An Open-label, Randomized, Phase 2, Parallel, Dose-Ranging, Multicenter Study of Sotatercept for the Treatment of Patients With Anemia and Low or Intermediate-1 Risk Myelodysplastic Syndromes or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 20
- 主要终点
- Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≤
- •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
排除标准
- •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
研究组 & 干预措施
Sotatercept 0.1 mg/kg
Sotatercept 0.1 mg/kg
干预措施: Sotatercept (Drug)
Sotatercept 0.5 mg/kg
Sotatercept 0.5 mg/kg
干预措施: Sotatercept (Drug)
Sotatercept 0.3 mg/kg
Sotatercept 0.3 mg/kg
干预措施: Sotatercept (Drug)
Sotatercept 1.0 mg/kg
Sotatercept 1.0 mg/kg
干预措施: Sotatercept (Drug)
Sotatercept 1.5 mg/kg
Sotatercept 1.5 mg/kg
干预措施: Sotatercept (Drug)
Sotatercept 2.0 mg/kg
Sotatercept 2.0 mg/kg
干预措施: Sotatercept (Drug)
结局指标
主要结局
Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)
时间窗: Day 2 to Day 142
The responder rate includes non-transfusion dependent efficacy (NTDE) participants and transfusion dependent efficacy (TDE) participants. For non-transfusion dependence efficacy (NTDE) participants who required \< 4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as an increase of \>=1.5 g/dL hemoglobin sustained for 56 days over a period of \>=8 weeks. For transfusion dependence efficacy (TDE) participants who required \>=4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as a decrease of \>= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks.
次要结局
- Time to Erythroid Hematological Improvement (HI-E) Response(Day 1 to Day 87)
- Duration of Erythroid Hematological Improvement (HI-E)(Day 1 to 183.7 weeks)
- Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression(Day 1 to 183.7 weeks)
- Kaplan-Meier Estimates for Progression-free Survival(Day 1 to 257.3 weeks)
- Kaplan-Meier Estimates for Overall Survival (OS)(Day 1 to 257.3 weeks)
- Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints(Cycle 1 Day 8 and !5 up to Cycle 2 Day 1)
- Participants With Treatment-Emergent Adverse Events (TEAE)(Day 1 up to 59.2 months)
- Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval(Day 2 to Day 142)
- Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression(Day 1 to 257.3 weeks)
- Dose Limiting Toxicities (DLTs)(Day 1 to 59.2 months)