A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT)

NCT07506863 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: AG348-C-0292025-524707-71-00
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Transfusion Reduction Response (TRR) Through Week 48

  TRR is defined as ≥50 percent (%) reduction in transfused red blood cells (RBC) volume (normalized by weight) in any consecutive 12-week period through Week 48 compared with historical RBC transfusion volume (normalized by weight) and standardized to 12 weeks.

  Baseline, through Week 48

Secondary Outcomes (26)

• Percentage of Participants Who Achieved TRR2 From Week 13 to Week 24

  Baseline, Week 13 through Week 24

• Percentage of Participants Who Achieved TRR3 From Week 25 to Week 36

  Baseline, Week 25 through Week 36

• Percentage of Participants Who Achieved TRR4 From Week 37 to Week 48

  Baseline, Week 37 through Week 48

• Percentage of Participants Who Achieved TRR5 From Week 25 to Week 48

  Baseline, Week 25 through Week 48

• Percent Change in Transfused RBC Volume (Normalized by Weight) From Week 13 Through Week 48 Compared With Historical Transfusion Volume (Normalized by Weight) and Standardized to 36 Weeks

  Baseline, Week 13 through Week 48

Study Arms (2)

Mitapivat

EXPERIMENTAL

Participants will receive oral mitapivat twice daily (BID), with dose determined by age and weight, for 48 weeks during the double blind (DB) period. Enrollment is conducted sequentially by age cohort, beginning with the oldest cohort. Cohort 1: 12 to \<18 years Cohort 2: 6 to \<12 years Cohort 3: 1 to \<6 years Participants who complete the DB period may continue receiving mitapivat in the open label extension (OLE) period for up to 144 weeks.

Drug: Mitapivat

Placebo

PLACEBO COMPARATOR

Participants will receive oral placebo matching mitapivat, administered BID, with dosing based on age and weight, for 48 weeks during the DB period. Enrollment is conducted sequentially by age cohort, beginning with the oldest cohort. Cohort 1: 12 to \<18 years Cohort 2: 6 to \<12 years Cohort 3: 1 to \<6 years Participants who complete the DB period may transition to receive mitapivat in the OLE period for up to 144 weeks.

Drug: Mitapivat Matched Placebo; Drug: Mitapivat

Interventions

Mitapivat Matched Placebo DRUG

Tablets or Granules

Placebo

Mitapivat DRUG

Tablets or Granules

Also known as: AG-348, Mitapivat sulfate

Mitapivat; Placebo

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Written informed consent/assent from the participant (or their legally authorized representative, parent(s), or legal guardian) must be obtained before any study-related procedures are conducted and participants must be willing to comply with all study procedures for the duration of the study.
• Aged 1 to \<18 years and weighing at least 7 kilograms (kg) at the time of providing informed consent/assent.
• 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 Hemoglobin (Hb) electrophoresis, Hb high-performance liquid chromatography, and/or DNA analysis from the participant's medical record. If this information is not available from the participant'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.
• Transfusion dependent, defined as 6 to 20 transfusion episodes (also referred to as "transfusion events") and a ≤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.
• Female participants who have attained menarche 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 informed consent/assent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can include an acceptable barrier method.

You may not qualify if:

• Pregnant or breastfeeding.
• Documented history of homozygous or heterozygous hemoglobin S (HbS) or hemoglobin C (HbC).
• Prior exposure to gene therapy or prior bone marrow or stem cell transplantation, including any prior exposure to myeloablative chemotherapy.
• Any conditions other than thalassemia expected to affect sexual maturation.
• 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/assent, 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 or clinically relevant QT prolongation within 6 months before providing informed consent/assent.
• Hepatobiliary disorders, including but not limited to:
• Liver disease with histopathological evidence or clinical diagnosis of cirrhosis or severe fibrosis.
• History of drug-induced cholestatic hepatitis.
• Aspartate Aminotransferase (AST) \>2.5\*Upper Limit of Normal (ULN) (unless due to hemolysis and hepatic iron deposition) and Alanine Transaminase (ALT) \>2.5\*ULN (unless due to hepatic iron deposition).
• Renal dysfunction as defined by an estimated glomerular filtration rate \<60 milliliters per minute (mL/min)/1.73-meter square (m\^2).
• Nonfasting triglycerides \>215 milligrams per deciliter (mg/dL) \[5 millimole per liter (mmol/L)\].
• Active infection requiring systemic antimicrobial therapy at the time of providing informed consent/assent. 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.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

MeSH Terms

Interventions

mitapivat

Central Study Contacts

Agios Medical Affairs

CONTACT

833-228-8474; medinfo@agios.com

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: March 26, 2026
• First Posted: April 2, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2032
• Last Updated: June 23, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share