A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion Dependent Alpha- or Beta-Thalassemia (a- or ß-NTDT)

INTERVENTION: subjects will be randomly assigned in a 2:1 ratio to receive study drug (mitapivat or placebo, respectively) The study will include approximately 171 adult and adolescent participants (= 18 years of age) with NTDT. Subjects will receive 100 mg twice‐daily mitapivat or matched‐placebo for oral administration. Eligible subjects will be randomly assigned in a 2:1 ratio to receive study drug (mitapivat or placebo, respectively) Randomization will be stratified by baseline Hb concentration (=9.0 g/dL or 9.1‐10.0 g/dL) and by thalassemia genotype. Study subjects, Investigators, clinical study center personnel, pharmacists, and the Sponsor will be blinded to the subject’s treatment assignment. During the Double‐blind Period, an unblinded Independent Data Monitoring Committee will be responsible for ongoing monitoring of the safety of subjects. Treatment CONDITION: Patients with a diagnosis of NTDT thalassemia (ß‐thalassemia with or without a‐globin gene mutations, HbE/ß‐thalassemia, or a‐thalassemia/HbH disease). 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 or during the Screening Period. ; Thalassemia beta‐Thalassemia alpha‐Thalassemia Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Thalassemia beta‐Thalassemia alpha‐Thalassemia Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases PRIMARY OUTCOME: Name: Effect of mitapivat versus placebo on anemia (Hemoglobin (Hb) response);Timepoints: from Week 12 through Week 24 compared with baseline;Measure: =1.0 g/dL increase in average Hb concentration SECONDARY OUTCOME: Name: Effect of mitapivat versus placebo on fatigue;Timepoints: Change from baseline from Week 12 through Week 24;Measure: average Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐Fatigue) subscale score Name: Effect of mitapivat versus placebo on additional measures of anemia;Timepoints: Change from baseline from Week 12 through Week 24;Measure: average Hb concentration INCLUSION CRITERIA: 1. =18 years of age at the time of providing informed consent. 2. Documented diagnosis of thalassemia (ß‐thalassemia with or without a‐globin gene mutations, HbE/ß‐thalassemia, or a‐thalassemia/HbH disease) based on Hb electrophoresis, Hb high‐performance liquid chromatography, and/or DNA analysis from the subject’s medical record. If this information is not available from the subject’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 a‐ and ß‐globin genotyping performed by the study central laboratory can be used. 3. Hb concentration =10.0 g/dL, based on an average of at least 2 Hb concentration measurements (separated by =7 days) collected during the Screening Period. 4. Non–transfusion dependent, defined as =5 red blood cell (RBC) units during the 24‐week period before randomization, and no RBC transfusio