Mitapivat for children with thalassemia who need regular blood transfusions

Trial details

Who runs it

Agios Pharmaceuticals, Inc.

Trial code

NCT07506863EU 2025-524707-71-00

Record updated

29 October 2026

Original description

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.Read full original descriptionShow less

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Subjects With α- or β- Transfusion-Dependent Thalassemia

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.

Inclusion: 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: Prior exposure to gene therapy or prior bone marrow or stem cell transplantation, including any prior exposure to myeloablative chemotherapy; 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; 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; 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; 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); Any conditions other than thalassemia expected to affect sexual maturation; Participants with known active hepatitis B or hepatitis C virus infection; Participants with known human immunodeficiency virus (HIV) infection; Documented history of homozygous or heterozygous hemoglobin S (HbS) or hemoglobin C (HbC); 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); Nonfasting triglycerides >215 milligrams per deciliter (mg/dL) [5 millimole per liter (mmol/L)]; 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]); 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; Pregnant or breastfeeding; Renal dysfunction as defined by an estimated glomerular filtration rate <60 milliliters per minute (mL/min)/1.73-meter square (m\^2).

ClinicalTrials.gov NCT07506863 · EU CTIS 2025-524707-71-00