A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT)

NCT04770779 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: AG348-C-0182021-000212-342024-512747-23-00
• Study Type: interventional
• Target: 258
• Locations: 19 countries
• Sites: 75

Brief Summary

The primary objective of this study was to compare the effect of mitapivat versus placebo on transfusion burden in participants with α- or β-transfusion-dependent thalassemia.

Conditions

Transfusion-dependent Alpha-Thalassemia; Transfusion-dependent Beta-Thalassemia

Outcome Measures

Primary Outcomes (1)

• Double-blind Period: Percentage of Participants Who Achieved Transfusion Reduction Response (TRR)

  TRR is defined as ≥50% reduction in transfused red blood cells (RBC) units with a reduction of ≥2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline transfusion burden standardized to 12 weeks. Baseline transfusion burden standardized to 12 weeks= (12/24) × total number of RBC units transfused during 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 12 (Day 85) were considered nonresponders.

  Double-blind Period: Baseline through Week 48

Secondary Outcomes (19)

• Double-blind Period: Percentage of Participants Who Achieved TRR2

  Double-blind period: Baseline through Week 48

• Double-blind Period: Percentage of Participants Who Achieved TRR3

  Double-blind period: Baseline up to Week 13 through Week 48

• Double-blind Period: Percentage of Participants Who Achieved TRR4

  Double-blind period: Baseline up to Week 13 through Week 48

• Double-blind Period: Percent Change From Baseline in Transfused RBC Units

  Double-blind Period: Baseline, Week 13 through Week 48

• Double-blind Period: Percentage of Participants Who Achieved Transfusion-Independence

  Double-blind Period: Baseline through Week 48

Study Arms (2)

Mitapivat

EXPERIMENTAL

Participants randomized to receive mitapivat 100 milligrams (mg), orally, twice daily (BID) for 48 weeks in the double-blind (DB) period and for up to 5 years in the open label extension (OLE) period.

Drug: Mitapivat

Placebo

PLACEBO COMPARATOR

Participants randomized to receive placebo matching mitapivat, orally, BID for 48 weeks in the DB period followed by mitapivat 100 mg, orally, BID for up to 5 years in the OLE period.

Drug: Placebo Matching Mitapivat; Drug: Mitapivat

Interventions

Placebo Matching Mitapivat DRUG

Tablets

Placebo

Mitapivat DRUG

Tablets

Also known as: AG-348, AG-348 sulfate hydrate, Mitapivat sulfate

Mitapivat; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Greater than or equal to (≥)18 years of age at the time of providing informed consent;
• Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, hemoglobin E (HbE)/β-thalassemia, or α-thalassemia/hemoglobin H (HbH) disease) based on deoxyribonucleic acid (DNA) analysis;
• Considered transfusion-dependent, defined as 6 to 20 red blood cells (RBC) units transfused and ≤6-week transfusion-free period during the 24-week period before randomization;
• If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization;
• 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 two forms of contraception, one 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;
• Written informed consent before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study.

You may not qualify if:

• Pregnant, breastfeeding, or parturient;
• Documented history of homozygous or heterozygous sickle hemoglobin (Hb S) or hemoglobin C (Hb C);
• Prior exposure to gene therapy or prior bone marrow or stem cell transplantation;
• Currently receiving treatment with luspatercept; the last dose must have been administered ≥36 weeks before randomization;
• Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥36 weeks before randomization;
• 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;
• History of active and/or uncontrolled cardiac or pulmonary disease ≤6 months before providing informed consent;
• Hepatobiliary disorders;
• Estimated glomerular filtration rate \<45 milliliters per minute (mL/min)/1.73 meter (m)\^2 by Chronic Kidney Disease Epidemiology Collaboration creatinine equation;
• Nonfasting triglycerides \>440 milligrams per deciliter (mg/dL) (5 millimoles per liter \[mmol/L\]);
• Active infection requiring systemic antimicrobial therapy at the time of providing informed consent;
• Positive test for hepatitis C virus antibody (HCVAb) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg);
• Positive test for human immunodeficiency virus (HIV)-1 antibody (Ab) or HIV-2 Ab;
• History of major surgery (including splenectomy) ≤6 months before providing informed consent and/or a major surgical procedure planned during the study;
• Current enrollment or past participation (≤12 weeks before administration of the first dose of study drug or a timeframe equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational treatment or device;

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (75)

Phoenix Children's Hospital

Phoenix, Arizona, 85016-7710, United States

Location

San Diego Hospital, UC San Diego Health

La Jolla, California, 92093, United States

Location

Children's Hospital Oakland

Oakland, California, 94609-1809, United States

Location

Stanford Medicine

Palo Alto, California, 94304-1601, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201-2196, United States

Location

Weill Cornell Medical Center

New York, New York, 10065-4870, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710-3038, United States

Location

Penn Medicine - University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Cancer Care Alliance, University of Washington

