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

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).