A Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease
Hibiscus 2
A Global Phase 3, Randomised, Double-blind and Placebo-controlled Study Evaluating the Efficacy and Safety of Etavopivat in Adolescents and Adults With Sickle Cell Disease
3 other identifiers
interventional
408
21 countries
172
Brief Summary
This study is conducted to confirm whether etavopivat works well at reducing the number of Vaso-occlusive crisis VOCs (sickle cell pain crises) caused by obstructions in blood vessels in adults and adolescents living with sickle cell disease. The study will also evaluate how well etavopivat can reduce the damage to different organs, improve your exercise tolerance and reduce fatigue in people with sickle cell disease.The participants will either get etavopivat or placebo. Which treatment the participants will get is decided by chance. Etavopivat is a new medicine and is currently being tested in other studies in addition to this one. The study will last for about 2 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Feb 2025
Typical duration for phase_3
172 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2024
CompletedFirst Posted
Study publicly available on registry
September 25, 2024
CompletedStudy Start
First participant enrolled
February 17, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 27, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 12, 2029
April 24, 2026
April 1, 2026
2.5 years
September 23, 2024
April 23, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact
Measured as Count of events.
Baseline (week 0) to week 52
Secondary Outcomes (10)
Change in Haemoglobin (Hb) greater than 1 grams per decilitre (g/dL)
Baseline (week 0) to week 24
Time to onset of first adjudicated Vaso-occlusive crisis (VOC)
Baseline (week 0) to week 52
Change in standardised T-score on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a Scale
Baseline (week 0) to week 52
Change in haemoglobin (Hb)
Baseline (week 0) to week 52
Change in lactate dehydrogenase (LDH)
Baseline (week 0) to week 52
- +5 more secondary outcomes
Study Arms (2)
Etavopivat
EXPERIMENTALParticipants will be randomised to receive oral dose of Etavopivat.
Placebo
PLACEBO COMPARATORParticipants will be randomised to receive oral dose of placebo.
Interventions
Eligibility Criteria
You may qualify if:
- Male or female.
- Age 12 years or above at the time of signing the informed consent.
- Confirmed diagnosis of sickle cell disease: Documentation of sickle cell disease (SCD) genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing or screening test results from central laboratory. Molecular genotyping is not required. SCD genotype may be determined from the results of haemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC) or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening.
- Have 1-15 episodes of documented vaso occlusive crises (VOC) within the 12 months prior to screening. Documentation must exist in the participant's medical record prior to randomisation. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.
- Hb greater than or equal to (≥) 5.0 and less than or equal to (≤) 10.0 g/dL (greater than or equal to (≥) 50 and less than or equal to (≤) 100 g/L) at screening.
You may not qualify if:
- More than 15 VOCs within the past 12 months prior to screening documented in the participant's medical record. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.
- Use of voxelotor or similar agent within 28 days prior to starting study treatment or anticipated need for this agent during the study.
- Use of a selectin antagonist (e.g., crizanlizumab, monoclonal antibody or small molecule) within 28 days or 5 half-lives (whichever is longer) prior to starting study treatment or anticipated need for such agents during the study.
- Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or greater than or equal to 6 transfusion events in the previous 12 months (i.e., an average of 1 transfusion event every 60 days).
- Participants who have received an RBC transfusion for any reason within 60 days of the screening period or 60 days of the randomisation day are only eligible if HbA (adult haemoglobin) less than 10% by Hb electrophoresis is documented prior to starting study treatment.
- Receiving or use of concomitant medications that are strong inducers of CYP3A4 (cytochrome p450 3a4) within 2 weeks of starting study treatment or anticipated need for such agents during the study.
- Use of erythropoietin or other haematopoietic 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 (e.g., haematopoietic cell transplant, gene modification therapy).
- Hepatic dysfunction characterized by:
- Alanine aminotransferase (ALT) greater than 4.0 × upper limit of normal (ULN) or
- Direct bilirubin greater than 3.0 × ULN.
- Participants who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended.
- Severe renal dysfunction (estimated glomerular filtration rate \[eGFR\] at screening, calculated by the central laboratory greater than 30 mL/min/1.73 m\^ 2) or on chronic dialysis.
