Clinical trial NCT06612268: A Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sickle Cell Disease
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2024-09-25
Enrollment: 408
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact
timeFrame: Baseline (week 0) to week 52
Secondary outcomes:
measure: Time to onset of first adjudicated Vaso-occlusive crisis (VOC)
timeFrame: Baseline (week 0) to week 52
measure: Change in distance travelled during the 6-minute walking test (6MWT)
timeFrame: Baseline (week 0) to week 52
measure: Change in standardised T-score on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a Scale
timeFrame: Baseline (week 0) to week 52
measure: Change in haemoglobin (Hb)
timeFrame: Baseline (week 0) to week 52
measure: Change in Haemoglobin (Hb) greater than 1 grams per decilitre (g/dL)
timeFrame: Baseline (week 0) to week 52
measure: Change in lactate dehydrogenase (LDH)
timeFrame: Baseline (week 0) to week 52
measure: Change in absolute reticulocyte count
timeFrame: Baseline (week 0) to week 52
measure: Change in indirect bilirubin
timeFrame: Baseline (week 0) to week 52
measure: Changes in estimated glomerular filtration rate (eGFR)
timeFrame: Baseline (week 0) to week 52
measure: Change in albumin:creatinine ratio (ACR)
timeFrame: Baseline (week 0) to week 52
measure: Occurrence of moderate/severe albuminuria (yes/no)
timeFrame: Baseline (week 0) to week 52
measure: Change in N-terminal pro b-type natriuretic peptide (NT-pro-BNP)
timeFrame: Baseline (week 0) to week 52
measure: Proportion of participants achieving the threshold for clinically meaningful change (yes/no) in PROMIS fatigue scale 7a
timeFrame: Baseline (week 0) to week 52
measure: Proportion of participants achieving the threshold for clinically meaningful change (yes/no) in 6MWT
timeFrame: Baseline (week 0) to week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Uni of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: Univer South Alabama Ped/Onc
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hsptl
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles - Endocrinology
state: California
city: Los Angeles
country: United States
facility: UCLA Health
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Orange
country: United States
facility: University Of California Irvine
state: California
city: Palo Alto
country: United States
facility: Stanford University_Palo Alto
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: Clinical and Transl Res Center
state: Colorado
city: Wilmington
country: United States
facility: Nemours/AI duPont Hosp-Chld
state: Delaware
city: Washington
country: United States
facility: Childrens National Medical Ctr
state: District of Columbia
city: Washington
country: United States
facility: MedStar Hlth Res Institute
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Healthcare
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare Atlanta
state: Georgia
city: Chicago
country: United States
facility: Childrens Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Univer Of Illinois at Chicago
state: Illinois
city: New Orleans
country: United States
facility: Children's Hosp-New Orleans
state: Louisiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital_Detroit
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University-St.Louis
state: Missouri
city: Omaha
country: United States
facility: Children's Nebraska
state: Nebraska
city: Las Vegas
country: United States
facility: Cure 4 the Kids Foundation
state: Nevada
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Ctr
state: New York
city: Brooklyn
country: United States
facility: NYC Health+Hospitals
state: New York
city: Brooklyn
country: United States
facility: Interfaith Medical Center
state: New York
city: Mount Kisco
country: United States
facility: Northwell Health
state: New York
city: Queens
country: United States
facility: Cohen Children's Medical Ctr
state: New York
city: Durham
country: United States
facility: Duke Comprehen Sickle Cell
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina Univ-Greenville
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health-Wake Forest Bapt
state: North Carolina
city: Cleveland
country: United States
facility: Univ Hosp Cleveland Med Ctr
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Wexner Med Ctr
state: Ohio
city: Oklahoma City
country: United States
facility: Univ of OK Health Sciences Ctr
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hosptl Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: St Christopher Hosp for Child
state: Pennsylvania
city: Memphis
country: United States
