A Research Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease
- Registration Number
- NCT06612268
- Lead Sponsor
- Novo Nordisk A/S
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 408
- 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.
-
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.
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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.
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Etavopivat Etavopivat Participants will be randomised to receive oral dose of Etavopivat. Placebo Placebo Participants will be randomised to receive oral dose of placebo.
- Primary Outcome Measures
Name Time Method Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact Baseline (week 0) to week 52 Measured as Count of events.
Time to onset of first adjudicated Vaso-occlusive crisis (VOC) Baseline (week 0) to week 52 Measured as time in days.
Change in distance travelled during the 6-minute walking test (6MWT) Baseline (week 0) to week 52 Measured in Meters.
Change in standardised T-score on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a Scale Baseline (week 0) to week 52 Measured in T-score.
- Secondary Outcome Measures
Name Time Method Change in haemoglobin (Hb) Baseline (week 0) to week 52 Measured in grams per decilitre (g/dL).
Change in Haemoglobin (Hb) greater than 1 grams per decilitre (g/dL) Baseline (week 0) to week 52 Measured in Count of participants.
Change in lactate dehydrogenase (LDH) Baseline (week 0) to week 52 Measured in Units per litre (U/L).
Change in absolute reticulocyte count Baseline (week 0) to week 52 Measured as Cells x10\^9/L.
Change in indirect bilirubin Baseline (week 0) to week 52 Measured in milligrams per decilitre (mg/dL).
Changes in estimated glomerular filtration rate (eGFR) Baseline (week 0) to week 52 Measured in millilitre per minute per 1.73m\^2 (mL/min/ 1.73 m\^2).
Change in albumin:creatinine ratio (ACR) Baseline (week 0) to week 52 Measured in Percent (%).
Occurrence of moderate/severe albuminuria (yes/no) Baseline (week 0) to week 52 Measured as Count of participants.
Change in N-terminal pro b-type natriuretic peptide (NT-pro-BNP) Baseline (week 0) to week 52 Measured in picograms per millilitre (pg/mL).
Proportion of participants achieving the threshold for clinically meaningful change (yes/no) in PROMIS fatigue scale 7a Baseline (week 0) to week 52 Measured as Count of participants.
Proportion of participants achieving the threshold for clinically meaningful change (yes/no) in 6MWT Baseline (week 0) to week 52 Measured as Count of participants.
Trial Locations
- Locations (155)
Ap-Hp-Hopital Henri Mondor
🇫🇷Créteil, France
UMC Utrecht, Van Creveldkliniek
🇳🇱Utrecht, Netherlands
Uni of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Univer South Alabama Ped/Onc
🇺🇸Mobile, Alabama, United States
Phoenix Children's Hsptl
🇺🇸Phoenix, Arizona, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Children's Hospital Los Angeles - Endocrinology
🇺🇸Los Angeles, California, United States
UCLA Health
🇺🇸Los Angeles, California, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
University Of California Irvine
🇺🇸Orange, California, United States
Stanford University_Palo Alto
🇺🇸Palo Alto, California, United States
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Clinical and Transl Res Center
🇺🇸Aurora, Colorado, United States
Nemours/AI duPont Hosp-Chld
🇺🇸Wilmington, Delaware, United States
Washington University-St.Louis
🇺🇸Saint Louis, Missouri, United States
Childrens National Medical Ctr
🇺🇸Washington, District of Columbia, United States
MedStar Hlth Res Institute
🇺🇸Washington, District of Columbia, United States
Memorial Healthcare
🇺🇸Hollywood, Florida, United States
Children's Healthcare Atlanta
🇺🇸Atlanta, Georgia, United States
Childrens Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Univer Of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Children's Hosp-New Orleans
🇺🇸New Orleans, Louisiana, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital_Detroit
🇺🇸Detroit, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Children's Nebraska
🇺🇸Omaha, Nebraska, United States
Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
Montefiore Medical Ctr