- Travelled distance on standardized 6MWT below 100m at screening.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novo Nordisk A/Slead
Study Sites (172)
Uni of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Univer South Alabama Ped/Onc
Mobile, Alabama, 36604, United States
Phoenix Children's Hsptl
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
Children's Hospital Los Angeles - Endocrinology
Los Angeles, California, 90027, United States
UCLA Health
Los Angeles, California, 90095, United States
Valley Children's Hospital
Madera, California, 93636, United States
University Of California Irvine
Orange, California, 92868, United States
Stanford University_Palo Alto
Palo Alto, California, 94304, United States
Harbor-UCLA Medical Center
Torrance, California, 90502, United States
Clinical and Transl Res Center
Aurora, Colorado, 80045, United States
Nemours/AI duPont Hosp-Chld
Wilmington, Delaware, 19803, United States
Childrens National Medical Ctr
Washington D.C., District of Columbia, 20010, United States
MedStar Hlth Res Institute
Washington D.C., District of Columbia, 20010, United States
Memorial Healthcare
Hollywood, Florida, 33021, United States
Children's Healthcare Atlanta
Atlanta, Georgia, 30329, United States
Childrens Hospital of Chicago
Chicago, Illinois, 60611, United States
Univer Of Illinois at Chicago
Chicago, Illinois, 60612, United States
Children's Hosp-New Orleans
New Orleans, Louisiana, 70118, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Boston Medical Center
Boston, Massachusetts, 02118-2393, United States
Henry Ford Hospital_Detroit
Detroit, Michigan, 48202, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Washington University-St.Louis
St Louis, Missouri, 63110, United States
Children's Nebraska
Omaha, Nebraska, 68114, United States
Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
Newark Beth Israel MC
Newark, New Jersey, 07112-2027, United States
NYC Health+Hospitals
Brooklyn, New York, 11203, United States
Interfaith Medical Center
Brooklyn, New York, 11238, United States
Northwell Health
Mount Kisco, New York, 10549, United States
Cohen Children's Medical Ctr
Queens, New York, 11040, United States
Jacobi Medical Center
The Bronx, New York, 10461, United States
Montefiore Medical Ctr
The Bronx, New York, 10467, United States
Duke Comprehen Sickle Cell
Durham, North Carolina, 27710, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
East Carolina Univ-Greenville
Greenville, North Carolina, 27834, United States
Atrium Health-Wake Forest Bapt
Winston-Salem, North Carolina, 27157, United States
Univ Hosp Cleveland Med Ctr
Cleveland, Ohio, 44106, United States
Ohio State Univ Wexner Med Ctr
Columbus, Ohio, 43203, United States
Univ of OK Health Sciences Ctr
Oklahoma City, Oklahoma, 73104, United States
Children's Hosptl Philadelphia
Philadelphia, Pennsylvania, 19104, United States
St Christopher Hosp for Child
Philadelphia, Pennsylvania, 19134, United States
University of Tennessee Health Science Center
Memphis, Tennessee, 38104, United States
St. Jude Children's Res Hosp
Memphis, Tennessee, 38105, United States
UT Health University of Texas
Houston, Texas, 77030, United States
Inova Health System
Fairfax, Virginia, 22031, United States
Children's Hsptl Of The Kings
Norfolk, Virginia, 23507, United States
Virginia Comm Univ Medical Ctr
Richmond, Virginia, 23298, United States
Mary Bridge Children's Health
Tacoma, Washington, 98405, United States
Mary Bridge Children's Health
Tacoma, Washington, 98405, United States
Royal Prince Alfred Hospital - Department of Haematology
Camperdown, New South Wales, 2050, Australia
Prince of Wales Hospital - Department of Haematology
Randwick, New South Wales, 2031, Australia
Monash Medical Centre - Haematology Department
Clayton, Victoria, 3168, Australia
Fiona Stanley Hospital - Haemophilia and Haemostasis Centre
Murdoch, Western Australia, 6150, Australia
CHU Saint-Pierre - UMC Sint-Pieter
Brussels, 1000, Belgium
CHU - UVC Brugmann
Brussels, 1020, Belgium
HUB - Hôpital Erasme
Brussels, 1070, Belgium
UZ Antwerpen - UZA - Haematology
Edegem, 2650, Belgium
UZ Antwerpen - UZA - Kinderhemato-Oncologie
Edegem, 2650, Belgium
UZ Leuven - Kindergeneeskunde
Leuven, 3000, Belgium
MultiHemo - Grupo Oncoclínicas
Recife, Pernambuco, 50070-460, Brazil
MultiHemo - Grupo Oncoclínicas
Recife, Pernambuco, 52070-460, Brazil
Hemocentro UNICAMP
Distrito de Barão Geraldo - Campinas, São Paulo, 13083-878, Brazil
HC da FMUSP Hospital das Clínicas São Paulo
São Paulo, São Paulo, 05403-010, Brazil
HC da FMUSP Hospital das Clínicas São Paulo
São Paulo, São Paulo, 05403-010, Brazil
Fundação Hemocentro de Ribeirão Preto
Ribeirão Preto, São, 14051-140, Brazil
Hemorio-Fundarj
Rio de Janeiro, 20211-030, Brazil
Hospital Samaritano Higienópolis - Instituto de Conhecimento Ensino e Pesquisa (ICEP)
São Paulo, 01229-001, Brazil
Foothills Med Ctr-Univ Calgary
Calgary, Alberta, T2N 2T9, Canada
Stollery Children's Hospital
Edmonton, Alberta, T6G 2B7, Canada
University of Alberta_Edmonton
Edmonton, Alberta, T6G 2B7, Canada
BC Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
St Pauls Hospital
Vancouver, British Columbia, V6Z 2A5, Canada
LHSC - Victoria Hospital
London, Ontario, N6A5W9, Canada
Scarborough Health Network Research Institute (SHNRI)
Scarborough Village, Ontario, M1E 4B9, Canada
UHN-Toronto General Hospital
Toronto, Ontario, M5G 2C4, Canada
University of Toronto
Toronto, Ontario, M5G1X8, Canada
CHUM-Hosp de Univ Montreal
Montreal, Quebec, H2X 0C1, Canada
Montreal Children's Hospital
Montreal, Quebec, H4A 3J1, Canada
Hospital Pablo Tobon Uribe
Medellín, Antioquia, 50034, Colombia
Clinica de la Costa
Barranquilla, Atlántico, 80020, Colombia
Sociedad de Oncología y Hematología del Cesar SAS (SOHEC)
Valledupar, Cesar Department, 200001, Colombia
Clínica IMAT Oncomedica Auna S.A.S.
