Clinical trial • Phase III • Haematology|Rare Disease
ETAVOPIVAT for Sickle cell disease
Phase III trial of ETAVOPIVAT for Sickle cell disease.
Overview
- Trial Therapeutic Area
- Haematology|Rare Disease
- Trial Disease
- Sickle cell disease
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 11-11-2024
- First CTIS Authorization Date
- 18-03-2025
Trial design
Randomised, placebo (matching placebo) comparator arm; active investigational product: etavopivat a 200 mg oral tablet (etavopivat a 200 mg).-controlled Phase III trial in Belgium, Italy, Netherlands and others.
- Randomised
- Yes
- Comparator
- Placebo (matching placebo) comparator arm; active investigational product: Etavopivat A 200 mg oral tablet (Etavopivat A 200 mg).
- Target Sample Size
- 333
Eligibility
Recruits 333 paediatric patients.
- Vulnerable Population
- Study includes adolescents (12-17 years). Subject information and informed consent documents for adolescents (12-17 years), parents/guardians and legal authorised representatives (LAR) are included in the application (country-specific PIIC/consent forms listed). Vulnerable-population procedures include parent/guardian/LAR consent materials and adolescent information/assent documents (multiple language versions available).
Inclusion criteria
- {"criterion_text":"- Male or female\n- Age 12 years or above at the time of signing the informed consent\n- Confirmed diagnosis of sickle cell disease (SCD): Documentation of 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.\n- Have 2−15 episodes of documented vaso-occlusive crises (VOCs) 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.\n- Hb ≥5.0 and ≤10.0 g/dL (≥50 and ≤100 g/L) at screening."}
Exclusion criteria
- {"criterion_text":"- Use of voxelotor or similar agent within 28 days prior to starting study treatment or anticipated need for this agent during the study\n- Severe renal dysfunction (estimated glomerular filtration rate [eGFR] at screening, calculated by the central laboratory <30 mL/min/1.73 m2) or on chronic dialysis.\n- Travelled distance on standardized 6-minute walking test below 100m at screening.\n- 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.\n- Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or ≥6 transfusion events in the previous 12 months (i.e., an average of 1 transfusion event every 60 days).\n- 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 Hb) <10% by Hb electrophoresis is documented prior to starting study treatment.\n- Receiving or use of concomitant medications that are strong inducers of CYP3A4 within 2 weeks of starting study treatment or anticipated need for such agents during the study.\n- 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.\n- Receipt of prior cellular-based therapy (e.g., haematopoietic cell transplant, gene modification therapy).\n- Hepatic dysfunction characterized by: Alanine aminotransferase (ALT) >4.0 × upper limit of normal (ULN) or Direct bilirubin >3.0 × ULN.\n- 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."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Number of adjudicated VOC events with a medical contact.","definition_or_measurement_approach":"Count of adjudicated vaso-occlusive crisis (VOC) events with a medical contact (as written in the primary endpoint)."}
Secondary endpoints
- {"endpoint_text":"- Change in Hb >1 g/dL (yes/no)","definition_or_measurement_approach":"Binary assessment of whether haemoglobin change is greater than 1 g/dL."}
- {"endpoint_text":"- Time to onset of first adjudicated VOC.","definition_or_measurement_approach":"Time-to-event measurement from randomisation to first adjudicated VOC."}
- {"endpoint_text":"- Change in standardised T-score on the PROMIS Fatigue 7a Scale.","definition_or_measurement_approach":"Change in PROMIS Fatigue 7a T-score from baseline to assessment timepoint."}
- {"endpoint_text":"- Change in haemoglobin (Hb)","definition_or_measurement_approach":"Continuous change in haemoglobin concentration from baseline."}
- {"endpoint_text":"- Change in lactate dehydrogenase (LDH)","definition_or_measurement_approach":"Change in LDH from baseline (laboratory measurement)."}
- {"endpoint_text":"- Change in absolute reticulocyte count","definition_or_measurement_approach":"Change in absolute reticulocyte count from baseline (laboratory measurement)."}
