Clinical trial • Phase III • Haematology

MITAPIVAT for Transfusion-dependent alpha thalassemia | Transfusion-dependent beta thalassemia

Phase III trial of MITAPIVAT for Transfusion-dependent alpha thalassemia | Transfusion-dependent beta thalassemia.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Transfusion-dependent alpha thalassemia | Transfusion-dependent beta thalassemia
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
03-07-2024
First CTIS Authorization Date
30-07-2024

Trial design

Randomised, placebo for mitapivat (placebo comparator; dose/schedule not specified)-controlled Phase III trial in Greece, Bulgaria, Denmark and others.

Randomised
Yes
Comparator
Placebo for Mitapivat (placebo comparator; dose/schedule not specified)
Target Sample Size
76
Trial Duration For Participant
336

Eligibility

Recruits 76 Vulnerable population flag selected. The protocol excludes institutionalized subjects or those in situations that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor). Written informed consent is required from participants (no assent provisions described, as minimum age is ≥18)..

Pregnancy Exclusion
Pregnant, breastfeeding, or parturient.
Vulnerable Population
Vulnerable population flag selected. The protocol excludes institutionalized subjects or those in situations that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor). Written informed consent is required from participants (no assent provisions described, as minimum age is ≥18).

Inclusion criteria

  • {"criterion_text":"- ≥18 years of age at the time of providing informed consent.\n- Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, HbE/β-thalassemia, or α-thalassemia/HbH disease) based on DNA analysis from the subject’s medical record. If this information is not available from the subject’s medical record, DNA analysis can be performed by a local laboratory during the Screening Period. If a local laboratory is unable to perform the test, results from the comprehensive α- and β-globin genotyping performed by the study central laboratory can be used.\n- Transfusion dependent, defined as 6 to 20 RBC units transfused and a ≤6-week transfusion-free period during the 24-week period before randomization.\n- If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization.\n- Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may induce 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.\n- 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.\n- Nonfasting triglycerides >440 mg/dL (5 mmol/L).\n- 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.\n- Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen.\n- Positive test for HIV-1 Ab or HIV-2 Ab.\n- History of major surgery (including splenectomy) ≤6 months before providing informed consent and/or a major surgical procedure planned during the study.\n- 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 treatment, whichever is longer) in any other clinical study involving an investigational treatment or device.\n- 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.\n- 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 ≥12 weeks before randomization.\n- 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]).\n- 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).\n- Documented history of homozygous or heterozygous HbS or HbC.\n- Prior exposure to gene therapy or prior bone marrow or stem cell transplantation.\n- Currently receiving treatment with luspatercept; the last dose must have been administered ≥36 weeks before randomization.\n- Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥36 weeks before randomization.\n- 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.\n- 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.\n- 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).\n- Estimated glomerular filtration rate <45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration creatinine equation."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Transfusion reduction response (TRR), defined as a ≥50% reduction in transfused red blood cell (RBC) units with a reduction of ≥2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline","definition_or_measurement_approach":"TRR is measured as a ≥50% reduction in transfused RBC units with a reduction of ≥2 RBC units in any consecutive 12-week period through Week 48 compared with baseline."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
76
Recruitment Window Months
95
Consent Approach
Written informed consent is required before any study-related procedures; informed consent forms and subject information sheets are available in multiple languages (documents available in English, Greek, Bulgarian, Dutch, Spanish, French, German, Arabic, Italian among others). No assent process is described (minimum age ≥18).

Geography

Total Number Of Sites
30
Total Number Of Participants
128

Greece

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
30-10-2025
Processing Time Days
472
Number Of Sites
4
Number Of Participants
19

Sites

Site Name
Laiko General Hospital Of Athens
Department Name
Center for Mediterranean Anemia
Contact Person Name
Maria Dimopoulou
Contact Person Email
mdimkma@gmail.com
Site Name
Nosokomeio Paidon I Agia Sofia
Department Name
A’ Pediatric Clinic of NKUA, Unit of Mediterranean Anemia
Contact Person Name
Antonis Kattamis
Contact Person Email
ankatt@med.uoa.gr
Site Name
Ippokratio General Hospital Of Thessaloniki
Department Name
Mediterranean Anemia Adult Unit,B' Pathology Clinic
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
Contact Person Name
Alexandros Spryridonidis
Contact Person Email
spyridonidis@upatras.gr

Bulgaria

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
03-11-2025
Processing Time Days
476
Number Of Sites
5
Number Of Participants
34

Sites

Site Name
Multiprofile Hospital For Active Treatment Dr Nikola Vasiliev AD
Department Name
Department of Transfusion Hematology
Contact Person Name
Desislava Ilieva-Chiviyska
Site Name
National Specialised Hospital For Active Treatment Of Haematological Diseases
Department Name
Department of Hematopoietic Stem Cell Transplantation
Contact Person Name
Penka Ganeva
Contact Person Email
ganevapenka@yahoo.com
Site Name
University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD
Department Name
Clinic of Clinical Hematology
Contact Person Name
Lachezar Bogdanov
Contact Person Email
bogdanov71@gmail.com
Site Name
University Multiprofile Hospital For Active Treatment Saint Georgi EAD
Department Name
Department of Clinical Hematology
Contact Person Name
Pencho Georgiev
Contact Person Email
penchogeorgiev@yahoo.com
Site Name
Umbal - Prof. D-R Stoyan Kirkovich AD
Department Name
Department of Clinical Hematology
Contact Person Name
Mariya Todorova
Contact Person Email
dr.maria.dtodorova@gmail.com

