A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS) (HIBISCUS)

March 31, 2026 updated by: Forma Therapeutics, Inc.

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

450

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6E 1M7
        • Providence Hematolgy
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children
      • Toronto, Ontario, Canada, M5G 2C4
        • University Health Network - Toronto General Hospital
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • CHU Sainte-Justine Mother and Child University Hospital
  • Egypt
      • Alexandria, Egypt
        • [Legal] Alexandria Clinical Research LLC
      • Alexandria, Egypt, 21131
        • [Legal] Alexandria Clinical Research LLC
      • Cairo, Egypt, 1181
        • Ain shams university hospital
      • Cairo, Egypt, 111111
        • Cairo University
      • Cairo, Egypt, 11956
        • Al Kasr AL Aini Hospital
      • Zagazig, Egypt, 44519
        • Sydnawy University Hospital
  • France
      • Créteil, France, 94010
        • Ap-Hp-Hopital Henri Mondor
      • Lyon, France, 69437
        • Hospices Civils de Lyon-Hopital Edouard Herriot
      • Montpellier, France, 34295
        • Centre Hospitalier Universitaire de Montpellier-Hopital Saint-Eloi
      • Mulhouse, France, 68100
        • GHR Mulhouse Sud-Alsace
      • Paris, France, 75019
        • Ap-Hp-Hopital Robert Debre
      • Saint-Denis, France, 93200
        • Saint-Denis Hospital Center
  • Germany
      • Berlin, Germany, 13353
        • Charité - Campus Virchow-Klinikum - Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie
      • Frankfurt am Main, Germany, 60596
        • Universitatsklinikum Frankfurt
      • Freiburg im Breisgau, Germany, 79106
        • Universitätsklinikum Freiburg-Zentrum für Kinder- und Jugendmedizin
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf - University Medical Center Hamburg-Eppendorf
      • Heidelberg, Germany, 69120
        • Uniklinik Heidelberg - Klinik für Pädiatrische Onkologie, Hämatologie, Immunologie und Pneumologie
      • Regensburg, Germany, 93053
        • Universitätsklinikum Regensburg
  • Ghana
      • Accra, Ghana
        • Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital (KBTH)
    • Bono East
      • Kintampo, Bono East, Ghana, 27WF+98M
        • Kintampo Health Research Centre (KHRC)
  • Greece
      • Athens, Greece, 115 27
        • Gen Hosp Athens Ippokrateio,B' Uni Clinic Internal Medicine
      • Larissa, Greece, 41221
        • General Hospital Of Larissa Koutlibaneio And Triantafylleio - Thalassemia and SCD Unit
      • Thessaloniki, Greece, 54642
        • 'Ippokrateio' General Hospital of Thessaloniki
    • Larissa
      • Pátrai, Larissa, Greece, 265 04
        • General University Hospital of Patras
  • India
      • Bangalore, India, 560002
        • Victoria Hospital, Bangalore
      • Cutack, India, 753007
        • Srirama Chandra Bhanj Medical College & Hospital (S.C.B Medical College)
      • New Delhi, India, 110029
        • All India Institute of Medical Sciences (AIIMS)
    • Maharashtra
      • Mumbai, Maharashtra, India, 400022
        • K.J Somaiya Hospital and Research Centre
    • Telangana
      • Hyderabad, Telangana, India, 500084
        • Yashoda hospital
  • Italy
      • Catania, Italy, 95123
        • Azienda Ospedaliero Universitaria Policlinico G. Rodolico - San Marco
      • Orbassano, Italy, 10043
        • Azienda Ospedaliera Universitaria San Luigi Gonzaga - S.C.D.O. Microcitemie e malattie rare ematologiche
      • Padova, Italy, 35128
        • Azienda Ospedale Universita Padova
      • Palermo, Italy, 90127
        • ARNAS Ospedali Civico Di Cristina Benfratelli - Presidio Ospedaliero "Civio e Benfratelli"
      • Roma, Italy, 00165
        • Ospedale Pediatrico Bambino Ges
    • PV
      • Pavia, PV, Italy, 27100
        • Centro per lo Studio e la Cura delle Amiloidosi Sistemiche Fondazione IRCCS Policlinico San Matteo
  • Kenya
      • Kisumu, Kenya, 1932
        • Kombewa Clinical Research Centre
      • Kisumu, Kenya, 40100
        • KEMRI Kondele Children Hospital, Kisumu
      • Kisumu, Kenya, 40600
        • KEMRI CRDR Siaya Clinical Research Annex, Country Referral Hospital
      • Nairobi, Kenya, 100
        • Gertrude's Children's Hospital
  • Lebanon
      • Amman, Lebanon, 11844
        • Master Centre for Lebanon
      • Beirut, Lebanon, 11-0236
        • American University of Beirut Medical Center
      • Tripoli, Lebanon, 113-6044
        • Hospital Nini
  • Nigeria
      • Abuja, Nigeria, 228
        • University of Abuja Teaching Hospital, Gwagwalada, Abuja
      • Kaduna, Nigeria, 800212
        • Barau Dikko Teaching Hospital, Kaduna
      • Kano, Nigeria, 3452
        • Aminu Kano Teaching Hospital (AKTH)
      • Lagos, Nigeria, 102215
        • Lagos University Teaching Hospital, Lagos
      • Lagos, Nigeria, 102215
        • University of Nigeria Teaching Hospital (UNTH)
  • Oman
    • Sultanet of Oman/Muscat/Al Khoud
      • Muscat, Sultanet of Oman/Muscat/Al Khoud, Oman, 123
        • Sultan Qaboos University Hospital
  • Saudi Arabia
      • Dammam, Saudi Arabia, 32253
        • King Fahad Specialist Hospital-Dammam
      • Jizan, Saudi Arabia, 82943
        • Prince Mohammad Bin Naser Hospital
      • Riyadh, Saudi Arabia, 12372 6864
        • King Khaled University Hospital,King Saud Univ. Med. City
  • Spain
      • A Coruña, Spain, 15006
        • Complejo Hospitalario Universitario A Coruña
      • Badalona, Spain, 8916
        • Hospital Germans Trias i Pujol
      • Barakaldo, Spain, 48903
        • Hospital Universitario de Cruces
      • Barcelona, Spain, 08035
        • Hospital Vall d'Hebron
      • Barcelona, Spain, 8950
        • Hospital Sant Joan de Deu
      • Madrid, Spain, 28009
        • Hospital Gregorio Marañon
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 4522
        • Adana City Training and Research Hospital
      • Adana, Turkey (Türkiye), 1240
        • Başkent Üniversitesi Adana Dr. Turgut Noyan Uygulama ve Araştırma Merkezi
      • Adana, Turkey (Türkiye), 1130
        • Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji
      • Ankara, Turkey (Türkiye), 6230
        • Hacettepe Üniversitesi Hastanesi- Hematoloji
      • Izmir, Turkey (Türkiye), 35040
