Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Anemia; Chronic Myelomonocytic Leukemia (CMML); Myelodysplastic Syndromes (MDS); Low to Intermediate-1 MDS; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia

Treatments: Drug: Sotatercept

Study type: Interventional

Funder types: Industry

Identifiers

NCT01736683

7962-017

2012-002601-22 (EudraCT Number)

ACE-011-MDS-001

Details and patient eligibility

About

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).

Enrollment: 74 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

74 participants in 6 patient groups

Sotatercept 0.1 mg/kg

Experimental group

Description:

Sotatercept 0.1 mg/kg

Treatment:

Drug: Sotatercept

Sotatercept 0.3 mg/kg

Experimental group

Description:

Sotatercept 0.3 mg/kg

Treatment:

Drug: Sotatercept

Sotatercept 0.5 mg/kg

Experimental group

Description:

Sotatercept 0.5 mg/kg

Treatment:

Drug: Sotatercept

Sotatercept 1.0 mg/kg

Experimental group

Description:

Sotatercept 1.0 mg/kg

Treatment:

Drug: Sotatercept

Sotatercept 1.5 mg/kg

Experimental group

Description:

Sotatercept 1.5 mg/kg

Treatment:

Drug: Sotatercept

Sotatercept 2.0 mg/kg

Experimental group

Description:

Sotatercept 2.0 mg/kg

Treatment:

Drug: Sotatercept