Sickle Cell DiseasePhase 3HIBISCUSNCT04624659
A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)
A Phase 3 study testing Etavopivat Tablets Low dose, Etavopivat Tablets High dose and Etavopivat Tablets in people with Sickle Cell Disease, run by Forma Therapeutics, Inc. at 142 sites in 17 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Etavopivat Tablets Low dose, Etavopivat Tablets High dose and Etavopivat Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 450 participants
- Where
- 142 sitesin 17 countries
- Study dates
- 29 Jan 2021to 19 Mar 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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)
Trial locations and contacts
142 sites in 17 countries.
142 sites in 17 countries
United States63 sites
Cornerstone Research Institute
Altamonte Springs, Florida, 32701
Emory University School of Medicine
Atlanta, Georgia, 30303
Sonar Clinical Research
Atlanta, Georgia, 30315
Children's Healthcare of Atlanta Investigational Medication Pharmacy
Atlanta, Georgia, 30342
Center for Blood Disorders Augusta University
Augusta, Georgia, 30912
University Of Maryland School of Medicine
Baltimore, Maryland, 21201
Univ of Alabama Birmingham
Birmingham, Alabama, 35233
Massachusetts General Hospital_Boston
Boston, Massachusetts, 02114
Boston Medical Center
Boston, Massachusetts, 02118
NYC Health+Hospitals
Brooklyn, New York, 11203
[Legal] The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Medical University of South Carolina
Charleston, South Carolina, 29425
Levine Cancer Institute
Charlotte, North Carolina, 28204
University of Illinois at Chicago
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45219
[Legal] Children's Hospital Medical Center dba Cincinnati Children's
Cincinnati, Ohio, 45229
The Ohio State University Medical Center
Columbus, Ohio, 43203
iResearch Atlanta, LLC
Decatur, Georgia, 30030
[Legal] Dr. Vince Clinical Research, LLC and Dr. Vince Clinical Research, P.A.
Detroit, Michigan, 48201
Karmanos Cancer Institute
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
University of Connecticut
Farmington, Connecticut, 06030
University of Florida
Gainesville, Florida, 32610
East Carolina University
Greenville, North Carolina, 27858
Prisma Health-Upstate
Greenville, South Carolina, 29605
Foundation for Sickle Cell Disease Research
Hollywood, Florida, 33023
[Legal] Baylor College of Medicine
Houston, Texas, 77030
UT Health University of Texas
Houston, Texas, 77030
Queens Hospital Center
Jamaica, New York, 11432-1121
[Legal] Woodland International Research Group, LLC
Little Rock, Arkansas, 72211
[Legal] Collaborative Neuroscience Network, LLC
Long Beach, California, 90806
Methodist University Hospital
Memphis, Tennessee, 38104
[Legal] St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University Of Miami
Miami, Florida, 33136
Advanced Pharma CR
Miami, Florida, 33147
Versiti Blood Center of Wisconsin
Milwaukee, Wisconsin, 53226
Yale University
New Haven, Connecticut, 06519
North Shore Long Island Jewish Medical Center
New Hyde Park, New York, 11040
Children's Hosp-New Orleans
New Orleans, Louisiana, 70118
Columbia University Medical Center_New York
New York, New York, 10032
Weill Cornell Med Coll-NYPH
New York, New York, 10065
Neuro-Behavioral Clinical Research
North Canton, Ohio, 44720
Pacific Research Partners
Oakland, California, 94607
UCSF Oakland Benioff ChildHosp
Oakland, California, 94609
Jimmy Everest Cancer Hematology & Oncology
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center
Omaha, Nebraska, 68198-2168
University Of California Irvine
Orange, California, 92868
Arnold Palmer Children's Hospital
Orlando, Florida, 32806
Children's Hosptl Philadelphia
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Phoenix Children's Hsptl
Phoenix, Arizona, 85016
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213-4306
Rhode Island Hospital
Providence, Rhode Island, 02903
Virginia Commonwealth University
Richmond, Virginia, 23298
UC Davis Medical Center
Sacramento, California, 95817
Washington University School of Medicine_St. Louis
St Louis, Missouri, 63110
