Clinical trial • Phase III • Haematology
MITAPIVAT for Non-transfusion-dependent alpha thalassemia | Non-transfusion-dependent beta thalassemia
Phase III trial of MITAPIVAT for Non-transfusion-dependent alpha thalassemia | Non-transfusion-dependent beta thalassemia.
Overview
- Trial Therapeutic Area
- Haematology
- Trial Disease
- Non-transfusion-dependent alpha thalassemia | Non-transfusion-dependent beta thalassemia
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 25-06-2024
- First CTIS Authorization Date
- 23-07-2024
Trial design
Randomised, placebo for mitapivat (oral placebo arm). dose and schedule not specified in the available data.-controlled Phase III trial in Denmark, Bulgaria, France and others.
- Randomised
- Yes
- Comparator
- Placebo for Mitapivat (oral placebo arm). Dose and schedule not specified in the available data.
- Target Sample Size
- 86
Eligibility
Recruits 86 Vulnerable population selected. Written informed consent is required from each participant prior to any study-related procedures. There is a specific informed consent document for holders of parental authority (document: 'L1_SIS and ICF Holders of parental authority_Redacted'). Subjects who are institutionalized by regulatory or court order or who have conditions that could create undue influence (including incarceration and involuntary psychiatric confinement) are excluded..
- Pregnancy Exclusion
- Pregnant, breastfeeding, or parturient.
- Vulnerable Population
- Vulnerable population selected. Written informed consent is required from each participant prior to any study-related procedures. There is a specific informed consent document for holders of parental authority (document: 'L1_SIS and ICF Holders of parental authority_Redacted'). Subjects who are institutionalized by regulatory or court order or who have conditions that could create undue influence (including incarceration and involuntary psychiatric confinement) are excluded.
Inclusion criteria
- {"criterion_text":"- ≥18 years of age at the time of providing informed consent."}
- {"criterion_text":"- Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, HbE/β-thalassemia, or α-thalassemia/HbH disease) based on Hb electrophoresis, Hb high-performance liquid chromatography, and/or DNA analysis from the subject’s medical record. If this information is not available from the subject’s medical record, the test(s) can be performed by a local laboratory during the Screening Period. If a local laboratory is unable to perform the test(s), results from the comprehensive α- and β-globin genotyping performed by the study central laboratory can be used."}
- {"criterion_text":"- Hb concentration ≤10.0 g/dL (100.0 g/L), based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period."}
- {"criterion_text":"- Non–transfusion dependent, defined as: ≤5 red blood cell (RBC) units during the 24-week period before randomization and no RBC transfusions ≤8 weeks before providing informed consent and no RBC transfusions during the Screening Period."}
- {"criterion_text":"- If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization."}
- {"criterion_text":"- Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can be an acceptable barrier method."}
- {"criterion_text":"- Written informed consent before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study."}
Exclusion criteria
- {"criterion_text":"- Pregnant, breastfeeding, or parturient."}
- {"criterion_text":"- Nonfasting triglycerides >440 mg/dL (5 mmol/L)."}
- {"criterion_text":"- Active infection requiring systemic antimicrobial therapy at the time of providing informed consent. If antimicrobial therapy is required during the Screening Period, screening procedures should not be performed while antimicrobial therapy is being administered, and the last dose of antimicrobial therapy must be administered ≥7 days before randomization."}
- {"criterion_text":"- Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen."}
- {"criterion_text":"- Positive test for HIV-1 Ab or HIV-2 Ab."}
- {"criterion_text":"- History of major surgery (including splenectomy) ≤16 weeks before providing informed consent and/or a major surgical procedure planned during the study."}
- {"criterion_text":"- Current enrollment or past participation (≤12 weeks before administration of the first dose of study drug or a time frame equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational treatment or device."}
- {"criterion_text":"- Receiving strong cytochrome P450 (CYP)3A4/5 inhibitors that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer), or strong CYP3A4 inducers that have not been stopped for ≥4 weeks or a time frame equivalent to 5 half-lives (whichever is longer), before randomization."}
