Inclusion Criteria:

   - 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 Hb electrophoresis, Hb high-performance liquid chromatography
   (HPLC)), and/or deoxyribonucleic acid (DNA) analysis;

   - 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 red blood cell (RBC) units during the 24-week
   period before randomization; and no RBC transfusions ≤8 weeks before providing
   informed consent and no RBC transfusions during the Screening Period;

   - If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before
   randomization;

   - Women of child-bearing potential (WOCBP) must be abstinent of sexual activities that
   may result in pregnancy as part of their usual lifestyle or agree to use 2 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 (HbS) or hemoglobin
   C (HbC);

   - 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 ≥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;

   - History of active and/or uncontrolled cardiac or pulmonary disease ≤6 months before
   providing informed consent, except for nonmelanomatous skin cancer in situ, cervical
   carcinoma in situ, or breast carcinoma in situ;

   - Hepatobiliary disorders;

   - Estimated glomerular filtration rate <45 milliliters per minute (mL/min)/1.73 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) ≤16 weeks 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 ≥10 weeks before randomization;

   - Known allergy 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
   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)