Seattle, Washington, 98101, United States

Location

Hospital Das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP

Ribeirão Preto, 14051-260, Brazil

Location

GSH Banco de Sangue de São Paulo

São Paulo, 04006-002, Brazil

Location

MHAT "Dr. Nikola Vasiliev" AD

Kyustendil, 2500, Bulgaria

Location

UMHAT "Dr. Georgi Stranski" Pleven

Pleven, 5800, Bulgaria

Location

UMHAT "Sveti Georgi" EAD

Plovdiv, 4002, Bulgaria

Location

SHATHD Sofia

Sofia, 1756, Bulgaria

Location

UMHAT "Prof. Dr. Stoyan Kirkovich"

Stara Zagora, 6000, Bulgaria

Location

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Toronto General Hospital, University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Rigshospitalet

Hovedstaden, 2100, Denmark

Location

CHU Hôpital Henri Mondor

Créteil, 94010, France

Location

Hôpital Edouard Herriot, CHU de Lyon

Lyon, 69003, France

Location

CHU Hôpital de la Timone

Marseille, 13385, France

Location

Hôpital Necker Enfants Malades

Paris, 75015, France

Location

Charité - UB - CVK - Medizinische Klinik

Berlin, 13353, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

University General Hospital of Patras

Achaia, 26504, Greece

Location

Laiko General Hospital

Athens, 115 26, Greece

Location

Children's Hospital Agia Sophia, National and Kapodistrian University of Athens Medical School

Athens, 11527, Greece

Location

University Hospital of Ioannina

Ioannina, 455 00, Greece

Location

Ippokrateio General Hospital

Thessaloniki, 546 42, Greece

Location

Ospedale "A. Perrino" - Brindisi

Brindisi, 72100, Italy

Location

Ospedale Pediatrico Microcitemico

Cagliari, 09121, Italy

Location

Ospedale Sant'Anna

Ferrara, 44124, Italy

Location

Ente Ospedaliero Ospedali Galliera

Genova, 16128, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

A.O.U Di Modena

Modena, 41124, Italy

Location

AOU L. Vanvitelli Universita degli Studi della Campania Luigi Vanvitelli

Naples, 80138, Italy

Location

A.O.U. San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Chronic Care Center

Beirut, 9999, Lebanon

Location

Hospital Sultanah Bahiyah

Alor Star, 05460, Malaysia

Location

Hospital Sultanah Aminah Johor Bahru

Johor Bahru, 80100, Malaysia

Location

Hospital Queen Elizabeth, Kota Kinabalu

Kota Kinabalu, 88586, Malaysia

Location

Hospital Tunku Azizah

Kuala Lumpur, 50300, Malaysia

Location

Hospital Tengku Ampuan Afzan

Kuantan, 25100, Malaysia

Location

Hospital Umum Sarawak

Kuching, 93586, Malaysia

Location

Hospital Ampang

Pandan Indah, 68000, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, 10990, Malaysia

Location

Amsterdam Universitair Medisch Centrum, Locatie AMC

Amsterdam, 1105 AZ, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Erasmus MC

Westzeedijk 353, 3015 AA, Netherlands

Location

King Abdullah International Medical Research Center

Riyadh, 14611, Saudi Arabia

Location

King Khalid University Hospital

Riyadh, 90210, Saudi Arabia

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Phramongkutklao Hospital

Bangkok, 10400, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Faculty of Medicine Siriraj Hospital

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital, Khon Kaen University

Khon Kaen, 40000, Thailand

Location

Naresuan University Hospital

Mueang Phitsanulok, 65000, Thailand

Location

King Chulalongkorn Memorial Hospital

Pathum Wan, Thailand

Location

Acibadem Adana Hospital

Adana, 1130, Turkey (Türkiye)

Location

Akdeniz University Faculty of Medicine

Antalya, 07059, Turkey (Türkiye)

Location

Çukurova University

Balcalı, 01330, Turkey (Türkiye)

Location

Ege University Faculty of Medicine

Bornova, 35040, Turkey (Türkiye)

Location

Istanbul University Faculty of Medicine

Fatih, 34093, Turkey (Türkiye)

Location

Hacettepe University

Mersin, Turkey (Türkiye)

Location

Burjeel Medical City

Abu Dhabi, United Arab Emirates

Location

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

University College London

London, WC1E 6BT, United Kingdom

Location

MeSH Terms

Interventions

mitapivat

Results Point of Contact

• Title: Agios Medical Affairs
• Organization: Agios Pharmaceuticals, Inc.

medinfo@agios.com

833-228-8474

Study Officials

• Medical Affairs

  Agios Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: February 25, 2021
• Study Start: November 30, 2021
• Primary Completion: April 11, 2024
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 24, 2026
• Results First Posted: May 25, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); NL (3); TW (1); FR (4); CA (2); SA (2); MY (8); LE (1); US (10); IT (8); BR (2); GR (5); DE (3); GB (2); TH (7); BU (5); TU (6); ES (4); AE (1)