Clinical trial • Phase II/III • Haematology
ETAVOPIVAT for Sickle cell disease
Phase II/III trial of ETAVOPIVAT for Sickle cell disease.
Overview
- Trial Therapeutic Area
- Haematology
- Trial Disease
- Sickle cell disease
- Trial Stage
- Phase II/III
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 17-06-2024
- First CTIS Authorization Date
- 16-07-2024
Trial design
Randomised, etavopivat a 100 mg (oral tablet); etavopivat a 200 mg (oral tablet); etavopivat placebo (placebo control). dose schedules not specified in available data., adaptive Phase II/III trial across 21 sites in France, Germany, Greece and others.
- Randomised
- Yes
- Comparator
- Etavopivat A 100 mg (oral tablet); Etavopivat A 200 mg (oral tablet); Etavopivat placebo (placebo control). Dose schedules not specified in available data.
- Adaptive
- True; study described as adaptive in the title. No specific adaptive rules (e.g., dose-escalation rules, interim analysis or stopping rules) are detailed in the available CTIS data.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 356
- Trial Duration For Participant
- 364
Eligibility
Recruits 356 paediatric patients.
- Pregnancy Exclusion
- 2) Female who is breast feeding or pregnant
- Vulnerable Population
- Vulnerable population selected. The trial includes adolescents (age range includes 12-17 years). Consent requirement: 'Provision of consent' is an inclusion criterion. Assent and parent/legal guardian informed consent documents are provided (documents include L1_SIS and ICF_minor, L1_SIS and ICF_parent, L1_SIS and ICF_Assent across country-specific submissions), indicating assent for minors and parental/legal guardian consent where applicable.
Inclusion criteria
- {"criterion_text":"- 1) Provision of consent"}
- {"criterion_text":"- 2) Patient has a confirmed diagnosis of sickle cell disease"}
- {"criterion_text":"- 3) 2-15 episodes of documented vaso-occlusive crises in the past 12 months"}
- {"criterion_text":"- 4) Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL (≥ 55 and ≤ 105 g/L) during screening"}
- {"criterion_text":"- 5) Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 days prior to start of study treatment"}
- {"criterion_text":"- 6) Female patients of childbearing potential must use acceptable methods of contraception; male patients are willing to use acceptable methods of contraception"}
- {"criterion_text":"- 7)Patients on crizanlizumab or L-glutamine oral powder (Endari®) treatment at the time of consent may be eligible if they: • Have been on a stable dose for ≥ 12 months at the time of consent (i.e., no changes to the dose except for changes to weight or for safety reasons) • Have been ≥ 80% compliant with the planned regimen during the 12 months prior to the time of consent • Meet the VOC eligibility requirement in Inclusion Criterion 4."}
Exclusion criteria
- {"criterion_text":"- Medical Conditions 1) More than 15 vaso-occlusive crises within the past 12 months prior to screening"}
- {"criterion_text":"- Prior/Concomitant Therapy 1) Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)"}
- {"criterion_text":"- 2) 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"}
- {"criterion_text":"- 3) Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study"}
- {"criterion_text":"- 4) Use of an experimental selectin antagonist (e.g., monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study"}
- {"criterion_text":"- 5) Uso de eritropoyetina u otro tratamiento con factor de crecimiento hematopoyético dentro de los 28 días posteriores al inicio del tratamiento del estudio o la necesidad anticipada de dichos agentes durante el estudio."}
- {"criterion_text":"- 6) Receipt of prior cellular-based therapy (e.g., hematopoietic cell transplant, gene modification therapy)"}
- {"criterion_text":"- 2) Female who is breast feeding or pregnant"}
- {"criterion_text":"- 3) Hepatic dysfunction characterized by: - Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) OR - Direct bilirubin > 3.0 × ULN"}
- {"criterion_text":"- 4) Known HIV positive"}
- {"criterion_text":"- 5) Active hepatitis B or hepatitis C infection"}