- {"endpoint_text":"- Change in indirect bilirubin","definition_or_measurement_approach":"Change in indirect bilirubin from baseline (laboratory measurement)."}
- {"endpoint_text":"- Change in distance travelled during the 6-minute walking test (6MWT)","definition_or_measurement_approach":"Change in 6MWT distance (meters) from baseline."}
- {"endpoint_text":"- Participants achieving the threshold for clinically meaningful change (yes/no) in PROMIS fatigue scale 7a","definition_or_measurement_approach":"Proportion achieving predefined clinically meaningful change threshold on PROMIS Fatigue 7a (yes/no)."}
- {"endpoint_text":"- Participants achieving the threshold for clinically meaningful change (yes/no) in 6MWT","definition_or_measurement_approach":"Proportion achieving predefined clinically meaningful change threshold on 6MWT (yes/no)."}
Recruitment
- Planned Sample Size
- 333
- Recruitment Window Months
- 45
- Consent Approach
- Adults provide informed consent. Adolescents (12-17) have age-specific participant information and consent/assent forms; parent/guardian and legal authorised representative (LAR) consent forms are provided. Multiple country/language PIIC documents are included (English, French, Dutch, Italian, Spanish, Greek as per submitted subject information and consent form documents).
Geography
- Total Number Of Sites
- 36
- Total Number Of Participants
- 75
Belgium
- Earliest CTIS Part Ii Submission Date
- 06-03-2025
- Latest Decision Or Authorization Date
- 18-09-2025
- Processing Time Days
- 196
- Number Of Sites
- 6
- Number Of Participants
- 10
Sites
- Site Name
- Association Hospitaliere De Bruxelles Hopital Universitaire Des Enfants Reine Fabiola
- Principal Investigator Name
- Laurence Dedeken
- Principal Investigator Email
- laurence.dedeken@hubruxelles.be
- Contact Person Name
- Laurence Dedeken
- Contact Person Email
- laurence.dedeken@hubruxelles.be
- Site Name
- Hopital Erasme
- Principal Investigator Name
- Martin Colard
- Principal Investigator Email
- martin.colard@hubruxelles.be
- Contact Person Name
- Martin Colard
- Contact Person Email
- martin.colard@hubruxelles.be
- Site Name
- Universitair Ziekenhuis Antwerpen
- Principal Investigator Name
- Philip Maes
- Principal Investigator Email
- philip.maes@uza.be
- Contact Person Name
- Philip Maes
- Contact Person Email
- philip.maes@uza.be
- Site Name
- Antwerp University Hospital
- Principal Investigator Name
- Ann Van De Velde
- Principal Investigator Email
- ann.vandevelde@uza.be
- Contact Person Name
- Ann Van De Velde
- Contact Person Email
- ann.vandevelde@uza.be
- Site Name
- UZ Leuven
- Principal Investigator Name
- Veerle Labarque
- Principal Investigator Email
- veerle.labarque@uzleuven.be
- Contact Person Name
- Veerle Labarque
- Contact Person Email
- veerle.labarque@uzleuven.be
- Site Name
- CHU Saint Pierre
- Principal Investigator Name
- Anna Vanderfaeillie
- Principal Investigator Email
- anna.vanderfaeillie@stpierre-bru.be
- Contact Person Name
- Anna Vanderfaeillie
- Contact Person Email
- anna.vanderfaeillie@stpierre-bru.be
Italy
- Earliest CTIS Part Ii Submission Date
- 24-02-2025
- Latest Decision Or Authorization Date
- 19-09-2025
- Processing Time Days
- 207
- Number Of Sites
- 9
- Number Of Participants
- 20
Sites
- Site Name
- Azienda Ospedaliero-Universitaria San Luigi Gonzaga
- Principal Investigator Name
- Vincenzo Voi
- Principal Investigator Email
- vincenzo.voi@unito.it
- Contact Person Name
- Vincenzo Voi
- Contact Person Email
- vincenzo.voi@unito.it
- Site Name
- Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
- Principal Investigator Name
- Elisa Bertoni
- Principal Investigator Email
- elisa.bertoni@asst-spedalicivili.it
- Contact Person Name
- Elisa Bertoni
- Contact Person Email
- elisa.bertoni@asst-spedalicivili.it
- Site Name
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
- Principal Investigator Name
- Rosario Di Maggio
- Principal Investigator Email
- rdm83@hotmail.it
- Contact Person Name
- Rosario Di Maggio
- Contact Person Email
- rdm83@hotmail.it
- Site Name
- Fondazione IRCCS San Gerardo Dei Tintori
- Principal Investigator Name
- Paola Consuelo Corti
- Principal Investigator Email
- paolaconsuelo.corti@irccs-sangerardo.it
- Contact Person Name
- Paola Consuelo Corti
- Contact Person Email
- paolaconsuelo.corti@irccs-sangerardo.it
- Site Name
- Centro Ricerche Cliniche Di Verona S.r.l.
