Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)
Condition: Anemia; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Low to Intermediate-1 MDS; Myelodysplastic Syndromes (MDS); Chronic Myelomonocytic Leukemia (CMML)
MeSH terms: Leukemia; Preleukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Anemia; Myelodysplastic Syndromes; Syndrome
Intervention: Sotatercept
Intervention description: Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ACE-011; anemia; dose-ranging; intermediate-1 risk myelodysplastic syndromes; low risk myelodysplastic syndromes (MDS); multicenter; open-label; parallel; phase 2; randomized; Sotatercept; Non-proliferative chronic myelomonocytic leukemia (CMML); hemoglobin; transfusions

Summary:

      The primary objective of this study is to determine a safe, tolerable and effective dose of
      sotatercept that results in the greatest frequency of improvement of anemia in patients
      diagnosed with low- or intermediate-1 risk myelodysplastic syndromes (MDS) or
      non-proliferative chronic myelomonocytic leukemia (CMML).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women ≥ 18 years of age

          -  Documented diagnosis of myelodysplastic syndromes (MDS) or non-proliferative chronic
             myelomonocytic leukemia (CMML), white blood cells (WBC) ≤ 13,000 /mm^3, World Health
             Organization (WHO) that meets International Prognostic Scoring System (IPSS) criteria
             for low or intermediate-1 risk disease

          -  Anemia, Hemoglobin (Hgb) ≤ 9.0 g/dL or ≥ 2 units of Red Blood Cells (RBCs) within 84
             days

          -  No response or loss of response to Erythropoiesis-Stimulating Agents (ESAs) or
             erythropoetin (EPO) > 500 mU/ml

          -  Eastern Cooperative Group (ECOG) score ≤2.

          -  Creatinine < 1.5 * Upper Limit of the Normal (ULN)

          -  Total bilirubin ≤3.0 mg/dL

          -  Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) &
             Alanine Aminotransferase (ALT)/Serum Glutamic Pyruvic (SGPT) ≤3.0 * Upper Limit of
             Norma (ULN)

          -  Free of metastatic malignancy (other than MDS) for ≥2 years

          -  Highly effective methods of birth control for females and males

        Exclusion Criteria:

          -  Chromosome 5q deletion

          -  Pregnant or breast feeding women and males who do not agree to use condom during the
             sexual contact with females of childbearing potential

          -  Major surgery within 30 days

          -  Incomplete recovery or incomplete healing of wounds from previous surgery

          -  Heart failure ≥3 (New York Heart Association (NYHA))

          -  Thromboembolic or myocardial infarction event within 6 months

          -  Concurrent anti-cancer cytotoxic chemotherapy

          -  History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant
             protein

          -  Known positive for Human Immunovirus (HIV) or infectious Hepatitis type C or active
             infectious Hepatitis type B

          -  Clinically significant anemia unrelated to MDS

          -  Thrombocytopenia (<30,000/uL)

          -  Uncontrolled hypertension

          -  Treatment with another investigational drug or device within 28 days prior to Day 1

          -  Prior exposure to sotatercept (ACE-011)

          -  Any serious medical condition, lab abnormality or psychiatric illness