- {"criterion_text":"- 6) Severe renal dysfunction or on chronic dialysis"}
- {"criterion_text":"- 7) 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"}
- {"criterion_text":"- 8) History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage"}
- {"criterion_text":"- 9) History of deep venous thrombosis requiring systemic anticoagulation therapy for ≥ 6 weeks, occurring within 6 months prior to Day 1 of study treatment. Note: patients on ≥ 6 months of chronic or prophylactic anti-coagulation therapy are allowed on study."}
Endpoints
Primary endpoints
- {"endpoint_text":"- • Hb response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period","definition_or_measurement_approach":"Hb response measured at Week 24 during the blinded treatment period; defined as increase of >1 g/dL (>10 g/L) from baseline."}
- {"endpoint_text":"- • Annualized VOC rate during the 52-week blinded treatment period based on adjudicated VOC review","definition_or_measurement_approach":"Annualized vaso-occlusive crisis (VOC) rate measured over the 52-week blinded treatment period, based on adjudicated VOC review."}
Secondary endpoints
- {"endpoint_text":"- 1. Change from baseline in Hb at Week 52 during the blinded treatment period","definition_or_measurement_approach":"Change from baseline in haemoglobin measured at Week 52 during the blinded treatment period."}
- {"endpoint_text":"- 2. Change in SCD-related clinical laboratory measurements from baseline at Week 24 during the blinded treatment period in: o Absolute reticulocyte count, o Indirect bilirubin, and o Lactate dehydrogenase (LDH)","definition_or_measurement_approach":"Change from baseline in absolute reticulocyte count, indirect bilirubin and LDH at Week 24 during the blinded treatment period."}
- {"endpoint_text":"- 3. Change from baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale in adult patients at Week 52 during the blinded treatment period","definition_or_measurement_approach":"Change from baseline in PROMIS Fatigue Scale in adult patients measured at Week 52 during the blinded treatment period."}
- {"endpoint_text":"- 4. Time to first VOC during the blinded treatment period","definition_or_measurement_approach":"Time-to-event measurement: time from randomization/start to first adjudicated VOC during the blinded treatment period."}
Recruitment
- Planned Sample Size
- 356
- Recruitment Window Months
- 73
- Consent Approach
- Informed consent required ('Provision of consent'). Age-specific informed consent and assent materials provided across participating countries (documents include adult ICFs, parent/legal guardian ICFs, and assent forms for minors). Country-language documents available for at least English, French, German, Greek, Italian and Spanish (patient-facing and ICF documents listed per country). Minors (e.g., 12-17) have assent forms and parent/guardian consent forms documented.
Geography
- Total Number Of Sites
- 21
- Total Number Of Participants
- 94
France
- Earliest CTIS Part Ii Submission Date
- 01-07-2024
- Latest Decision Or Authorization Date
- 20-04-2026
- Processing Time Days
- 659
- Number Of Sites
- 4
- Number Of Participants
- 19
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Unite des Maladies Genetiques du Globule Rouge
- 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
- Hospital Edouard Herriot
- Department Name
- Medecine interne
- 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
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- Medecine Interne DIAGORA
- Principal Investigator Name
- Ivan Bertchansky
- Principal Investigator Email
- i-bertchansky@chu-montpellier.fr
- Contact Person Name
- Ivan Bertchansky
- Contact Person Email
- i-bertchansky@chu-montpellier.fr
- Site Name
- Robert Debre University Hospital
- Department Name
- Centre de reference des Maladies Constitutionnelles du Globule rouge et de l Erythropoiese
- Principal Investigator Name
- Valentine Brousse
- Principal Investigator Email
- Valentine.brousse@aphp.fr
- Contact Person Name
- Valentine Brousse
- Contact Person Email
- Valentine.brousse@aphp.fr
Germany
- Earliest CTIS Part Ii Submission Date
