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

NCT04624659 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 4202-HEM-301
• Study Type: interventional
• Target: 450
• Locations: 17 countries
• Sites: 142

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).

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; Sickle Cell; Anemia; Sickle Cell Anemia; Hemolytic; Hemoglobin; Vaso-occlusive Crisis; Sickle Cell Crisis; Congenital Anemia; Hemolytic Anemia; Hematologic Disease; Hemoglobinopathies; Genetic Disease; Inborn Disease; Sickle Cell Trait; Pyruvate Kinase

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• Hemoglobin

  52 Weeks

• Absolute reticulocyte count

  24 Weeks

• Indirect bilirubin

  24 Weeks

• Lactate dehydrogenase

  24 Weeks

• Vaso-occlusive crisis

  52 Weeks

Study Arms (4)

Double blind etavopivat Low Dose

EXPERIMENTAL

Double blind etavopivat Low Dose

Drug: Etavopivat Tablets Low dose

Double blind etavopivat High Dose

EXPERIMENTAL

Double blind etavopivat High Dose

Drug: Etavopivat Tablets High dose

Double blind placebo

EXPERIMENTAL

Double blind placebo

Drug: Placebo Tablets

Open label etavopivat

EXPERIMENTAL

Open label etavopivat

Drug: Etavopivat Tablets

Interventions

Etavopivat Tablets Low dose DRUG

200 mg once daily

Also known as: FT-4202

Double blind etavopivat Low Dose

Etavopivat Tablets High dose DRUG

400 mg once daily

Also known as: FT-4202

Double blind etavopivat High Dose

Placebo Tablets DRUG

Placebo once daily

Also known as: placebo

Double blind placebo

Etavopivat Tablets DRUG

Selected dose once daily

Also known as: FT-4202

Open label etavopivat

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Forma Therapeutics, Inc.: lead
• This study is currently undergoing a sponsor transition from Forma to Novo Nordisk. Sponsor field will be updated once the transition is complete.: collaborator

Study Sites (142)

Univ of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hsptl

Phoenix, Arizona, 85016, United States

Location

[Legal] Woodland International Research Group, LLC

Little Rock, Arkansas, 72211, United States

Location

[Legal] Collaborative Neuroscience Network, LLC

Long Beach, California, 90806, United States

Location

Pacific Research Partners

Oakland, California, 94607, United States

Location

UCSF Oakland Benioff ChildHosp

Oakland, California, 94609, United States

Location

University Of California Irvine

Orange, California, 92868, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Connecticut

Farmington, Connecticut, 06030, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Howard University

Washington D.C., District of Columbia, 20060, United States

Location

Cornerstone Research Institute

Altamonte Springs, Florida, 32701, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Foundation for Sickle Cell Disease Research

Hollywood, Florida, 33023, United States

Location

University Of Miami

Miami, Florida, 33136, United States

Location

Advanced Pharma CR

Miami, Florida, 33147, United States

Location

Arnold Palmer Children's Hospital

Orlando, Florida, 32806, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30303, United States

Location

Sonar Clinical Research

Atlanta, Georgia, 30315, United States

Location

Children's Healthcare of Atlanta Investigational Medication Pharmacy

Atlanta, Georgia, 30342, United States

Location

Center for Blood Disorders Augusta University

Augusta, Georgia, 30912, United States

Location

iResearch Atlanta, LLC

Decatur, Georgia, 30030, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Children's Hosp-New Orleans

New Orleans, Louisiana, 70118, United States

Location

University Of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital_Boston

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

[Legal] Dr. Vince Clinical Research, LLC and Dr. Vince Clinical Research, P.A.

Detroit, Michigan, 48201, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine_St. Louis

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-2168, United States

Location

Children's National Health Hospital

Washington, New Jersey, 20010, United States

Location

NYC Health+Hospitals

Brooklyn, New York, 11203, United States

Location

Queens Hospital Center

Jamaica, New York, 11432-1121, United States

Location

North Shore Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Columbia University Medical Center_New York

New York, New York, 10032, United States

Location

Weill Cornell Med Coll-NYPH

New York, New York, 10065, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

[Legal] The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

[Legal] Children's Hospital Medical Center dba Cincinnati Children's

Cincinnati, Ohio, 45229, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43203, United States

