A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With α- or β-Non-Transfusion-Dependent Thalassemia

Official title

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-Non-Transfusion-Dependent Thalassemia

Overview

The primary objective of this study is to compare the effect of mitapivat versus placebo on anemia in pediatric participants with alpha- or beta-non-transfusion-dependent thalassemia.

Interventions

• Drug Mitapivat
  Tablets or Granules
• Drug Placebo Matching Mitapivat
  Tablets or Granules

Primary outcome measures

• Percentage of Participants Who Achieved a Hemoglobin (Hb) Response [Time frame: Baseline, Week 12 through Week 24]

Secondary outcome measures (12)

• Change From Baseline in Average Hb Concentration From Week 12 Through Week 24 [Time frame: Baseline, Week 12 through Week 24]
• Percentage of Participants Who Achieved a Hb 1.5+ Response [Time frame: Baseline, Week 12 through Week 24]
• Change From Baseline in Indirect Bilirubin at Week 24 [Time frame: Baseline, Week 24]
• Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24 [Time frame: Baseline, Week 24]
• Change From Baseline in Haptoglobin at Week 24 [Time frame: Baseline, Week 24]
• Change From Baseline in Reticulocytes at Week 24 [Time frame: Baseline, Week 24]
• Change From Baseline in Erythropoietin at Week 24 [Time frame: Baseline, Week 24]
• Cohort 1: Change From Baseline in Estradiol Through Week 24 [Time frame: Baseline, up to Week 24]
• Cohort 1: Change From Baseline in Estrone Through Week 24 [Time frame: Baseline, up to Week 24]
• Cohort 1: Change From Baseline in Total Testosterone Through Week 24 [Time frame: Baseline, through Week 24]
• Cohort 1: Change From Baseline in Free Testosterone Through Week 24 [Time frame: Baseline, through Week 24]
• Cohort 1: Change From Baseline in Luteinizing Hormone Through Week 24 [Time frame: Baseline, through Week 24]

Eligibility criteria

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.
• Hb concentration ≤10.0 grams per deciliter (g/dL) \[100.0 grams per liter (g/L)\], based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period.
• Non-transfusion dependent, defined as ≤5 transfusion episodes (also referred to as "transfusion events") during the 24-week period before randomization and no red blood cells (RBC) transfusions ≤8 weeks before providing informed consent/assent and no RBC transfusions during the Screening Period.
• 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 ≥18 weeks before randomization.
• Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥18 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) ≤16 weeks 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Texas Southwestern Medical Center — Dallas

Identifiers

NCT: NCT07517133 · AG348-C-028 · 2025-524706-15-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