Mary Bridge Children's Health
Tacoma, Washington, 98405
Jacobi Medical Center
The Bronx, New York, 10461
Montefiore Medical Center
The Bronx, New York, 10467
Lynn Institute of Tulsa
Tulsa, Oklahoma, 74135
Children's National Health Hospital
Washington D.C., District of Columbia, 20010
Howard University
Washington D.C., District of Columbia, 20060
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
Spain10 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, 15006
Hospital Germans Trias i Pujol
Badalona, 8916
Hospital Universitario de Cruces
Barakaldo, 48903
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Sant Joan de Déu
Barcelona, 8950
Hospital Gregorio Marañón
Madrid, 28009
Hospital Ramón y Cajal
Madrid, 28034
Hospital Clínico San Carlos
Madrid, 28040
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen del Rocío
Seville, 41013
Turkey (Türkiye)7 sites
Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji
Adana, 1130
Başkent Üniversitesi Adana Dr. Turgut Noyan Uygulama ve Araştırma Merkezi
Adana, 1240
Adana City Training and Research Hospital
Adana, 4522
Hacettepe Üniversitesi Hastanesi- Hematoloji
Ankara, 6230
Ege Üniversitesi Tip Fakultesi Hastanesi - Nefroloji
Izmir, 35040
Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji
Mersin, 33110
VM Medical Park Mersin Hastanesi- Kardiyoloji
Mersin, 33200
United Kingdom7 sites
Leicester Royal Infirmary - Haemostasis & Thrombosis Unit
Leicester, LE1 5WW
University Hospital Lewisham, Lewisham and Greenwich NHS Trust
London, SE13 6LH
Guys and St Thomas NHS Foundation Trust / Evelina Childrens Hospital
London, SE18 3RA
Kings College Hospital - Haematology
London, SE5 9RS
Hammersmith Hospital - London
London, W2 1NY
Churchill Hospital
Oxford, OX3 7LE
Royal Hallamshire Hospital
Sheffield, S11 8RN
Egypt6 sites
[Legal] Alexandria Clinical Research LLC
Alexandria, 0
[Legal] Alexandria Clinical Research LLC
Alexandria, 21131
Cairo University
Cairo, 111111
Ain Shams University Hospital
Cairo, 1181
Al Kasr AL Aini Hospital
Cairo, 11956
Sydnawy University Hospital
Zagazig, 44519
France6 sites
Ap-Hp-Hopital Henri Mondor
Créteil, 94010
Hospices Civils de Lyon-Hopital Edouard Herriot
Lyon, 69437
Centre Hospitalier Universitaire de Montpellier-Hopital Saint-Eloi
Montpellier, 34295
GHR Mulhouse Sud-Alsace
Mulhouse, 68100
Ap-Hp-Hopital Robert Debre
Paris, 75019
Saint-Denis Hospital Center
Saint-Denis, 93200
Germany6 sites
Charité - Campus Virchow-Klinikum - Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie
Berlin, 13353
Universitätsklinikum Frankfurt
Frankfurt am Main, 60596
Universitätsklinikum Freiburg-Zentrum für Kinder- und Jugendmedizin
Freiburg im Breisgau, 79106
Universitätsklinikum Hamburg-Eppendorf - University Medical Center Hamburg-Eppendorf
Hamburg, 20246
Uniklinik Heidelberg - Klinik für Pädiatrische Onkologie, Hämatologie, Immunologie und Pneumologie
Heidelberg, 69120
Universitätsklinikum Regensburg
Regensburg, 93053
Italy6 sites
Azienda Ospedaliero Universitaria Policlinico G. Rodolico - San Marco
Catania, 95123
Azienda Ospedaliera Universitaria San Luigi Gonzaga - S.C.D.O. Microcitemie e malattie rare ematologiche
Orbassano, 10043
Azienda Ospedale Universita Padova
Padova, 35128
ARNAS Ospedali Civico Di Cristina Benfratelli - Presidio Ospedaliero "Civio e Benfratelli"
Palermo, 90127
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche Fondazione IRCCS Policlinico San Matteo
Pavia, PV, 27100
Ospedale Pediatrico Bambino Ges
Roma, 00165
India5 sites
Victoria Hospital, Bangalore
Bangalore, 560002
Srirama Chandra Bhanj Medical College & Hospital (S.C.B Medical College)
Cutack, 753007
Yashoda Hospital
Hyderabad, Telangana, 500084
K.J Somaiya Hospital and Research Centre
Mumbai, Maharashtra, 400022
All India Institute of Medical Sciences (AIIMS)
New Delhi, 110029
Nigeria5 sites
University of Abuja Teaching Hospital, Gwagwalada, Abuja
Abuja, 228
Barau Dikko Teaching Hospital, Kaduna
Kaduna, 800212
Aminu Kano Teaching Hospital (AKTH)
Kano, 3452
Lagos University Teaching Hospital, Lagos
Lagos, 102215
University of Nigeria Teaching Hospital (UNTH)
Lagos, 102215
Canada4 sites