        • Ege Üniversitesi Tip Fakultesi Hastanesi - Nefroloji
      • Mersin, Turkey (Türkiye), 33110
        • Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji
      • Mersin, Turkey (Türkiye), 33200
        • VM Medical Park Mersin Hastanesi- Kardiyoloji
  • United Kingdom
      • Leicester, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary - Haemostasis & Thrombosis Unit
      • London, United Kingdom, SE13 6LH
        • University Hospital Lewisham, Lewisham and Greenwich NHS Trust
      • London, United Kingdom, SE18 3RA
        • Guys and St Thomas NHS Foundation Trust / Evelina Childrens Hospital
      • London, United Kingdom, SE5 9RS
        • Kings College Hospital - Haematology
      • London, United Kingdom, W2 1NY
        • Hammersmith Hospital - London
      • Oxford, United Kingdom, OX3 7LE
        • Churchill Hospital
      • Sheffield, United Kingdom, S11 8RN
        • Royal Hallamshire Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Univ of Alabama Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's Hsptl
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • [Legal] Woodland International Research Group, LLC
    • California
      • Long Beach, California, United States, 90806
        • [Legal] Collaborative Neuroscience Network, LLC
      • Oakland, California, United States, 94607
        • Pacific Research Partners
      • Oakland, California, United States, 94609
        • UCSF Oakland Benioff ChildHosp
      • Orange, California, United States, 92868
        • University of California Irvine
      • Sacramento, California, United States, 95817
        • UC Davis Medical Center
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale University
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20060
        • Howard University
      • Washington D.C., District of Columbia, United States, 20010
        • Children's National Health Hospital
    • Florida
      • Altamonte Springs, Florida, United States, 32701
        • Cornerstone Research Institute
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Hollywood, Florida, United States, 33023
        • Foundation for Sickle Cell Disease Research
      • Miami, Florida, United States, 33136
        • University of Miami
      • Miami, Florida, United States, 33147
        • Advanced Pharma CR
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Children's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Emory University School of Medicine
      • Atlanta, Georgia, United States, 30315
        • Sonar Clinical Research
      • Atlanta, Georgia, United States, 30342
        • Children's Healthcare of Atlanta Investigational Medication Pharmacy
      • Augusta, Georgia, United States, 30912
        • Center for Blood Disorders Augusta University
      • Decatur, Georgia, United States, 30030
        • iResearch Atlanta, LLC
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago
    • Louisiana
      • New Orleans, Louisiana, United States, 70118
        • Children's Hosp-New Orleans
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital_Boston
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48201
        • [Legal] Dr. Vince Clinical Research, LLC and Dr. Vince Clinical Research, P.A.
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine_St. Louis
    • Nebraska
      • Omaha, Nebraska, United States, 68198-2168
        • University of Nebraska Medical Center
    • New York
      • Brooklyn, New York, United States, 11203
        • NYC Health+Hospitals
      • Jamaica, New York, United States, 11432-1121
        • Queens Hospital Center
      • New Hyde Park, New York, United States, 11040
        • North Shore Long Island Jewish Medical Center
      • New York, New York, United States, 10065
        • Weill Cornell Med Coll-NYPH
      • New York, New York, United States, 10032
        • Columbia University Medical Center_New York
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • The Bronx, New York, United States, 10461
        • Jacobi Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • [Legal] The University of North Carolina at Chapel Hill
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Greenville, North Carolina, United States, 27858
        • East Carolina University
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Health
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati
      • Cincinnati, Ohio, United States, 45229
        • [Legal] Children's Hospital Medical Center dba Cincinnati Children's
      • Columbus, Ohio, United States, 43203
        • The Ohio State University Medical Center
      • North Canton, Ohio, United States, 44720
        • Neuro-Behavioral Clinical Research
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Jimmy Everest Cancer Hematology & Oncology
      • Tulsa, Oklahoma, United States, 74135
        • Lynn Institute of Tulsa
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hosptl Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213-4306
        • University of Pittsburgh Medical Center
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Greenville, South Carolina, United States, 29605
        • Prisma Health-Upstate
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Methodist University Hospital
      • Memphis, Tennessee, United States, 38105
        • [Legal] St. Jude Children's Research Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • UT Health University of Texas
      • Houston, Texas, United States, 77030
        • [Legal] Baylor College of Medicine
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Washington
      • Tacoma, Washington, United States, 98405
        • Mary Bridge Children's Health
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Versiti Blood Center of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Double blind etavopivat Low Dose
Drug: Etavopivat Tablets Low dose
200 mg once daily
Other Names:
  • FT-4202
Experimental: Double blind etavopivat High Dose
Drug: Etavopivat Tablets High dose
400 mg once daily
Other Names:
  • FT-4202
Experimental: Double blind placebo
Drug: Placebo Tablets
Placebo once daily
Other Names:
  • placebo
Experimental: Open label etavopivat
Drug: Etavopivat Tablets
Selected dose once daily
Other Names:
  • FT-4202