🇺🇸Bronx, New York, United States
NYC Health+Hospitals
🇺🇸Brooklyn, New York, United States
Interfaith Medical Center
🇺🇸Brooklyn, New York, United States
Northwell Health
🇺🇸Mount Kisco, New York, United States
Cohen Children's Medical Ctr
🇺🇸Queens, New York, United States
Duke Comprehen Sickle Cell
🇺🇸Durham, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
East Carolina Univ-Greenville
🇺🇸Greenville, North Carolina, United States
Atrium Health-Wake Forest Bapt
🇺🇸Winston-Salem, North Carolina, United States
Univ Hosp Cleveland Med Ctr
🇺🇸Cleveland, Ohio, United States
Ohio State Univ Wexner Med Ctr
🇺🇸Columbus, Ohio, United States
Univ of OK Health Sciences Ctr
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hosptl Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
St Christopher Hosp for Child
🇺🇸Philadelphia, Pennsylvania, United States
Methodist University Hospital
🇺🇸Memphis, Tennessee, United States
St. Jude Children's Res Hosp
🇺🇸Memphis, Tennessee, United States
UT Health University of Texas
🇺🇸Houston, Texas, United States
Inova Health System
🇺🇸Fairfax, Virginia, United States
Children's Hsptl Of The Kings
🇺🇸Norfolk, Virginia, United States
Virginia Comm Univ Medical Ctr
🇺🇸Richmond, Virginia, United States
Mary Bridge Children's Health
🇺🇸Tacoma, Washington, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Prince of Wales Hospital - Department of Haematology
🇦🇺Randwick, New South Wales, Australia
Fiona Stanley Hospital - Haemophilia and Haemostasis Centre
🇦🇺Murdoch, Western Australia, Australia
CHU Saint-Pierre - UMC Sint-Pieter
🇧🇪Bruxelles, Belgium
CHU - UVC Brugmann
🇧🇪Bruxelles, Belgium
Monash Health
🇦🇺Clayton, Victoria, Australia
HUB - Hôpital Erasme
🇧🇪Bruxelles, Belgium
UZ Antwerpen - UZA - Haematology
🇧🇪Edegem, Belgium
UZ Antwerpen - UZA - Kinderhemato-Oncologie
🇧🇪Edegem, Belgium
UZ Leuven - Kindergeneeskunde
🇧🇪Leuven, Belgium
Hemorio-Fundarj
🇧🇷Rio de Janeiro, Brazil
Hospital Samaritano Higienópolis - Instituto de Conhecimento Ensino e Pesquisa (ICEP)
🇧🇷São Paulo, Brazil
MultiHemo - Grupo Oncoclínicas
🇧🇷Recife, Pernambuco, Brazil
HC da FMUSP Hospital das Clínicas São Paulo
🇧🇷São Paulo, SP, Brazil
Hemocentro UNICAMP
🇧🇷Distrito De Barão Geraldo - Campinas, São Paulo, Brazil
Fundação Hemocentro de Ribeirão Preto
🇧🇷Ribeirão Preto, São, Brazil
Foothills Med Ctr-Univ Calgary
🇨🇦Calgary, Alberta, Canada
Stollery Children's Hospital
🇨🇦Edmonton, Alberta, Canada
BC Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
University of Alberta_Edmonton
🇨🇦Edmonton, Alberta, Canada
LHSC - Victoria Hospital
🇨🇦London, Ontario, Canada
UHN-Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
University of Toronto
🇨🇦Toronto, Ontario, Canada
CHUM-Hosp de Univ Montreal
🇨🇦Montreal, Quebec, Canada
Montreal Children's Hospital
🇨🇦Montreal, Quebec, Canada
Hospital Pablo Tobon Uribe
🇨🇴Medellin, Antioquia, Colombia
Clinica de la Costa
🇨🇴Barranquilla, Atlántico, Colombia
Sociedad de Oncología y Hematología del Cesar SAS (SOHEC)
🇨🇴Antioquia, Colombia
Clínica IMAT Oncomedica Auna S.A.S.
🇨🇴Monteria, Colombia
Centro de investigaciones clínicas, fudación valle del lili
🇨🇴Cali, Colombia
Ap-Hp-Hopital Avicenne
🇫🇷Bobigny, France
Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin
🇫🇷Bordeaux, France
Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-1
🇫🇷Grenoble cedex 9, France
Hospices Civils de Lyon-Hopital Edouard Herriot
🇫🇷Lyon Cedex 03, France
Ap-Hp-Hopital Necker-1
🇫🇷Paris, France
Ap-Hp-Hopital Robert Debre
🇫🇷Paris, France
Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
🇫🇷Rouen cedex, France
Agogo Presbyterian Hospital, Ghana
🇬🇭Agogo, Ghana
Kintampo Health Research Centre (KHRC), Kintampo, Ghana
🇬🇭Kintampo, Ghana
Navrongo Health Research Centre, Ghana
🇬🇭Navrongo, Ghana
"Laiko" General Hospital of Athens
🇬🇷Athens, Greece
Childrens' Hospital of Athens "Agia Sofia"
🇬🇷Athens, Greece
Hippokration Hospital
🇬🇷Athens, Greece
University General Hospital Of Ioannina
🇬🇷Ioannina, Greece
"AHEPA" University General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Gauhati Medical College and Hospital
🇮🇳Guwahati, Assam, India
All India Institute of Medical Sciences (AIIMS), Raipur
🇮🇳Raipur, Chhattisgarh, India
Zydus Medical College & Hospital
🇮🇳Dahod, Gujarat, India
Nirmal Hospital Pvt. Ltd.