CHU Sainte-Justine Mother and Child University Hospital
Montreal, Quebec, H3T 1C5
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
University Health Network - Toronto General Hospital
Toronto, Ontario, M5G 2C4
Providence Hematolgy
Vancouver, British Columbia, V6E 1M7
Greece4 sites
Gen Hosp Athens Ippokrateio,B' Uni Clinic Internal Medicine
Athens, 115 27
General Hospital Of Larissa Koutlibaneio And Triantafylleio - Thalassemia and SCD Unit
Larissa, 41221
General University Hospital of Patras
Pátrai, Larissa, 265 04
'Ippokrateio' General Hospital of Thessaloniki
Thessaloniki, 54642
Kenya4 sites
Kombewa Clinical Research Centre
Kisumu, 1932
KEMRI Kondele Children Hospital, Kisumu
Kisumu, 40100
KEMRI CRDR Siaya Clinical Research Annex, Country Referral Hospital
Kisumu, 40600
Gertrude's Children's Hospital
Nairobi, 100
Lebanon3 sites
Master Centre for Lebanon
Amman, 11844
American University of Beirut Medical center
Beirut, 11-0236
Hospital Nini
Tripoli, 113-6044
Saudi Arabia3 sites
King Fahad Specialist Hospital-Dammam
Dammam, 32253
Prince Mohammad Bin Naser Hospital
Jizan, 82943
King Khaled University Hospital,King Saud Univ. Med. City
Riyadh, 12372 6864
Ghana2 sites
Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital (KBTH)
Accra, 0
Kintampo Health Research Centre (KHRC)
Kintampo, Bono East, 27WF+98M
Oman1 site
Sultan Qaboos University Hospital
Muscat, Sultanet of Oman/Muscat/Al Khoud, 123
About this study
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).
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Etavopivat Tablets Low dose, Etavopivat Tablets High dose, Placebo Tablets, Etavopivat Tablets
- 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
- Medical subject headings
- Anemia, Sickle Cell, Anemia, Hemolysis, Vaso-Occlusive Crises, Anemia, Hemolytic, Hematologic Diseases, Hemoglobinopathies, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Etavopivat Tablets Low doseDrug
Also called FT-4202
200 mg once daily
Etavopivat Tablets High doseDrug
Also called FT-4202
400 mg once daily
Placebo TabletsDrug
Also called placebo
Placebo once daily
Etavopivat TabletsDrug
Also called FT-4202
Selected dose once daily
| Study group | Role | What they receive |
|---|---|---|
| Double blind etavopivat Low Dose | Experimental | Double blind etavopivat Low Dose Receives: Drug: Etavopivat Tablets Low dose |
| Double blind etavopivat High Dose | Experimental | Double blind etavopivat High Dose Receives: Drug: Etavopivat Tablets High dose |
| Double blind placebo | Experimental | Double blind placebo Receives: Drug: Placebo Tablets |
| Open label etavopivat | Experimental | Open label etavopivat Receives: Drug: Etavopivat Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemoglobin response rate
Hemoglobin response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period
Measured: 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
Measured: 52 Weeks
Secondary outcomes (6)
Hemoglobin
Change from baseline in hemoglobin at Week 52 during the blinded treatment period
Measured: 52 Weeks
Absolute reticulocyte count
Change in absolute reticulocyte count from baseline at Week 24 during the blinded treatment period
Measured: 24 Weeks
Indirect bilirubin
Change in unconjugated bilirubin from baseline at Week 24 during the blinded treatment period
Measured: 24 Weeks
Lactate dehydrogenase
Change in lactate dehydrogenase from baseline at Week 24 during the blinded treatment period
Measured: 24 Weeks
Vaso-occlusive crisis
Time to first vaso-occlusive crisis during the blinded treatment period
Measured: 52 Weeks
Fatigue
Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale from baseline in adult patients at Week 52 during the blinded treatment period
Measured: 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2020
- Study start29 Jan 2021
- Primary completion6 Feb 2026
- Study completion19 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Forma Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- This study is currently undergoing a sponsor transition from Forma to Novo Nordisk. Sponsor field will be updated once the transition is complete.
