A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT)

Inclusion Criteria: * Greater than or equal to (≥)18 years of age at the time of providing informed consent; * 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 deoxyribonucleic acid (DNA) analysis; * Considered transfusion-dependent, defined as 6 to 20 red blood cells (RBC) units transfused and ≤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; * Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle or agree to use two forms of contraception, one of which must be considered highly effective, from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can be an acceptable barrier method; * Written informed consent before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study. Exclusion Criteria: * Pregnant, breastfeeding, or parturient; * Documented history of homozygous or heterozygous sickle hemoglobin (Hb S) or hemoglobin C (Hb C); * Prior exposure to gene therapy or prior bone marrow or stem cell transplantation; * 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, 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 ≤6 months before providing informed consent; * Hepatobiliary disorders; * Estimated glomerular filtration rate \<45 milliliters per minute (mL/min)/1.73 meter (m)\^2 by Chronic Kidney Disease Epidemiology Collaboration creatinine equation; * Nonfasting triglycerides \>440 milligrams per deciliter (mg/dL) (5 millimoles per liter \[mmol/L\]); * Active infection requiring systemic antimicrobial therapy at the time of providing informed consent; * Positive test for hepatitis C virus antibody (HCVAb) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg); * Positive test for human immunodeficiency virus (HIV)-1 antibody (Ab) or HIV-2 Ab; * History of major surgery (including splenectomy) ≤6 months before providing informed consent and/or a major surgical procedure planned during the study; * Current enrollment or past participation (≤12 weeks before administration of the first dose of study drug or a timeframe equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational treatment or device; * Receiving strong 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 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, and magnesium stearate, Opadry® II Blue \[hypromellose, titanium dioxide, lactose monohydrate, triacetin, and Federal Food, Drug, and Cosmetic (FD\&C) Blue #2\]); * 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).