- {"criterion_text":"- Receiving anabolic steroids, that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed; the testosterone dose and preparation must be stable for ≥10 weeks before randomization."}
- {"criterion_text":"- Known allergy, or other contraindication, to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and Opadry® II Blue [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD&C Blue #2])."}
- {"criterion_text":"- Any medical, hematological, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are: • Subjects who are institutionalized by regulatory or court order • Subjects with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor)."}
- {"criterion_text":"- Documented history of homozygous or heterozygous HbS or HbC."}
- {"criterion_text":"- Prior exposure to gene therapy or prior bone marrow or stem cell transplantation."}
- {"criterion_text":"- Currently receiving treatment with luspatercept; the last dose must have been administered ≥18 weeks before randomization."}
- {"criterion_text":"- Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥18 weeks before randomization."}
- {"criterion_text":"- History of malignancy (active or treated) ≤5 years before providing informed consent, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ."}
- {"criterion_text":"- History of active and/or uncontrolled cardiac or pulmonary disease ≤6 months before providing informed consent, including but not limited to: a. New York Heart Association Class III or IV heart failure or clinically significant dysrhythmia b. Myocardial infarction or unstable angina pectoris; hemorrhagic, embolic, or thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism c. Heart rate–corrected QT interval using Fridericia’s method ≥450 milliseconds (males) or ≥470 milliseconds (females), except for right or left bundle branch block d. Severe pulmonary fibrosis as defined by severe hypoxia, evidence of right-sided heart failure, and radiographic pulmonary fibrosis >50% e. Severe pulmonary hypertension as defined by severe symptoms associated with hypoxia, right-sided heart failure, and oxygen indicated"}
- {"criterion_text":"- Hepatobiliary disorders, including but not limited to: a. Liver disease with histopathological evidence of cirrhosis or severe fibrosis b. Clinically symptomatic cholelithiasis or cholecystitis (prior cholecystectomy is not exclusionary) c. History of drug-induced cholestatic hepatitis d. Aspartate aminotransferase >2.5 × upper limit of normal (ULN); unless due to hemolysis and hepatic iron deposition) and alanine aminotransferase >2.5 × ULN (unless due to hepatic iron deposition)."}
- {"criterion_text":"- Estimated glomerular filtration rate <45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration creatinine equation."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Hemoglobin (Hb) response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with baseline","definition_or_measurement_approach":"Average Hb concentration measured from Week 12 through Week 24 compared with baseline; endpoint defined as ≥1.0 g/dL increase."}
Recruitment
- Digital Remote Recruitment
- Yes
- Planned Sample Size
- 86
- Recruitment Window Months
- 87
- Consent Approach
- Written informed consent required before any study-related procedures. Participant provides consent. There are country/language-specific ICFs and SIS documents (examples in the public documents list include English, Bulgarian, Dutch, French, Greek, Spanish, Italian versions). A specific ICF for holders of parental authority is present ('L1_SIS and ICF Holders of parental authority_Redacted'). eConsent support is provided (Medidata Solutions listed with duties 'ePRO, eConsent').
Geography
- Total Number Of Sites
- 23
- Total Number Of Participants
- 86
Denmark
- Earliest CTIS Part Ii Submission Date
- 04-07-2024
- Latest Decision Or Authorization Date
- 28-10-2025
- Processing Time Days
- 481
- Number Of Sites
- 1
- Number Of Participants
- 6
Sites
- Site Name
- Rigshospitalet
- Department Name
- Department of Heamatology
- Principal Investigator Name
- Andreas Glenthøj
- Principal Investigator Email
- andreas.glenthoej@regionh.dk
- Contact Person Name
- Andreas Glenthøj
- Contact Person Email
- andreas.glenthoej@regionh.dk
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 04-07-2024
- Latest Decision Or Authorization Date
- 03-11-2025
- Processing Time Days
- 487
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- National Specialised Hospital For Active Treatment Of Haematological Diseases