Location

Neuro-Behavioral Clinical Research

North Canton, Ohio, 44720, United States

Location

Jimmy Everest Cancer Hematology & Oncology

Oklahoma City, Oklahoma, 73104, United States

Location

Lynn Institute of Tulsa

Tulsa, Oklahoma, 74135, United States

Location

Children's Hosptl Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213-4306, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Prisma Health-Upstate

Greenville, South Carolina, 29605, United States

Location

Methodist University Hospital

Memphis, Tennessee, 38104, United States

Location

[Legal] St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

[Legal] Baylor College of Medicine

Houston, Texas, 77030, United States

Location

UT Health University of Texas

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Mary Bridge Children's Health

Tacoma, Washington, 98405, United States

Location

Versiti Blood Center of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Providence Hematolgy

Vancouver, British Columbia, V6E 1M7, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

University Health Network - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

CHU Sainte-Justine Mother and Child University Hospital

Montreal, Quebec, H3T 1C5, Canada

Location

[Legal] Alexandria Clinical Research LLC

Alexandria, 0, Egypt

Location

[Legal] Alexandria Clinical Research LLC

Alexandria, 21131, Egypt

Location

Cairo University

Cairo, 111111, Egypt

Location

Ain Shams University Hospital

Cairo, 1181, Egypt

Location

Al Kasr AL Aini Hospital

Cairo, 11956, Egypt

Location

Sydnawy University Hospital

Zagazig, 44519, Egypt

Location

Ap-Hp-Hopital Henri Mondor

Créteil, 94010, France

Location

Hospices Civils de Lyon-Hopital Edouard Herriot

Lyon, 69437, France

Location

Centre Hospitalier Universitaire de Montpellier-Hopital Saint-Eloi

Montpellier, 34295, France

Location

GHR Mulhouse Sud-Alsace

Mulhouse, 68100, France

Location

Ap-Hp-Hopital Robert Debre

Paris, 75019, France

Location

Saint-Denis Hospital Center

Saint-Denis, 93200, France

Location

Charité - Campus Virchow-Klinikum - Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie

Berlin, 13353, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60596, Germany

Location

Universitätsklinikum Freiburg-Zentrum für Kinder- und Jugendmedizin

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Hamburg-Eppendorf - University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Uniklinik Heidelberg - Klinik für Pädiatrische Onkologie, Hämatologie, Immunologie und Pneumologie

Heidelberg, 69120, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital (KBTH)

Accra, 0, Ghana

Location

Kintampo Health Research Centre (KHRC), Kintampo, Ghana

Kintampo, 200, Ghana

Location

General University Hospital of Patras

Pátrai, Larissa, 265 04, Greece

Location

Gen Hosp Athens Ippokrateio,B' Uni Clinic Internal Medicine

Athens, 115 27, Greece

Location

General Hospital Of Larissa Koutlibaneio And Triantafylleio - Thalassemia and SCD Unit

Larissa, 41221, Greece

Location

'Ippokrateio' General Hospital of Thessaloniki

Thessaloniki, 54642, Greece

Location

K.J Somaiya Hospital and Research Centre

Mumbai, Maharashtra, 400022, India

Location

Yashoda Hospital

Hyderabad, Telangana, 500084, India

Location

Victoria Hospital, Bangalore

Bangalore, 560002, India

Location

Srirama Chandra Bhanj Medical College & Hospital (S.C.B Medical College)

Cutack, 753007, India

Location

All India Institute of Medical Sciences (AIIMS)

New Delhi, 110029, India

Location

Centro per lo Studio e la Cura delle Amiloidosi Sistemiche Fondazione IRCCS Policlinico San Matteo

Pavia, PV, 27100, Italy

Location

Azienda Ospedaliero Universitaria Policlinico G. Rodolico - San Marco

Catania, 95123, Italy

Location

Azienda Ospedaliera Universitaria San Luigi Gonzaga - S.C.D.O. Microcitemie e malattie rare ematologiche

Orbassano, 10043, Italy

Location

Azienda Ospedale Universita Padova

Padua, 35128, Italy

Location

ARNAS Ospedali Civico Di Cristina Benfratelli - Presidio Ospedaliero "Civio e Benfratelli"