- Principal Investigator Name
- Lucia De Franceschi
- Principal Investigator Email
- lucia.defranceschi@univr.it
- Contact Person Name
- Lucia De Franceschi
- Contact Person Email
- lucia.defranceschi@univr.it
- Site Name
- ARNAS Garibaldi Di Catania
- Principal Investigator Name
- Roberto Lisi
- Principal Investigator Email
- talassemia@ao-garibaldi.ct.it
- Contact Person Name
- Roberto Lisi
- Contact Person Email
- talassemia@ao-garibaldi.ct.it
- Site Name
- Azienda Ospedaliero Universitaria Di Modena
- Principal Investigator Name
- Giovanni Palazzi
- Principal Investigator Email
- palazzi.giovanni@aou.mo.it
- Contact Person Name
- Giovanni Palazzi
- Contact Person Email
- palazzi.giovanni@aou.mo.it
- Site Name
- Azienda Ospedaliera Universita' Degli Studi Della Campania Luigi Vanvitelli
- Principal Investigator Name
- Maddalena Casale
- Principal Investigator Email
- maddalena.casale@unicampania.it
- Contact Person Name
- Maddalena Casale
- Contact Person Email
- maddalena.casale@unicampania.it
- Site Name
- Azienda Ospedaliera di Padova
- Principal Investigator Name
- Raffaella Colombatti
- Principal Investigator Email
- raffaella.colombatti@unipd.it
- Contact Person Name
- Raffaella Colombatti
- Contact Person Email
- raffaella.colombatti@unipd.it
Netherlands
- Earliest CTIS Part Ii Submission Date
- 24-02-2025
- Latest Decision Or Authorization Date
- 17-09-2025
- Processing Time Days
- 205
- Number Of Sites
- 4
- Number Of Participants
- 10
Sites
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Principal Investigator Name
- Anita Rijneveld
- Principal Investigator Email
- a.rijneveld@erasmusmc.nl
- Contact Person Name
- Anita Rijneveld
- Contact Person Email
- a.rijneveld@erasmusmc.nl
- Site Name
- Amsterdam UMC Stichting
- Principal Investigator Name
- Bart Biemond
- Principal Investigator Email
- hematology@amsterdamumc.nl
- Contact Person Name
- Bart Biemond
- Contact Person Email
- hematology@amsterdamumc.nl
- Site Name
- Universitair Medisch Centrum Utrecht
- Principal Investigator Name
- E.J. Van Beers
- Principal Investigator Email
- e.j.vanbeers-3@umcutrecht.nl
- Contact Person Name
- E.J. Van Beers
- Contact Person Email
- e.j.vanbeers-3@umcutrecht.nl
- Site Name
- Haga Hospital
- Principal Investigator Name
- Jean Louis Kerkhoffs
- Principal Investigator Email
- j.kerkhoffs@hagaziekenhuis.nl
- Contact Person Name
- Jean Louis Kerkhoffs
- Contact Person Email
- j.kerkhoffs@hagaziekenhuis.nl
Greece
- Earliest CTIS Part Ii Submission Date
- 17-01-2025
- Latest Decision Or Authorization Date
- 19-09-2025
- Processing Time Days
- 245
- Number Of Sites
- 5
- Number Of Participants
- 15
Sites
- Site Name
- University General Hospital Of Ioannina
- Department Name
- Department of Hematology
- Principal Investigator Name
- Eleni Kapsali
- Principal Investigator Email
- elkapsali@gmail.com
- Contact Person Name
- Eleni Kapsali
- Contact Person Email
- elkapsali@gmail.com
- Site Name
- University General Hospital Of Thessaloniki Ahepa
- Department Name
- Thalassemia Unit, 1st Department of Internal Medicine
- Principal Investigator Name
- Despoina Pantelidou
- Principal Investigator Email