🇮🇳Surat, Gujarat, India
SSG Hospital, Baroda
🇮🇳Vadodara, Gujarat, India
HOCC Haemato Oncology Care Centre
🇮🇳Vadodara, Gujarat, India
JSS Hospital, Mysore
🇮🇳Mysuru, Karnataka, India
Government Medical College, Kozhikode
🇮🇳Kozhikode, Kerala, India
Arihant Multispeciality Hospital
🇮🇳Nagpur, Maharashtra, India
IMS and SUM Hospital
🇮🇳Bhubaneswar, Orissa, India
RNT Medical College
🇮🇳Udaipur, Rajasthan, India
NIZAM'S Institute of Medical Sciences
🇮🇳Hyderabad, Telangana, India
Post Graduate Institute of Child Health
🇮🇳Noida, Uttar Pradesh, India
All India Institute of Medical Sciences_New Dehli
🇮🇳New Delhi, India
Erasmus MC
🇳🇱Rotterdam, Netherlands
Azienda Ospedaliera Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Torino, Italy
ASST Civili di Brescia
🇮🇹Brescia, Italy
ARNAS (Azienda Ospedaliera di Rilievo Nazionale di Alta Specializzazione) Ospedale Garibaldi
🇮🇹Catania, Italy
A.O. Universitaria di Modena
🇮🇹Modena, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Italy
A.O.U. Università Studi della Campania "Luigi Vanvitelli"
🇮🇹Naples, Italy
Azienda Ospedale Universita Padova
🇮🇹Padova, Italy
Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
🇮🇹Palermo, Italy
Policlinico GB Rossi
🇮🇹Verona, Italy
Ahero Clinical Trials Unit, Kisumu, Kenya
🇰🇪Kisumu, Kenya
Gertrude's Children's Hospital, Nairobi
🇰🇪Nairobi, Kenya
KEMRI Siaya Clinical Research Annex Siaya County Referral Hospital, Siaya
🇰🇪Siaya, Kenya
International Cancer Institute (ICI)
🇰🇪Uasin Gishu County, Kenya
American University of Beirut Medical Centre
🇱🇧Hamra, Lebanon
Hospital Nini
🇱🇧Tripoli, Lebanon
Amsterdam UMC Lokatie VUMC
🇳🇱Amsterdam, Netherlands
Haga Ziekenhuis
🇳🇱Den Haag, Netherlands
University College Hospital Paediatric Haematology and Oncology Unit, Ibadan
🇳🇬Ibadan, Oyo State, Nigeria
Centre for Sickle Cell Disease Research and Training University of Abuja (CESRTA), Abuja
🇳🇬Abuja, Nigeria
University of Nigeria Teaching Hospital, Enugu
🇳🇬Enugu, Nigeria
Lagos University Teaching Hospital, Lagos
🇳🇬Lagos, Nigeria
The Royal Hospital
🇴🇲Muscat, Oman
Sultan Qaboos University Hospital
🇴🇲Muscat, Oman
King Abdulaziz Hospital-Al Ahsa-National Guard
🇸🇦Al Ahsa, Saudi Arabia
National Guard Hospital Dammam
🇸🇦Dhahran, Saudi Arabia
King Faisal Specialist Hospital & Research Centre, Riyadh
🇸🇦Riyadh, Saudi Arabia
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Acibadem Adana Hastanesi
🇹🇷Adana, Turkey
Baskent Universitesi Adana
🇹🇷Adana, Turkey
Cukurova University Medical Faculty
🇹🇷Adana, Turkey
Hacettepe University Hematology
🇹🇷Ankara, Turkey
Mersin University Medical Faculty Pediatric Hematology
🇹🇷Mersin, Turkey
VM Medical Park Mersin Hospital
🇹🇷Mersin, Turkey
Jinja Regional Referral Hospital Children's Ward
🇺🇬Jinja, Uganda
Makerere University College of Health Sciences
🇺🇬Kampala, Uganda
Joint Clinical Research Centre (JCRC)
🇺🇬Kampala, Uganda
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Whittington Hospital
🇬🇧London, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Imperial College London
🇬🇧London, United Kingdom