- Responsible party
- Sponsor
- Investigators
- Clinical Transparency (dept. 2834), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04624659
- Sponsor's protocol ID
- 4202-HEM-301
- Acronym
- HIBISCUS
- Status last verified
- Mar 2026
- First submitted
- 5 Nov 2020
- Last updated
- 6 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 37254256Forsyth 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.
PubMed 35019238
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04624659
- Acronym / sponsor ID
- HIBISCUS / 4202-HEM-301
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, Sickle Cell, Anemia, Sickle Cell Anemia, Hemolytic, Hemoglobin, Vaso-occlusive Crisis, Sickle Cell Crisis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Forma Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- This study is currently undergoing a sponsor transition from Forma to Novo Nordisk. Sponsor field will be updated once the transition is complete.
- Study start
- 29 Jan 2021 (actual)
- Primary completion
- 6 Feb 2026 (actual)
- Study completion
- 19 Mar 2027 (estimated)
- First posted
- 12 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Double blind etavopivat Low Dose | Experimental | Drug: Etavopivat Tablets Low doseDouble blind etavopivat Low Dose |
| Double blind etavopivat High Dose | Experimental | Drug: Etavopivat Tablets High doseDouble blind etavopivat High Dose |
| Double blind placebo | Experimental | Drug: Placebo TabletsDouble blind placebo |
| Open label etavopivat | Experimental | Drug: Etavopivat TabletsOpen label etavopivat |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (22 listed)
- More than 15 vaso-occlusive crises within the past 12 months
- Female who is breastfeeding or pregnant
- Hepatic dysfunction characterized by:
- Known HIV positivity
- Active hepatitis B or hepatitis C infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Etavopivat Tablets Low doseAlso: FT-4202200 mg once daily | Drug | Double blind etavopivat Low Dose |
| Etavopivat Tablets High doseAlso: FT-4202400 mg once daily | Drug | Double blind etavopivat High Dose |
| Placebo TabletsAlso: placeboPlacebo once daily | Drug | Double blind placebo |
| Etavopivat TabletsAlso: FT-4202Selected dose once daily | Drug | Open label etavopivat |
Primary outcome
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
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
6 secondary outcomes
Hemoglobin
Time frame: 52 Weeks
Absolute reticulocyte count
Time frame: 24 Weeks
Indirect bilirubin
Time frame: 24 Weeks
Lactate dehydrogenase
Time frame: 24 Weeks
Vaso-occlusive crisis
Time frame: 52 Weeks
Fatigue
Time frame: 52 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
- Derived from this study: PubMed 37254256Obadina 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.
- Derived from this study: PubMed 35019238Forsyth 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.
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Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Transparency (dept. 2834) study director
Novo Nordisk A/S
142 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Etavopivat Tablets Low dose, Etavopivat Tablets High dose and Etavopivat Tablets in people with Sickle Cell Disease, run by Forma Therapeutics, Inc. at 142 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 142 sites in United States, Spain, Turkey (Türkiye), United Kingdom, Egypt and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemoglobin response rate (time frame: 24 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04624659, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.