach, California, United States, Collaborative Neuroscience Research, LLC., 90806 [Recruiting]
  • Oakland, California, United States, Pacific Research Partners, LLC, 94607 [Terminated]
  • Sacramento, California, United States, UC Davis Medical Center - UC Davis Comprehensive Cancer Center - Hemotology/Oncology Clinic, 95817 [Recruiting]
  • Farmington, Connecticut, United States, University of Connecticut (UCONN) Health, 06030 [Recruiting]
  • Washington, District of Columbia, United States, Children's National Health Center, 20010 [Recruiting]
  • Washington, District of Columbia, United States, Howard University, 20060 [Terminated]
  • Altamonte Springs, Florida, United States, Cornerstone Research Institute, 32701 [Terminated]
  • Hollywood, Florida, United States, Foundation for Sickle Cell Disease Research, 33021 [Recruiting]
  • Miami, Florida, United States, Advanced Pharma CR LLC., 33147 [Recruiting]
  • Atlanta, Georgia, United States, Emory University School of Medicine, 30322 [Recruiting]
  • Atlanta, Georgia, United States, Sonar Clinical Research, 30331 [Recruiting]
  • Atlanta, Georgia, United States, Children's Healthcare of Atlanta - Pediatric Research Center, 30342 [Recruiting]
  • Augusta, Georgia, United States, Augusta University Center for Blood Disorders., 30912 [Recruiting]
  • Chicago, Illinois, United States, University of Illinois at Chicago Sickle Cell Center, 60612 [Recruiting]
  • New Orleans, Louisiana, United States, Children's Hospital New Orleans, 70118 [Recruiting]
  • Baltimore, Maryland, United States, University of Maryland School of Medicine, 21201 [Recruiting]
  • Boston, Massachusetts, United States, Boston Medical Center, 02118 [Recruiting]
  • Detroit, Michigan, United States, Barbara Ann Karmanos Cancer Institute, 48201 [Recruiting]
  • Saint Louis, Missouri, United States, Washington University School of Medicine Barnes - Jewish Hospital, 63110 [Recruiting]
  • Omaha, Nebraska, United States, University of Nebraska Medical Center, 68198 [Recruiting]
  • Bronx, New York, United States, Jacobi Medical Center, 10461 [Recruiting]
  • Bronx, New York, United States, Children's Hospital at Montefiore, 10467 [Recruiting]
  • Brooklyn, New York, United States, Kings County Hospital, 11203 [Recruiting]
  • Jamaica, New York, United States, Queens Hospital Center, 11432 [Recruiting]
  • New York, New York, United States, Colombia University Medical Center, 10032 [Recruiting]
  • Chapel Hill, North Carolina, United States, UNC School of Medicine, 27514 [Recruiting]
  • Durham, North Carolina, United States, Duke University - Sickle Cell Center, 27705 [Recruiting]
  • Greenville, North Carolina, United States, East Carolina University (ECU) Physicians, 27834 [Recruiting]
  • Cincinnati, Ohio, United States, University of Cincinnati Cancer Center, 45219 [Recruiting]
  • Cincinnati, Ohio, United States, Cincinnati Childrens Hospital Medical Center, 45229 [Recruiting]
  • North Canton, Ohio, United States, Neuro-Behavioral Clinical Research, 44720 [Recruiting]
  • Tulsa, Oklahoma, United States, Lynn Institute of Tulsa, 74135 [Recruiting]
  • Philadelphia, Pennsylvania, United States, Thomas Jefferson University Hospital, 19107 [Recruiting]
  • Charleston, South Carolina, United States, Medical University of South Carolina (MUSC), 29425 [Recruiting]
  • Greenville, South Carolina, United States, Prisma Health, 29605 [Recruiting]
  • Memphis, Tennessee, United States, St. Jude Children's Research Hospital (SJCRH), 38105 [Recruiting]
  • Nashville, Tennessee, United States, Methodist University Hospital, 38104 [Recruiting]
  • Houston, Texas, United States, The University of Texas Health Science Center at Houston, 77030 [Recruiting]
  • Tacoma, Washington, United States, Mary Bridge Children's Health Center, 98405 [Recruiting]
  • Montréal, Canada, Universite de Montreal - Centre Hospitalier Universitaire (CHU) Sainte-Justine, H3T 1C5 [Recruiting]
  • Toronto, Canada, The Hospital for Sick Children, M5G 1X8 [Recruiting]
  • Montpellier, Montpellier Cedex 5, France, CHU Montpellier, Hôpital Saint-Eloi, 34295 [Recruiting]
  • Lyon, France, Hôpital Edouard HERRIOT, 69437 [Recruiting]
  • Mulhouse, France, Hôpital Emile Muller, 68100 [Recruiting]
  • Paris, France, CHU Paris - Hôpital Robert Debré [Recruiting]
  • Freiburg, Germany, Universitätsklinikum Freiburg, 79106 [Recruiting]
  • Heidelberg, Germany, University Hospital of Heidelberg, 69120 [Recruiting]
  • Orbassano, Italy, Azienda Ospedaliera Universitaria San Luigi Gonzaga, 10043 [Recruiting]
  • Padova, Italy, Azienda Ospedale Università Padova, 35128 [Recruiting]
  • Barakaldo, Spain, Hospital De Cruces, 48013 [Recruiting]
  • Barcelona, Spain, Hospital Universitari Vall d'Hebron de Barcelona, 08035 [Recruiting]
  • Madrid, Spain, Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz, 28046 [Recruiting]
  • Sevilla, Spain, Hospital Universitario Virgen del Rocio, 41013 [Recruiting]
  • London, United Kingdom, Guy's and St Thomas' NHS Foundation Trust, SE18 3RA [Recruiting]
Last updated 2022-09-29