facility: Methodist University Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Res Hosp
state: Tennessee
city: Houston
country: United States
facility: UT Health University of Texas
state: Texas
city: Fairfax
country: United States
facility: Inova Health System
state: Virginia
city: Norfolk
country: United States
facility: Children's Hsptl Of The Kings
state: Virginia
city: Richmond
country: United States
facility: Virginia Comm Univ Medical Ctr
state: Virginia
city: Tacoma
country: United States
facility: Mary Bridge Children's Health
state: Washington
city: Tacoma
country: United States
facility: Mary Bridge Children's Health
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital - Department of Haematology
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital - Haemophilia and Haemostasis Centre
state: Western Australia
city: Bruxelles
country: Belgium
facility: CHU Saint-Pierre - UMC Sint-Pieter
city: Bruxelles
country: Belgium
facility: CHU - UVC Brugmann
city: Bruxelles
country: Belgium
facility: HUB - Hôpital Erasme
city: Edegem
country: Belgium
facility: UZ Antwerpen - UZA - Haematology
city: Edegem
country: Belgium
facility: UZ Antwerpen - UZA - Kinderhemato-Oncologie
city: Leuven
country: Belgium
facility: UZ Leuven - Kindergeneeskunde
city: Recife
country: Brazil
facility: MultiHemo - Grupo Oncoclínicas
state: Pernambuco
city: São Paulo
country: Brazil
facility: HC da FMUSP Hospital das Clínicas São Paulo
state: SP
city: Distrito De Barão Geraldo - Campinas
country: Brazil
facility: Hemocentro UNICAMP
state: São Paulo
city: Ribeirão Preto
country: Brazil
facility: Fundação Hemocentro de Ribeirão Preto
state: São
city: Rio de Janeiro
country: Brazil
facility: Hemorio-Fundarj
city: São Paulo
country: Brazil
facility: Hospital Samaritano Higienópolis - Instituto de Conhecimento Ensino e Pesquisa (ICEP)
city: Calgary
country: Canada
facility: Foothills Med Ctr-Univ Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta_Edmonton
state: Alberta
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: London
country: Canada
facility: LHSC - Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: UHN-Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
city: Montreal
country: Canada
facility: CHUM-Hosp de Univ Montreal
state: Quebec
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
state: Antioquia
city: Barranquilla
country: Colombia
facility: Clinica de la Costa
state: Atlántico
city: Valledupar
country: Colombia
facility: Sociedad de Oncología y Hematología del Cesar SAS (SOHEC)
state: Cesar
city: Monteria
country: Colombia
facility: Clínica IMAT Oncomedica Auna S.A.S.
state: Córdoba
city: Cali
country: Colombia
facility: Centro de investigaciones clínicas, fudación valle del lili
state: Valle Del Cauca
city: Antioquia
country: Colombia
facility: Sociedad de Oncología y Hematología del Cesar SAS (SOHEC)
city: Cali
country: Colombia
facility: Centro de investigaciones clínicas, fudación valle del lili
city: Monteria
country: Colombia
facility: Clínica IMAT Oncomedica Auna S.A.S.
city: Bobigny
country: France
facility: Ap-Hp-Hopital Avicenne
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin
city: Créteil
country: France
facility: Ap-Hp-Hopital Henri Mondor
city: Grenoble cedex 9
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-1
city: Lyon Cedex 03
country: France
facility: Hospices Civils de Lyon-Hopital Edouard Herriot
city: Paris
country: France
facility: Ap-Hp-Hopital Necker-1
city: Paris
country: France
facility: Ap-Hp-Hopital Robert Debre
city: Rouen cedex
country: France
facility: Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
city: Agogo
country: Ghana
facility: Agogo Presbyterian Hospital, Ghana
city: Kintampo
country: Ghana
facility: Kintampo Health Research Centre (KHRC), Kintampo, Ghana
city: Navrongo
country: Ghana
facility: Navrongo Health Research Centre, Ghana
city: Athens
country: Greece
facility: "Laiko" General Hospital of Athens
city: Athens
country: Greece
facility: Childrens' Hospital of Athens "Agia Sofia"
city: Athens
country: Greece
facility: Hippokration Hospital
city: Ioannina
country: Greece
facility: University General Hospital Of Ioannina
city: Thessaloniki
country: Greece
facility: "AHEPA" University General Hospital of Thessaloniki
city: Guwahati
country: India
facility: Gauhati Medical College and Hospital
state: Assam
city: Raipur
country: India
facility: All India Institute of Medical Sciences (AIIMS), Raipur
state: Chhattisgarh
city: Dahod
country: India
facility: Zydus Medical College & Hospital
state: Gujarat
city: Surat
country: India
facility: Nirmal Hospital Pvt. Ltd.
