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

Exclusion Criteria

• •The presence of any of the following will exclude a subject from enrollment:
• •1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• •2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• •3. Any condition that confounds the ability to interpret data from the study.
• •4. Diagnosis of hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg,Hemoglobin H).
• •5. Active hepatitis C (HCV) infection
• •6. Deep vein thrombosis (DVT) or stroke requiring medical intervention ≤ 24 weeks prior to randomization.
• •7. Subjects on chronic anticoagulant therapy are excluded, unless they stopped the treatment at least 28 days prior to randomization. Anticoagulant therapies for prophylaxis and for surgery or high-risk procedures as well as low molecular weight (LMW) heparin for superficial vein thrombosis (SVT) and chronic aspirin are allowed before and during the study.
• •8. Treatment with another investigational drug or device ≤ 28 days prior to randomization.
• •9. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
• •10. Platelet count \> 1000 x 109/L.
• •11. Subjects on iron chelation therapy (ICT) at the time of ICF signature must have initiated the treatment with ICT at least 24 weeks before the predicted randomization date. ICT can be initiated at any time during treatment and should be used according to the label.
• •12. Subject had Hydroxyurea and ESA treatment ≤ 24 weeks prior to randomization, and no prior gene therapy.
• •13. Subject is pregnant or a lactating female.
• •14. Uncontrolled hypertension. Controlled hypertension for this protocol is considered ≤ Grade 1 according to National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) version 4.0 (current active minor version).
• •15. Subject has major organ damage, including:
• •1. Liver disease with alanine aminotransferase (ALT) \> 3 x upper limit of normal (ULN) or history/evidence of cirrhosis, as well as presence of masses/tumor detected by ultrasound at screening.
• •2. 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 (MI) within 6 months of randomization.
• •3. Severe lung disease, including pulmonary fibrosis or pulmonary hypertension, ie, ≥G3 NCI CTCAE version 4.0 (current active minor version).
• •4. Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73 m2 (per Modification of Diet in Renal Disease \[MDRD\] formula).
• •16. Subject has received chronic systemic glucocorticoids ≤ 12 weeks prior to randomization (physiologic replacement therapy for adrenal insufficiency is allowed).
• •17. Major surgery ≤ 12 weeks prior to randomization (subjects must have completely recovered from any previous surgery prior to randomization).
• •18. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see Investigator Brochure).
• •19. Subject has received immunosuppressants ≤ 28 days prior to randomization.
• •20. History or current malignancies (solid tumors and hematological malignancies) unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed:
• •* Basal or squamous cell carcinoma of the skin
• •* Carcinoma in situ of the cervix
• •* Carcinoma in situ of the breast
• •* Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis \[TNM\] clinical staging system)