Study of Safety & PK of Luspatercept (ACE-536) in Pediatric Participants With Beta (β)-Thalassemia

Eligibility Criteria

• * Participant has a diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin H); β-thalassemia combined with α-thalassemia is allowed.
• * Participant has of active hepatitis C (HCV) infection, as demonstrated by a positive HCF-ribonucleic acid (RNS) test of sufficient sensitivity, or active infectious hepatitis B (as demonstrated by the presence of hepatitis B surface antigen (HBsAG) and/or hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) positive, or known positive human immunodeficiency virus (HIV).
• * Participant has deep vein thrombosis (DVT), stroke, or other thromboembolic event(s) (except clogged indwelling catheter) requiring medical intervention ≤ 24 weeks prior to enrollment.
• * Participant has platelet count \> 1000 x 109/L.
• * Participant has treatment with another investigational drug or device ≤ 28 days prior to enrollment.
• * Participant has prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
• * Participant underwent or is scheduled for HSCT or gene therapy.
• * Participant use of iron chelation therapy (ICT), if initiated ≤ 8 weeks prior to enrollment (allowed if initiated \> 8 weeks before or during treatment).
• * Participant received treatment with hydroxyurea immunomodulatory drugs IMiDs (such as thalidomide), other fetal Hb (HbF) inducers or erythropoiesis-stimulating agents (ESAs) ≤ 12 weeks prior to enrollment for NTD participants and ≤ 24 weeks for TD participants.
• * Participant is pregnant or breastfeeding female or plan to get pregnant during the study.
• * Participant has uncontrolled hypertension. Controlled hypertension for this protocol is considered: blood pressure value corresponding to ≤ Grade 1 according to NCI CTCAE version 5.0 with or without pharmacological treatment.
• * Participant has major organ damage, including:
• 1. Symptomatic splenomegaly
• 2. Liver disease with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \> 3X the upper limit of normal (ULN) for age
• 3. Heart disease, heart failure as classified by the New York Heart Association (NYHA) classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction within 6 months of enrollment
• 4. Lung disease, including pulmonary fibrosis or pulmonary hypertension of Grade ≥ 3 according to NCI-CTCAE version 5.0.
• 5. Renal insufficiency defined as:
• * A serum creatinine based on age/gender based on threshold derived from Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control.
• * Participant has proteinuria ≥ Grade 3 according to NCI CTCAE version 5.0 (which is equivalent to a urine protein/creatinine ratio \> 215 mg/mmol of creatinine), or a urine albumin/creatinine ratio \> 129 mg/mmol of creatinine.
• * Participant use of high dose long-term therapy with systemic glucocorticoids ≤ 12 weeks prior to enrollment (physiologic replacement therapy for adrenal insufficiency is allowed). Low-dose long-term (defined as ≤ 0.2 mg/kg/day or ≤ 10 mg/day of prednisone equivalent), short treatment (eg, for prevention or treatment of transfusion reactions) inhaled, intranasal and topical corticosteroids are allowed.
• * Participant has history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the IP (refer to the IB).
• * Participant use of cytotoxic agents, immunosuppressants ≤ 28 days prior to enrollment (ie, antithymocite globulin (ATG) or cyclosporine).
• * Participant has history of malignancy with the exception of:
• 1. Curatively resected nonmelanoma skin cancer.
• 2. Curatively treated carcinoma in situ.
• 3. Other solid tumor with no known active disease in the opinion of the Investigator.
• * Participant who has extramedullary hematopoiesis (EMH) complications or requires treatment to control the growth of EMH masse(s) during the screening period.
• * Participants with any medical or psychiatric condition that in the opinion of the investigator would put the participant at unacceptable risk of participating in the study or may impact interpretation of the study results.
• * Participants who use herbs or food supplements (eg: Chinese traditional medicine), if, per investigator's judgment, likely to impact the safety and efficacy assessment, for 24 weeks before initiating the study treatment for TD participants, and 12 weeks for NTD participants.