Montería, Departamento de Córdoba, 230002, Colombia
Centro de investigaciones clínicas, fudación valle del lili
Cali, Valle del Cauca Department, 760032, Colombia
Sociedad de Oncología y Hematología del Cesar SAS (SOHEC)
Antioquia, 4006, Colombia
Centro de investigaciones clínicas, fudación valle del lili
Cali, 760032, Colombia
Clínica IMAT Oncomedica Auna S.A.S.
Montería, 230002, Colombia
Ap-Hp-Hopital Avicenne
Bobigny, 93000, France
Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin
Bordeaux, 33000, France
Ap-Hp-Hopital Henri Mondor
Créteil, 94000, France
Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon
Grenoble, 38043, France
Hospices Civils de Lyon-Hopital Edouard Herriot
Lyon, 69437, France
AP-HP-HOPITAL NECKER_Service d'hématologie
Paris, 75015, France
Ap-Hp-Hopital Robert Debre
Paris, 75019, France
Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
Rouen, 76031, France
Kintampo Health Research Centre (KHRC)
Kintampo, Bono East, 27WF+98M, Ghana
Navrongo Health Research Centre
Navrongo, Upper East Region, UB-03821, Ghana
Agogo Presbyterian Hospital, Ghana
Agogo, 0000, Ghana
"Laiko" General Hospital of Athens
Athens, 115 26, Greece
Childrens' Hospital of Athens "Agia Sofia"
Athens, 115 27, Greece
Hippokration Hospital
Athens, 11527, Greece
Hippokration Hospital
Athens, 11527, Greece
University General Hospital Of Ioannina
Ioannina, 45500, Greece
University General Hospital Of Ioannina
Ioannina, 45500, Greece
"AHEPA" University General Hospital of Thessaloniki
Thessaloniki, 546 36, Greece
"AHEPA" University General Hospital of Thessaloniki
Thessaloniki, 546 36, Greece
Gauhati Medical College and Hospital
Guwahati, Assam, 781032, India
All India Institute of Medical Sciences (AIIMS), Raipur
Raipur, Chhattisgarh, 492099, India
Zydus Medical College & Hospital
Dohad, Gujarat, 389151, India
Nirmal Hospital Pvt. Ltd.
Surat, Gujarat, 395002, India
SSG Hospital, Baroda
Vadodara, Gujarat, 390001, India
HOCC Haemato Oncology Care Centre
Vadodara, Gujarat, 390020, India
JSS Hospital, Mysore
Mysuru, Karnataka, 570004, India
Government Medical College, Kozhikode
Kozhikode, Kerala, 673008, India
Government Medical College, Kozhikode
Kozhikode, Kerala, 673008, India
Arihant Multispeciality Hospital
Nagpur, Maharashtra, 440026, India
IMS and SUM Hospital
Bhubaneswar, Odisha, 751003, India
RNT Medical College
Udaipur, Rajasthan, 313001, India
NIZAM'S Institute of Medical Sciences
Hyderabad, Telangana, 500082, India
Post Graduate Institute of Child Health
Noida, Uttar Pradesh, 201303, India
All India Institute of Medical Sciences_New Dehli
New Delhi, 110029, India
Azienda Ospedaliera Universitaria San Luigi Gonzaga - S.C.D.O. Microcitemie e malattie rare ematologiche
Orbassano, Torino, 10043, Italy
Azienda Ospedaliera Universitaria San Luigi Gonzaga
Orbassano, Torino, 10043, Italy
Azienda Ospedaliera Universitaria Integrata Verona Policlinico GB Rossi - Borgo Roma - Centro Ricerche Cliniche Di Verona S.r.l.
