Key Inclusion Criteria: - Adult participant ≥ 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence for TD participants defined as ≥ 6 RBC units during the 24 weeks prior to randomization and no transfusion-free period for > 56 days during the 24 weeks prior to randomization. - Adult participant ≥ 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence for NTD participants defined as < 6 RBC units during the 24 weeks prior to randomization and, RBC transfusion-free during at least 8 weeks prior to randomization and, mean baseline Hb ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to randomization; hemoglobin values within 21 days post-transfusion will be excluded. - Adolescent participant 12 years to < 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence for TD participants defined as ≥ 4 RBC events during the 24 weeks prior to enrollment and, no transfusion-free period for > 56 days during the 24 weeks prior to enrollment. Participants must have a history of regular transfusions for at least 2 years. - Adolescent participant 12 years to < 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence for NTD participants defined as < 4 RBC events during the 24 weeks prior to enrollment and RBC transfusion-free during at least 8 weeks prior to enrollment and, mean baseline Hb ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to enrollment, hemoglobin values within 21 days post-transfusion will be excluded. - Adolescent participant has Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening. Key Exclusion Criteria: - Participants must not have a diagnosis of α-thalassemia Trait, Hb Bart hydrops, ATRx α-thalassemia, hemoglobin S/β-thalassemia, myelodysplasia subtype anemia, or with HbE homozygous beta gene mutation. - Participants must not have anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia, or any other hemolytic anemias. - Participants must not have bleeding disorders manifested by frequent bleeding episodes. - Participants must not have undergone episodes of hemolysis not related to alpha-thalassemia within the 8 weeks prior to randomization. - Participants must not have prior exposure to gene therapy to treat α-thalassemia. - Participants must not have undergone hematopoietic stem cell transplantation (HSCT) Note: Other protocol-defined inclusion/exclusion criteria apply.