Phase 2 N=74 Randomized Treatment

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

Anemia · Myelodysplastic Syndromes · Chronic Myelomonocytic Leukemia · Low to Intermediate-1 MDS · Myelodysplastic Syndromes (MDS)

Bottom Line

View on ClinicalTrials.gov: NCT01736683 ↗

Enrolled (actual)

Serious AEs

28.4%

Results posted

Jun 2019

Primary outcome: Primary: Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate) — 0; 66.7; 42.9; 60.0 percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Sotatercept (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Merck Sharp & Dohme LLC
Primary completion: Apr 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)	0; 66.7; 42.9; 60.0; 40.0; 33.3	—
SECONDARY Time to Erythroid Hematological Improvement (HI-E) Response	24.0; 1.0; 1.0; 48; 1.0; 1.0	—
SECONDARY Duration of Erythroid Hematological Improvement (HI-E)	62.5; 104.0; 133.0; 96.0; 79.0; 1043.0	—
SECONDARY Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression	45.6; 78.0	—
SECONDARY Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression	15.1; 24.7; 67.4	—
SECONDARY Kaplan-Meier Estimates for Progression-free Survival	82.7; NA; NA; NA; NA	—
SECONDARY Kaplan-Meier Estimates for Overall Survival (OS)	82.7; NA; NA; NA; NA	—
SECONDARY Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints	288.06; 1426.00; 2237.46; 6525.37; 12886.14; 240.31	—
SECONDARY Participants With Treatment-Emergent Adverse Events (TEAE)	6; 4; 20; 34; 5; 2	—
SECONDARY Dose Limiting Toxicities (DLTs)	1; 1; 8; 19; 2; 0	—
SECONDARY Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval	0; 1; 3; 15; 1; 1	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01736683). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.