- Department Name
- Department of Hematopoietic Stem Cell Transplantation
- Principal Investigator Name
- Penka Ganeva
- Principal Investigator Email
- ganevapenka@yahoo.com
- Contact Person Name
- Penka Ganeva
- Contact Person Email
- ganevapenka@yahoo.com
- Site Name
- Multiprofile Hospital For Active Treatment Dr Nikola Vasiliev AD
- Department Name
- Department of Transfusion Hematology
- Principal Investigator Name
- Desislava Ilieva-Chiviyska
- Principal Investigator Email
- dr.desislava.ilieva.chiviyska@gmail.com
- Contact Person Name
- Desislava Ilieva-Chiviyska
- Contact Person Email
- dr.desislava.ilieva.chiviyska@gmail.com
France
- Earliest CTIS Part Ii Submission Date
- 04-07-2024
- Latest Decision Or Authorization Date
- 30-10-2025
- Processing Time Days
- 483
- Number Of Sites
- 2
- Number Of Participants
- 6
Sites
- Site Name
- Hospices Civils De Lyon
- Department Name
- Hematology
- 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
- Department Name
- Hematology
- Principal Investigator Name
- Pablo Bartolucci
- Principal Investigator Email
- pablo.bartolucci@aphp.fr
- Contact Person Name
- Pablo Bartolucci
- Contact Person Email
- pablo.bartolucci@aphp.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 04-07-2024
- Latest Decision Or Authorization Date
- 29-10-2025
- Processing Time Days
- 482
- Number Of Sites
- 8
- Number Of Participants
- 29
Sites
- Site Name
- Azienda Sanitaria Locale Br
- Department Name
- U.O.C di Ematologia
- Principal Investigator Name
- Domenico Pastore
- Principal Investigator Email
- domenico.pastore0@gmail.com
- Contact Person Name
- Domenico Pastore
- Contact Person Email
- domenico.pastore0@gmail.com
- Site Name
- Azienda Ospedaliero-Universitaria San Luigi Gonzaga
- Department Name
- SSD Microcitemie
- 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
- Ente Ospedaliero Ospedali Galliera Di Genova
- Department Name
- S.S.D. Microcitemia Anemie Congenite e Dismetabolismo del ferro
- Principal Investigator Name
- Manuela Balocco
- Principal Investigator Email
- manuela.balocco@galliera.it
- Contact Person Name
- Manuela Balocco
- Contact Person Email
- manuela.balocco@galliera.it
- Site Name
- Azienda Ospedaliera Universita' Degli Studi Della Campania Luigi Vanvitelli
- Department Name
- DAI Materno Infantile
- Principal Investigator Name
- Silverio Perrotta
- Principal Investigator Email
- roberto.alfano@unicampania.it
- Contact Person Name
- Silverio Perrotta
- Contact Person Email
- roberto.alfano@unicampania.it
- Site Name
- Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
- Department Name
- UOSD Malattie Rare del Globulo Rosso
- Principal Investigator Name
- Paolo Ricchi
- Principal Investigator Email
- paolo.ricchi@aocardarelli.it
- Contact Person Name
- Paolo Ricchi
- Contact Person Email
- paolo.ricchi@aocardarelli.it
- Site Name
- Azienda Socio Sanitaria Locale N. 8 Di Cagliari
- Department Name
- SC Microcitemie e Anemie Rare
- Principal Investigator Name
- Raffaella Origa
- Principal Investigator Email
- raffaella.origa@unica.it
- Contact Person Name
- Raffaella Origa
- Contact Person Email
- raffaella.origa@unica.it
- Site Name
- Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
- Department Name
- Attività Diurne Malattie Rare Internistiche - Medicina Generale
- Principal Investigator Name
- Elena Cassiniero
- Principal Investigator Email
- elena.cassinerio@policlinico.mi.it
- Contact Person Name
- Elena Cassiniero
- Contact Person Email
- elena.cassinerio@policlinico.mi.it
- Site Name
- University Hospital Of Ferrara
- Department Name
- Day Hospital della Talassemia e delle Emoglobinopatie
- Principal Investigator Name
- Filonema Longo
- Principal Investigator Email
- filomena.longo@ospfe.it
- Contact Person Name
- Filonema Longo
- Contact Person Email
- filomena.longo@ospfe.it
Netherlands
- Earliest CTIS Part Ii Submission Date
- 04-07-2024
- Latest Decision Or Authorization Date
- 29-10-2025
- Processing Time Days
- 482
- Number Of Sites
- 2
- Number Of Participants
- 4
Sites
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Department of Hematology, office Na 810
- 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
- Universitair Medisch Centrum Utrecht
- Department Name
- Hematology
- Principal Investigator Name
- Eduard van Beers
- Principal Investigator Email
- E.J.vanBeers-3@umcutrecht.nl
- Contact Person Name
- Eduard van Beers
- Contact Person Email
- E.J.vanBeers-3@umcutrecht.nl
Greece
- Earliest CTIS Part Ii Submission Date
- 04-07-2024
- Latest Decision Or Authorization Date
- 30-10-2025
- Processing Time Days
- 483
- Number Of Sites
- 4