- 01-07-2024
- Latest Decision Or Authorization Date
- 23-04-2026
- Processing Time Days
- 662
- Number Of Sites
- 3
- Number Of Participants
- 15
Sites
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Klinik fuer Paediatrie mit Schwerpunkt Onkoloige und Haemnatologie, Campus Virchow Klinikum (CVK)
- Principal Investigator Name
- Lena Oevermann
- Principal Investigator Email
- lena-oevermann@charite.de
- Contact Person Name
- Lena Oevermann
- Contact Person Email
- lena-oevermann@charite.de
- Site Name
- Medical Center - University Of Freiburg
- Department Name
- Klinik fuer Paedriatische Haematologie und Onkologie
- Principal Investigator Name
- Sara Salou
- Principal Investigator Email
- sarah.salou@unilinik-freiburg.de
- Contact Person Name
- Sara Salou
- Contact Person Email
- sarah.salou@unilinik-freiburg.de
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- Klinik fuer Onkologie, Haematologie, Immunologie und Pneumologie
- Principal Investigator Name
- Joachim Kunz
- Principal Investigator Email
- joachim.kunz@med.uni-heidelberg.de
- Contact Person Name
- Joachim Kunz
- Contact Person Email
- joachim.kunz@med.uni-heidelberg.de
Greece
- Earliest CTIS Part Ii Submission Date
- 01-07-2024
- Latest Decision Or Authorization Date
- 20-04-2026
- Processing Time Days
- 659
- Number Of Sites
- 4
- Number Of Participants
- 30
Sites
- 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
- Ippokratio General Hospital Of Thessaloniki
- Department Name
- Thalassemia Unit, 2nd Internal Medicine Clinic, Aristotle University of Thessaloniki
- Principal Investigator Name
- Efthymia Vlachaki
- Principal Investigator Email
- efivlachaki@yahoo.gr
- Contact Person Name
- Efthymia Vlachaki
- Contact Person Email
- efivlachaki@yahoo.gr
- Site Name
- General University Hospital Of Patras
- Department Name
- Hematology Clinic, Thalassemia Unit
- Principal Investigator Name
- Alexandros Spyridonidis
- Principal Investigator Email
- spyridonidis@upatras.gr
- Contact Person Name
- Alexandros Spyridonidis
- Contact Person Email
- spyridonidis@upatras.gr
- Site Name
- General Hospital Of Larissa Koutlibaneio And Triantafylleio
- Department Name
- Department of Hematology, Thalassemia and Sickle Cell Disease
- Principal Investigator Name
- Michael Diamantidis
- Principal Investigator Email
- diamantidis76@gmail.com
- Contact Person Name
- Michael Diamantidis
- Contact Person Email
- diamantidis76@gmail.com
Italy
- Earliest CTIS Part Ii Submission Date
- 01-07-2024
- Latest Decision Or Authorization Date
- 22-04-2026
- Processing Time Days
- 661
- Number Of Sites
- 5
- Number Of Participants
- 20
Sites
- Site Name
- Azienda Ospedaliero-Universitaria San Luigi Gonzaga
- Department Name
- S.S.D. Microcitemie e malattie rare ematologiche
- Principal Investigator Name
- Giovanni Battista Ferrero
- Principal Investigator Email
- giovannibattista.ferrero@unito.it
- Contact Person Name
- Giovanni Battista Ferrero
- Contact Person Email
- giovannibattista.ferrero@unito.it
- Site Name
- Bambino Gesu Childrens Hospital
- Department Name
- Dipartimento di Oncoematologia, Terapia Cellulare, Terapie Geniche e Trapianto Emopoietico
- Principal Investigator Name
- Franco Locatelli
- Principal Investigator Email
- franco.locatelli@opbg.net
- Contact Person Name
- Franco Locatelli
- Contact Person Email
- franco.locatelli@opbg.net
- Site Name
- Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
- Department Name
- UOC Ematologia ed Oncologia Pediatrica
- Principal Investigator Name
- Giovanna Russo
- Principal Investigator Email
- diberuss@unict.it
- Contact Person Name
- Giovanna Russo
- Contact Person Email
- diberuss@unict.it
- Site Name
- Fondazione IRCCS Policlinico San Matteo
- Department Name
- Dip. Materno-infantile Oncoematologia Pediatrica
- Principal Investigator Name
- Marco Zecca
- Principal Investigator Email
- m.zecca@smatteo.pv.it
- Contact Person Name
- Marco Zecca
- Contact Person Email
- m.zecca@smatteo.pv.it
- Site Name
- Azienda Ospedaliera di Padova
- Department Name
- Dipartimento della Salute della Donna e del Bambino
- Principal Investigator Name