state: Gujarat
city: Vadodara
country: India
facility: SSG Hospital, Baroda
state: Gujarat
city: Vadodara
country: India
facility: HOCC Haemato Oncology Care Centre
state: Gujarat
city: Mysuru
country: India
facility: JSS Hospital, Mysore
state: Karnataka
city: Kozhikode
country: India
facility: Government Medical College, Kozhikode
state: Kerala
city: Nagpur
country: India
facility: Arihant Multispeciality Hospital
state: Maharashtra
city: Bhubaneswar
country: India
facility: IMS and SUM Hospital
state: Orissa
city: Udaipur
country: India
facility: RNT Medical College
state: Rajasthan
city: Hyderabad
country: India
facility: NIZAM'S Institute of Medical Sciences
state: Telangana
city: Noida
country: India
facility: Post Graduate Institute of Child Health
state: Uttar Pradesh
city: New Delhi
country: India
facility: All India Institute of Medical Sciences_New Dehli
city: Orbassano
country: Italy
facility: Azienda Ospedaliera Universitaria San Luigi Gonzaga
state: Torino
city: Brescia
country: Italy
facility: ASST Civili di Brescia
city: Catania
country: Italy
facility: ARNAS (Azienda Ospedaliera di Rilievo Nazionale di Alta Specializzazione) Ospedale Garibaldi
city: Modena
country: Italy
facility: A.O. Universitaria di Modena
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Naples
country: Italy
facility: A.O.U. Università Studi della Campania "Luigi Vanvitelli"
city: Padova
country: Italy
facility: Azienda Ospedale Universita Padova
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
city: Verona
country: Italy
facility: Policlinico GB Rossi
city: Kisumu
country: Kenya
facility: Ahero Clinical Trials Unit, Kisumu, Kenya
city: Nairobi
country: Kenya
facility: Gertrude's Children's Hospital, Nairobi
city: Siaya
country: Kenya
facility: KEMRI Siaya Clinical Research Annex Siaya County Referral Hospital, Siaya
city: Uasin Gishu County
country: Kenya
facility: International Cancer Institute (ICI)
city: Hamra
country: Lebanon
facility: American University of Beirut Medical Centre
city: Tripoli
country: Lebanon
facility: Hospital Nini
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Lokatie VUMC
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: UMC Utrecht, Van Creveldkliniek
city: Ibadan
country: Nigeria
facility: University College Hospital Paediatric Haematology and Oncology Unit, Ibadan
state: Oyo State
city: Abuja
country: Nigeria
facility: Centre for Sickle Cell Disease Research and Training University of Abuja (CESRTA), Abuja
city: Enugu
country: Nigeria
facility: University of Nigeria Teaching Hospital, Enugu
city: Lagos
country: Nigeria
facility: Lagos University Teaching Hospital, Lagos
city: Muscat
country: Oman
facility: The Royal Hospital
city: Muscat
country: Oman
facility: Sultan Qaboos University Hospital
city: Al Ahsa
country: Saudi Arabia
facility: King Abdulaziz Hospital-Al Ahsa-National Guard
city: Dhahran
country: Saudi Arabia
facility: National Guard Hospital Dammam
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Centre, Riyadh
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi
city: Adana
country: Turkey
facility: Baskent Universitesi Adana
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty
city: Ankara
country: Turkey
facility: Hacettepe University Hematology
city: Mersin
country: Turkey
facility: Mersin University Medical Faculty Pediatric Hematology
city: Mersin
country: Turkey
facility: Mersin University Medical Faculty Pediatric Hematology
city: Mersin
country: Turkey
facility: VM Medical Park Mersin Hospital
city: Jinja
country: Uganda
facility: Jinja Regional Referral Hospital Children's Ward
city: Kampala
country: Uganda
facility: Makerere University College of Health Sciences
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre (JCRC)
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: Whittington Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: