A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

• Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
• Documented diagnosis of MDS according to World Health Organization (WHO)/French American British (FAB) classification that meets IPSS R classification of very low, low, or intermediate risk disease, and:

Ring sideroblast ≥ 15% of erythroid precursors in bone marrow or ≥ 5% (but 200 U/L for subjects not previously treated with ESAs

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

• Prior therapy with disease modifying agents for underlying MDS disease.
• Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
• MDS associated with del 5q cytogenetic abnormality
• Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
• iron deficiency to be determined by serum ferritin less than or equal to 15 ug/L and additional testing if clinically indicated (eg, calculated transferrin saturation [iron/total iron binding capacity less than or equal to 20%] or bone marrow aspirate stain for iron).
• Prior allogeneic or autologous stem cell transplant
• Known history of diagnosis of acute myeloid leukemia (AML)
• Use of any of the following within 5 weeks prior to randomization:
• anticancer cytotoxic chemotherapeutic agent or treatment
• corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS
• iron-chelating agents, except for subjects on a stable or decreasing dose for at least 8 weeks prior to randomization
• other RBC hematopoietic growth factors (eg, Interleukin-3)
• investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to randomization or within 5 weeks, whichever is longer is excluded.
• Prior history of malignancies, other than MDS, 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)
• Major surgery within 8 weeks prior to randomization. Subjects must have completely recovered from any previous surgery prior to randomization