- dpantelidou@yahoo.gr
- Contact Person Name
- Despoina Pantelidou
- Contact Person Email
- dpantelidou@yahoo.gr
- Site Name
- Hippokration Hospital
- Department Name
- Thalassemia and Sickle Cell Unit
- Principal Investigator Name
- Sophia Delicou
- Principal Investigator Email
- sophiadelicou@gmail.com
- Contact Person Name
- Sophia Delicou
- Contact Person Email
- sophiadelicou@gmail.com
- Site Name
- Laiko General Hospital Of Athens
- Department Name
- Thalassemia Unit, Center of Expertise in Hemoglobinopathies
- Principal Investigator Name
- Maria Dimopoulou
- Principal Investigator Email
- mdimkma@gmail.com
- Contact Person Name
- Maria Dimopoulou
- Contact Person Email
- mdimkma@gmail.com
- Site Name
- Nosokomeio Paidon I Agia Sofia
- Department Name
- Thalassemia Unit, First Department of Pediatrics
- Principal Investigator Name
- Antonis Kattamis
- Principal Investigator Email
- ankatt@med.uoa.gr
- Contact Person Name
- Antonis Kattamis
- Contact Person Email
- ankatt@med.uoa.gr
France
- Earliest CTIS Part Ii Submission Date
- 18-02-2025
- Latest Decision Or Authorization Date
- 24-09-2025
- Processing Time Days
- 218
- Number Of Sites
- 8
- Number Of Participants
- 12
Sites
- Site Name
- Centre Hospitalier Universitaire De Bordeaux
- Principal Investigator Name
- Arnaud Desclaux
- Principal Investigator Email
- arnaud.desclaux@chu-bordeaux.fr
- Contact Person Name
- Arnaud Desclaux
- Contact Person Email
- arnaud.desclaux@chu-bordeaux.fr
- Site Name
- Centre Hospitalier Universitaire Grenoble Alpes
- Principal Investigator Name
- Caroline Makowski
- Principal Investigator Email
- cmakowski@chu-grenoble.fr
- Contact Person Name
- Caroline Makowski
- Contact Person Email
- cmakowski@chu-grenoble.fr
- Site Name
- Assistance Publique Hopitaux De Paris (Paris site)
- Principal Investigator Name
- Laure Joseph
- Principal Investigator Email
- laure.joseph@aphp.fr
- Contact Person Name
- Laure Joseph
- Contact Person Email
- laure.joseph@aphp.fr
- Site Name
- Hospices Civils De Lyon
- Principal Investigator Name
- Giovanna Cannas
- Principal Investigator Email
- giovanna.cannas@chu-lyon.fr
- Contact Person Name
- Giovanna Cannas
- Contact Person Email
- giovanna.cannas@chu-lyon.fr
- Site Name
- Assistance Publique Hopitaux De Paris (Boulevard Serurier site)
- Principal Investigator Name
- Valentine Brousse
- Principal Investigator Email
- valentine.brousse@aphp.fr
- Contact Person Name
- Valentine Brousse
- Contact Person Email
- valentine.brousse@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris (Creteil site)
- Principal Investigator Name
- Pablo Bartolucci
- Principal Investigator Email
- pablo.bartolucci@aphp.fr
- Contact Person Name
- Pablo Bartolucci
- Contact Person Email
- pablo.bartolucci@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris (Bobigny site)
- Principal Investigator Name
- Sylvain Le Jeune
- Principal Investigator Email
- sylvain.le-jeune@aphp.fr
- Contact Person Name
- Sylvain Le Jeune
- Contact Person Email
- sylvain.le-jeune@aphp.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Principal Investigator Name
- Cécile Dumesnil De Maricourt
