A Study to Determine the Efficacy and Safety of Luspatercept in Adults With Non Transfusion Dependent Beta (β)-Thalassemia

The primary objective is: \- To evaluate the effect of luspatercept (BMS-986346) versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval, from Week 13 to Week 24, compared to baseline. The secondary objectives are: * To evaluate the effect of luspatercept versus placebo in anemia-related symptoms in participants with β-thalassemia, as measured by non-transfusion dependent β-thalassemia-patient reported outcome (NTDT-PRO) over continuous 12-week intervals (from Weeks 13 to 24 and from Weeks 37 to 48) compared to baseline. * To evaluate the effect of luspatercept versus placebo on functional and health-related quality of life (QoL) as measured by Medical Outcomes Study 36-Item Short Form (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaires * To evaluate the long-term effect of luspatercept versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval from Week 37 to Week 48, compared to baseline * To evaluate the effect of luspatercept versus placebo on iron overload, as measured by liver iron concentration (LIC) and iron chelation therapy (ICT) daily dose * To evaluate the effect of luspatercept versus placebo on iron overload, as measured by serum ferritin * To evaluate the duration of erythroid response * To evaluate the effect of luspatercept versus placebo on physical activity measured by 6-minute walk test (6MWT) Safety and Pharmacokinetics (PK) Objectives * To evaluate safety and tolerability of luspatercept, including immunogenicity * To evaluate population pharmacokinetics (PK) of luspatercept in subjects with β-thalassemia The exploratory objectives are: * To evaluate the effect of luspatercept versus placebo on measures of extra-medullary hematopoietic (EMH) masses, bone mineral density, splenomegaly, pulmonary hypertension, and leg ulcers, when present * To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the NTDT severity score system * To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the Morbidity-free Survival parameters * To examine the relationship of baseline and change in serum Growth Differentiation Factor 11 (GDF11) and other related biomarkers with response to treatment with luspatercept * To examine the effect of luspatercept on fetal hemoglobin (HbF) * To examine the effect of luspatercept on Health Resource Utilization (HRU)