Verona, Veneto, 37134, Italy
ASST Civili di Brescia
Brescia, 25123, Italy
ARNAS Garibaldi Catania - Presidio Ospedaliero Garibaldi-Centro
Catania, 95123, Italy
Azienda Ospedaliero Universitaria Di Modena - UOC Pediatria ad indirizzo Oncoematologico
Modena, 41100, Italy
Fondazione IRCCS San Gerardo dei Tintori
Monza, 20900, Italy
A.O.U. Università Studi della Campania "Luigi Vanvitelli"
Naples, 80138, Italy
Azienda Ospedale Universita Padova
Padova, 35128, Italy
Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
Palermo, 90146, Italy
Gertrude's Children's Hospital
Nairobi, Nairobi County, 00509, Kenya
KEMRI CRDR Siaya Clinical Research Annex, Country Referral Hospital
Siaya, Siaya County, 40600, Kenya
International Cancer Institute (ICI)
Eldoret, Uasin Gishu County, 8088-30100, Kenya
Ahero Clinical Trials Unit
Kisumu, 40101, Kenya
American University of Beirut Medical Centre
Hamra, 11-0236, Lebanon
Hospital Nini
Tripoli, 1434, Lebanon
AmsterdamUMC VUMC - Hematologie
Amsterdam, 1081 HV, Netherlands
Erasmus MC
Rotterdam, 3015 GD, Netherlands
HagaZiekenhuis
The Hague, 2545AA, Netherlands
UMC Utrecht, Van Creveldkliniek
Utrecht, 3584 CX, Netherlands
University of Nigeria Teaching Hospital (UNTH)
Ituku-Ozalla, Enugu State, 400001, Nigeria
Centre of Excellence for Sickle Cell Disease Research and Training, University of Abuja (CESRTA)
Abuja, Federal Capital Territory (fct), 90410, Nigeria
University College Hospital Paediatric Haematology and Oncology Unit, Ibadan
Ibadan, Oyo State, 0000, Nigeria
Lagos University Teaching Hospital, Lagos
Lagos, 102215, Nigeria
Sultan Qaboos University Hospital
Muscat, Sultanet of Oman/Muscat/Al Khoud, 123, Oman
The Royal Hospital
Muscat, 111, Oman
King Abdulaziz Hospital-Al Ahsa-National Guard
Al Ahsa, 36428, Saudi Arabia
National Guard Hospital Dammam
Dhahran, 34232, Saudi Arabia
King Faisal Specialist Hospital & Research Centre, Riyadh
Riyadh, 12713, Saudi Arabia
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Hospital Gregorio Marañón
Madrid, 28009, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Universitario Virgen del Rocío
Seville, 41013, Spain
Acıbadem Adana Hastanesi-Hematoloji
Adana, 01130, Turkey (Türkiye)
Başkent Üniversitesi Adana-Hematoloji
Adana, 01250, Turkey (Türkiye)
Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji
Adana, 01250, Turkey (Türkiye)
Hacettepe University Hematology
Ankara, 06230, Turkey (Türkiye)
Hacettepe Üniversitesi Hastanesi- Hematoloji
Ankara, 06230, Turkey (Türkiye)
Mersin University Medical Faculty Pediatric Hematology
Mersin, 33110, Turkey (Türkiye)
Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji
Mersin, 33110, Turkey (Türkiye)
VM Medical Park Mersin Hastanesi- Kardiyoloji
Mersin, 33200, Turkey (Türkiye)
Makerere University College of Health Sciences (MakCHS)
Kampala, Central Region, 00000, Uganda
Joint Clinical Research Centre (JCRC)
Kampala, Central Region (Wakiso District), 00000, Uganda
Jinja Regional Referral Hospital
Jinja, Eastern Region, 0000, Uganda
Addenbrooke's Hospital - Haemophilia and Thrombophilia
Cambridge, CB2 0QQ, United Kingdom
Whittington Hospital
London, N19 5NF, United Kingdom
Guy's Hospital - Haematology
London, SE1 9RT, United Kingdom
King's College Hospital - Paediatric Research
London, SE5 9RS, United Kingdom
Kings College Hospital - Haematology
London, SE5 9RS, United Kingdom
Imperial College London
London, W12 0NN, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Transparency (dept. 2834)
Novo Nordisk A/S
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Sponsor staff involved in the clinical trial is masked according to company standard procedures.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2024
First Posted
September 25, 2024
Study Start
February 17, 2025
Primary Completion (Estimated)
August 27, 2027
Study Completion (Estimated)
March 12, 2029
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com