- Principal Investigator Email
- Cecile.Dumesnil@chu-rouen.fr
- Contact Person Name
- Cécile Dumesnil De Maricourt
- Contact Person Email
- Cecile.Dumesnil@chu-rouen.fr
Spain
- Earliest CTIS Part Ii Submission Date
- 30-01-2025
- Latest Decision Or Authorization Date
- 28-01-2026
- Processing Time Days
- 363
- Number Of Sites
- 4
- Number Of Participants
- 8
Sites
- Site Name
- Hospital Universitario La Paz
- Principal Investigator Name
- Ana Mendoza
- Principal Investigator Email
- amendozam.externo@salud.madrid.org
- Contact Person Name
- Ana Mendoza
- Contact Person Email
- amendozam.externo@salud.madrid.org
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Principal Investigator Name
- Salvador Payan Pernia
- Principal Investigator Email
- salvador.payan.sspa@juntadeandalucia.es
- Contact Person Name
- Salvador Payan Pernia
- Contact Person Email
- salvador.payan.sspa@juntadeandalucia.es
- Site Name
- Hospital General Universitario Gregorio Maranon
- Principal Investigator Name
- Elena Cela de Julian
- Principal Investigator Email
- elena.cela@salud.madrid.org
- Contact Person Name
- Elena Cela de Julian
- Contact Person Email
- elena.cela@salud.madrid.org
- Site Name
- Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca
- Principal Investigator Name
- David Beneitez Pastor
- Principal Investigator Email
- david.beneitez@vallhebron.cat
- Contact Person Name
- David Beneitez Pastor
- Contact Person Email
- david.beneitez@vallhebron.cat
Sponsor
Primary sponsor
- Full Name
- Novo Nordisk A/S
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Denmark
Contract research organisations
- Name
- IQVIA Limited
- Responsibilities
- Central Laboratory, Feasibility Consulting Services
- Name
- Icon Clinical Research Limited
- Responsibilities
- Event Adjudication Services
- Name
- 4G Clinical B.V.
- Responsibilities
- RTSM supplier and RTSM helpdesk
- Name
- Signant Health Management Limited
- Responsibilities
- eCOA
- Name
- Oracle Corporation UK Limited
- Responsibilities
- CRF supplier
Third parties
- {"country":"Greece","full_name":"Affidea Piraeus Biopathological","duties_or_roles":"Hospital/Clinic/Other health care facility (local laboratory contact listed)","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Central Laboratory, Feasibility Consulting Services","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Oracle Corporation UK Limited","duties_or_roles":"CRF supplier","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Event Adjudication Services","organisation_type":"Pharmaceutical company"}
- {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"RTSM supplier and RTSM helpdesk","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"eCOA","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Etavopivat A 200 mg
- Active Substance
- ETAVOPIVAT
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Unauthorized (investigational product in this trial)
- Orphan Designation
- Yes
- Starting Dose
- 200 mg
- Dose Levels
- 200 mg
- Investigational Product Name
- Placebo
- Modality
- Other
- Authorisation Status
- Not applicable
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