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemoglobin response rate
Time Frame: 24 Weeks
Hemoglobin response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period
24 Weeks
Annualized vaso-occlusive crisis
Time Frame: 52 Weeks
Annualized vaso-occlusive crisis rate during the 52-week blinded treatment period based on adjudicated vaso-occlusive crisis review
52 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemoglobin
Time Frame: 52 Weeks
Change from baseline in hemoglobin at Week 52 during the blinded treatment period
52 Weeks
Absolute reticulocyte count
Time Frame: 24 Weeks
Change in absolute reticulocyte count from baseline at Week 24 during the blinded treatment period
24 Weeks
Lactate dehydrogenase
Time Frame: 24 Weeks
Change in lactate dehydrogenase from baseline at Week 24 during the blinded treatment period
24 Weeks
Vaso-occlusive crisis
Time Frame: 52 Weeks
Time to first vaso-occlusive crisis during the blinded treatment period
52 Weeks
Indirect bilirubin
Time Frame: 24 Weeks
Change in unconjugated bilirubin from baseline at Week 24 during the blinded treatment period
24 Weeks
Fatigue
Time Frame: 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
52 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Forma Therapeutics, Inc.

Collaborators

This study is currently undergoing a sponsor transition from Forma to Novo Nordisk. Sponsor field will be updated once the transition is complete.

Investigators

  • Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2021

Primary Completion (Actual)

February 6, 2026

Study Completion (Estimated)

March 19, 2027

Study Registration Dates

First Submitted

November 5, 2020

First Submitted That Met QC Criteria

November 5, 2020

First Posted (Actual)

November 12, 2020

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4202-HEM-301

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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