- Raffaella Colombatti
- Principal Investigator Email
- raffaella.colombatti@unipd.it
- Contact Person Name
- Raffaella Colombatti
- Contact Person Email
- raffaella.colombatti@unipd.it
Spain
- Earliest CTIS Part Ii Submission Date
- 01-07-2024
- Latest Decision Or Authorization Date
- 21-04-2026
- Processing Time Days
- 660
- Number Of Sites
- 5
- Number Of Participants
- 10
Sites
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Hematology
- Principal Investigator Name
- Salvador Payan Pernia
- Principal Investigator Email
- pppayan@gmail.com
- Contact Person Name
- Salvador Payan Pernia
- Contact Person Email
- pppayan@gmail.com
- Site Name
- Hospital Universitario La Paz
- Department Name
- Hematology
- Principal Investigator Name
- Ana Mendoza Martínez
- Principal Investigator Email
- anamendoz94@gmail.com
- Contact Person Name
- Ana Mendoza Martínez
- Contact Person Email
- anamendoz94@gmail.com
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Hematology
- Principal Investigator Name
- Fernando Ataulfo Gonzalez Fernandez
- Principal Investigator Email
- fernandoataulfo.gonzalez@salud.madrid.org
- Contact Person Name
- Fernando Ataulfo Gonzalez Fernandez
- Contact Person Email
- fernandoataulfo.gonzalez@salud.madrid.org
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Hematology
- Principal Investigator Name
- David Beneitez Pastor
- Principal Investigator Email
- dbeneitez@vhebron.net
- Contact Person Name
- David Beneitez Pastor
- Contact Person Email
- dbeneitez@vhebron.net
- Site Name
- Hospital Universitario De Cruces
- Department Name
- Hematology
- Principal Investigator Name
- Miriam Vara Pampliega
- Principal Investigator Email
- miriam.varapampliega@osakidetza.eus
- Contact Person Name
- Miriam Vara Pampliega
- Contact Person Email
- miriam.varapampliega@osakidetza.eus
Sponsor
Primary sponsor
- Full Name
- Novo Nordisk A/S
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Denmark
Contract research organisations
- Name
- Syneos Health Netherlands B.V.
- Responsibilities
- Project Management; Trial and Site Management; Vendor Management
- Name
- Synteracthcr
- Responsibilities
- Trial and Site Management; Vendor Management
- Name
- Prometrika LLC
- Responsibilities
- Clinical services (codes: 10,6,7) as listed in sponsor duties
- Name
- PPD Global Central Labs
- Responsibilities
- Central laboratory services (PK indicated)
- Name
- Suvoda LLC
- Responsibilities
- Support services (code:3)
- Name
- Syneos Health Hellas Single Member S.A.
- Responsibilities
- Trial and Site Management
Third parties
- {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"codes: 3","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Prometrika LLC","duties_or_roles":"codes: 10, 6, 7","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Mde Services Group Limited","duties_or_roles":"Home health visits and Patient Travel Reimbursemen","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"Project Management; Trial and Site Management; Vendor Management (codes: 1,12,15,2,8,9)","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"PK; code:4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Synteracthcr","duties_or_roles":"Trial and Site Management; Vendor Management (codes: 1,12,15,5,8,9)","organisation_type":"Pharmaceutical company"}
- {"country":"Greece","full_name":"Syneos Health Hellas Single Member S.A.","duties_or_roles":"Trial and Site Management (codes: 1,12,15,2,8)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Etavopivat A 100 mg
- Active Substance
- ETAVOPIVAT
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- Authorised
- Orphan Designation
- Yes
- Starting Dose
- 100 mg
- Dose Levels
- 100 mg
- Dose Escalation Increase
- 100 mg
- Investigational Product Name
- Etavopivat A 200 mg
- Active Substance
- ETAVOPIVAT
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- Authorised
- Orphan Designation
- Yes
- Starting Dose
- 200 mg
- Dose Levels
- 200 mg
- Dose Escalation Increase
- 200 mg
- Investigational Product Name
- Etavopivat placebo.
- Modality
- Other
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