Denmark

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
28-10-2025
Processing Time Days
470
Number Of Sites
1
Number Of Participants
8

Sites

Site Name
Rigshospitalet
Department Name
Department of Heamatology
Contact Person Name
Andreas Glenthøj
Contact Person Email
andreas.glenthoej@regionh.dk

Italy

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
29-10-2025
Processing Time Days
471
Number Of Sites
6
Number Of Participants
14

Sites

Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
DAI Materno Infantile
Contact Person Name
Silverio Perrotta
Site Name
Ente Ospedaliero Ospedali Galliera Di Genova
Department Name
S.S.D. Microcitemia Anemie Congenite e Dismetabolismo del ferro
Contact Person Name
Manuela Balocco
Contact Person Email
manuela.balocco@galliera.it
Site Name
Azienda Ospedaliero Universitaria Di Modena
Department Name
Medicina Interna
Contact Person Name
Francesca Ferrara
Contact Person Email
ferrara.francesca@aou.mo.it
Site Name
Azienda Sanitaria Locale Br
Department Name
U.O.C di Ematologia
Contact Person Name
Domenico Pastore
Contact Person Email
domenico.pastore0@gmail.com
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Attività Diurne Malattie Rare Internistiche - Medicina Generale
Contact Person Name
Elena Cassiniero
Site Name
Azienda Socio Sanitaria Locale N. 8 Di Cagliari
Department Name
SC Microcitemie e Anemie Rare
Contact Person Name
Raffaella Origa
Contact Person Email
raffaella.origa@unica.it

Germany

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
29-10-2025
Processing Time Days
471
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
Universitaet Leipzig
Department Name
Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie
Contact Person Name
Carmen Herling
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Hämatologie und Stammzelltransplantation
Contact Person Name
Ferras Alashkar
Contact Person Email
alexander.roeth@uk-essen.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Med. Kl. m. S. Hämatologie, Onkologie und Tumorimmunologie
Contact Person Name
Michaela Schwarz
Contact Person Email
michaela.schwarz@charite.de

France

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
30-10-2025
Processing Time Days
472
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Hospices Civils De Lyon
Department Name
Hematology
Contact Person Name
Giovanna Cannas
Contact Person Email
giovanna.cannas@chu-lyon.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Hematology
Contact Person Name
Jean Mignard
Contact Person Email
estelle.jean@ap-hm.fr
Site Name
Hopital Necker Enfants Malades
Department Name
Hematology
Contact Person Name
Laure Joseph
Contact Person Email
laure.joseph@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Hematology
Contact Person Name
Pablo Bartolucci
Contact Person Email
pablo.bartolucci@aphp.fr

Netherlands

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
29-10-2025
Processing Time Days
471
Number Of Sites
3
Number Of Participants
12

Sites

Site Name
Universitair Medisch Centrum Utrecht
Department Name
Hematology
Contact Person Name
Eduard van Beers
Contact Person Email
E.J.vanBeers-3@umcutrecht.nl
Site Name
Academisch Medisch Centrum
Department Name
Department of Hematology
Contact Person Name
Barend Jacob Biemond
Contact Person Email
b.j.biemond@amc.uva.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Department of Hematology, office Na 810
Contact Person Name
Anita Rijneveld
Contact Person Email
a.rijneveld@erasmusmc.nl

Spain

Earliest CTIS Part Ii Submission Date
15-07-2024
Latest Decision Or Authorization Date
26-01-2026
Processing Time Days
560
Number Of Sites
4
Number Of Participants
17

Sites

Site Name
Hospital Universitari Vall D Hebron
Department Name
Hematology
Contact Person Name
David Beneitez Pastor
Contact Person Email
david.beneitez@vallhebron.cat
Site Name
Hospital Universitario La Paz
Department Name
Hematology
Contact Person Name
Ana Mendoza Martinez
Site Name
University Clinical Hospital Virgen De La Arrixaca
Department Name
Hematology
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
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 (sponsor duties include codes 1,12,15 (value CRO),2,8)

Third parties

  • {"country":"Greece","full_name":"Fortrea Development Ltd. Branch Of Foreign Company","duties_or_roles":"Codes: 1,12,15 (value: CRO),2,8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"ePRO, eConsent; other duties (code 7)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"Targeted genotyping","organisation_type":"Laboratory/Research/Testing facility"}
  • {"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 Kingdom","full_name":"Fortrea Development Limited","duties_or_roles":"IDMC; other sponsor duties (codes: 2,8)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"QPS LLC","duties_or_roles":"pharmacokinetics and pharmacodynamics","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Philippines","full_name":"Pharmaceutical Product Development","duties_or_roles":"Codes: 6,8","organisation_type":"Industry"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Central laboratory functions (code 4)","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":"Endpoint Clinical Inc.","duties_or_roles":"IVRS – treatment randomisation","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Intrinsic Lifesciences LLC","duties_or_roles":"Exploratory biomarkers","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"AAC/Proximus","duties_or_roles":"24 Hour Medical support Coverage","organisation_type":"Industry"}

Investigational products

Investigational Product Name
MITAPIVAT
Active Substance
MITAPIVAT
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised (prodAuthStatus=1)
Investigational Product Name
Placebo for Mitapivat
Modality
Other
Authorisation Status
Not authorised / N/A

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