Palermo, 90127, Italy

Location

Ospedale Pediatrico Bambino Ges

Roma, 00165, Italy

Location

Kombewa Clinical Research Centre

Kisumu, 1932, Kenya

Location

KEMRI Kondele Children Hospital, Kisumu

Kisumu, 40100, Kenya

Location

KEMRI Siaya Clinical Research Annex Siaya County Referral Hospital, Siaya

Kisumu, 40600, Kenya

Location

Gertrude's Children's Hospital, Nairobi

Nairobi, 100, Kenya

Location

Master Centre for Lebanon

Amman, 11844, Lebanon

Location

American University of Beirut Medical center

Beirut, 11-0236, Lebanon

Location

Hospital Nini

Tripoli, 113-6044, Lebanon

Location

University of Abuja Teaching Hospital, Gwagwalada, Abuja

Abuja, 228, Nigeria

Location

Barau Dikko Teaching Hospital, Kaduna

Kaduna, 800212, Nigeria

Location

Aminu Kano Teaching Hospital (AKTH)

Kano, 3452, Nigeria

Location

Lagos University Teaching Hospital, Lagos

Lagos, 102215, Nigeria

Location

University of Nigeria Teaching Hospital, Enugu

Lagos, 102215, Nigeria

Location

Sultan Qaboos University Hospital

Muscat, Sultanet of Oman/Muscat/Al Khoud, 123, Oman

Location

King Fahad Specialist Hospital-Dammam

Dammam, 32253, Saudi Arabia

Location

Prince Mohammad Bin Naser Hospital

Jizan, 82943, Saudi Arabia

Location

King Khaled University Hospital,King Saud Univ. Med. City

Riyadh, 12372 6864, Saudi Arabia

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital Germans Trias i Pujol

Badalona, 8916, Spain

Location

Hospital Universitario de Cruces

Barakaldo, 48903, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Sant Joan de Déu

Barcelona, 8950, Spain

Location

Hospital Gregorio Marañón

Madrid, 28009, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji

Adana, 1130, Turkey (Türkiye)

Location

Başkent Üniversitesi Adana Dr. Turgut Noyan Uygulama ve Araştırma Merkezi

Adana, 1240, Turkey (Türkiye)

Location

Adana City Training and Research Hospital

Adana, 4522, Turkey (Türkiye)

Location

Hacettepe Üniversitesi Hastanesi- Hematoloji

Ankara, 6230, Turkey (Türkiye)

Location

Ege Üniversitesi Tip Fakultesi Hastanesi - Nefroloji

Izmir, 35040, Turkey (Türkiye)

Location

Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji

Mersin, 33110, Turkey (Türkiye)

Location

VM Medical Park Mersin Hastanesi- Kardiyoloji

Mersin, 33200, Turkey (Türkiye)

Location

Leicester Royal Infirmary - Haemostasis & Thrombosis Unit

Leicester, LE1 5WW, United Kingdom

Location

University Hospital Lewisham, Lewisham and Greenwich NHS Trust

London, SE13 6LH, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust / Evelina Childrens Hospital

London, SE18 3RA, United Kingdom

Location

Kings College Hospital - Haematology

London, SE5 9RS, United Kingdom

Location

Hammersmith Hospital - London

London, W2 1NY, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S11 8RN, United Kingdom

Location

Related Publications (2)

• Obadina M, Wilson S, Derebail VK, Little J. Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations. Kidney360. 2023 Jul 1;4(7):997-1005. doi: 10.34067/KID.0000000000000162. Epub 2023 May 31.

  PMID: 37254256 DERIVED

• Forsyth S, Schroeder P, Geib J, Vrishabhendra L, Konstantinidis DG, LaSalvia K, Ribadeneira MD, Wu E, Kelly P, Kalfa TA. Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial. Clin Pharmacol Drug Dev. 2022 May;11(5):654-665. doi: 10.1002/cpdd.1058. Epub 2022 Jan 12.

  PMID: 35019238 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Anemia; Hemolysis; Vaso-Occlusive Crises; Anemia, Hemolytic; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Sickle Cell Trait

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 12, 2020
• Study Start: January 29, 2021
• Primary Completion: February 20, 2026
• Study Completion (Estimated): March 19, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

NG (5); CA (4); FR (6); OM (1); EG (6); IN (5); TU (7); SA (3); GH (2); GB (7); ES (10); GR (4); DE (6); IT (6); KE (4); US (63); LE (3)