Recruiting
Phase 3

Mitapivat

Sponsor:

Agios Pharmaceuticals, Inc.

Code:

NCT07506863

Conditions

Transfusion-dependent Alpha-Thalassemia

Transfusion-dependent Beta-Thalassemia

Eligibility Criteria

Sex: All

Age: 1 - 17

Healthy Volunteers: Not accepted

Interventions

Mitapivat Matched Placebo

Mitapivat

Study Details

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

Study ID

NCT07506863

Start date

Sep, 2026

Status verified date

Sep, 2026

Completion date

Jun, 2032

Anticipated

Primary completion date

Jun, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 1 - 17

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Clinically symptomatic cholelithiasis or cholecystitis (prior cholecystectomy is not exclusionary).
  • 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.
  • Participants with known active hepatitis B or hepatitis C virus infection.
  • Participants with known human immunodeficiency virus (HIV) infection.
  • History of major surgery (including splenectomy) ≤ 6 months before providing informed consent/assent and/or a major surgical procedure planned during the study.
  • Current enrollment or past participation (within ≤12 weeks or a timeframe equivalent to 5 half-lives of the investigational study drug before administration of the first dose of study drug, whichever is longer) in any other clinical study involving an investigational treatment or device.
  • Receiving strong Cytochrome3A4/5 (CYP3A4/5) inhibitors that have not been stopped for ≥5 days or a timeframe equivalent to 5 half-lives (whichever is longer), or strong CYP3A4/5 inducers that have not been stopped for ≥4 weeks or a timeframe equivalent to 5 half-lives (whichever is longer), before randomization.
  • 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.
  • Known allergy, or other contraindication, to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and the Opadry filmcoat \[hypromellose, titanium dioxide, lactose monohydrate triacetin, and FD\&C Blue #2\]).
  • 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:

  • Participants who are institutionalized by regulatory or court order.
  • Participants 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).

Study Design

Enrollment

54 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Mitapivat

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.

placebo comparator: Placebo

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.

Interventions

Mitapivat Matched Placebo

Tablets or Granules

Mitapivat

Tablets or Granules

Primary outcome measure

  • Percentage of Participants Who Achieved Transfusion Reduction Response (TRR) Through Week 48 [ Time Frame: Baseline, through Week 48 ]

Central Contacts and Locations

Central contacts

Agios Medical Affairs

833-228-8474medinfo@agios.com

Locations

Emory-Children's Center/ Children's Healthcare of Atlanta: Arthur M. Blank Hospital

Recruiting

Atlanta, Georgia, United States, 30322

Weill Cornell Medical College/ New York Presbyterian

Recruiting

New York, New York, United States, 10065

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104-4318

University of Texas Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

More Information

Sponsor

Agios Pharmaceuticals, Inc.

Last update posted

Sep 28, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Agios Pharmaceuticals, Inc. on 2026-09-28. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.