- Number Of Participants
- 23
Sites
- Site Name
- Ippokratio General Hospital Of Thessaloniki
- Department Name
- Mediterranean Anemia Adult Unit,B' Pathology Clinic
- 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 Department, Unit of Mediterranean Anemia & Hemoglobinopathies
- Principal Investigator Name
- Alexandros Spryridonidis
- Principal Investigator Email
- spyridonidis@upatras.gr
- Contact Person Name
- Alexandros Spryridonidis
- Contact Person Email
- spyridonidis@upatras.gr
- Site Name
- Nosokomeio Paidon I Agia Sofia
- Department Name
- A’ Pediatric Clinic of NKUA, Unit of Mediterranean Anemia
- Principal Investigator Name
- Antonis Kattamis
- Principal Investigator Email
- ankatt@med.uoa.gr
- Contact Person Name
- Antonis Kattamis
- Contact Person Email
- ankatt@med.uoa.gr
- Site Name
- Laiko General Hospital Of Athens
- Department Name
- Center for Mediterranean Anemia
- Principal Investigator Name
- Maria Dimopoulou
- Principal Investigator Email
- mdimkma@gmail.com
- Contact Person Name
- Maria Dimopoulou
- Contact Person Email
- mdimkma@gmail.com
Spain
- Earliest CTIS Part Ii Submission Date
- 04-07-2024
- Latest Decision Or Authorization Date
- 26-01-2026
- Processing Time Days
- 571
- Number Of Sites
- 4
- Number Of Participants
- 15
Sites
- Site Name
- Hospital Universitario La Paz
- Department Name
- Hematology
- Principal Investigator Name
- Ana Mendoza Martínez
- Principal Investigator Email
- amendozam.externo@salud.madrid.org
- Contact Person Name
- Ana Mendoza Martínez
- Contact Person Email
- amendozam.externo@salud.madrid.org
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Hematology
- 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
- Site Name
- University Clinical Hospital Virgen De La Arrixaca
- Department Name
- Hematology
- Principal Investigator Name
- Eduardo Salido Fierrez
- Principal Investigator Email
- eduardoj.salido@carm.es
- Contact Person Name
- Eduardo Salido Fierrez
- Contact Person Email
- eduardoj.salido@carm.es
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Hematology
- Principal Investigator Name
- Salvador Payán-Pernía
- Principal Investigator Email
- sppayan@gmail.com
- Contact Person Name
- Salvador Payán-Pernía
- Contact Person Email
- sppayan@gmail.com
Sponsor
Primary sponsor
- Full Name
- Agios Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Fortrea Development Ltd. Branch Of Foreign Company
- Responsibilities
- CRO
Third parties
- {"country":"United States","full_name":"Intrinsic Lifesciences LLC","duties_or_roles":"Exploratory biomarkers","organisation_type":"Pharmaceutical company"}
- {"country":"Greece","full_name":"Fortrea Development Ltd. Branch Of Foreign Company","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Fortrea Development Limited","duties_or_roles":"IDMC","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"FCB Health New York","duties_or_roles":"Patient recruitment materials","organisation_type":"Industry"}
- {"country":"United States","full_name":"Medidata Solutions","duties_or_roles":"ePRO, eConsent","organisation_type":"Health care"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IVRS – treatment randomisation","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Lumanity Patient Centered Outcomes LLC","duties_or_roles":"Exit Interview","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"Targeted Genotyping","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Belgium","full_name":"AAC/Proximus","duties_or_roles":"24 Hour Medical support Coverage","organisation_type":"Industry"}
- {"country":"United States","full_name":"CPC","duties_or_roles":"6-minute Walk Test","organisation_type":"Industry"}
- {"country":"United States","full_name":"Firma Clinical Research","duties_or_roles":"Home health nursing","organisation_type":"Industry"}
- {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Pharma Services Limited","duties_or_roles":"Drug Depot/Investigational Product Supply","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"QPS LLC","duties_or_roles":"pharmacokinetics and pharmacodynamics","organisation_type":"Pharmaceutical company"}
- {"country":"Philippines","full_name":"Pharmaceutical Product Development","duties_or_roles":"","organisation_type":"Industry"}
Investigational products
- Investigational Product Name
- MITAPIVAT
- Active Substance
- MITAPIVAT
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL USE
- Authorisation Status
- Authorised
- Investigational Product Name
- Placebo for Mitapivat
- Modality
- Other
- Routes Of Administration
- ORAL USE
- Route
- ORAL USE
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