A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACE-031 (ActRIIB-IgG1) in Subjects With Duchenne Muscular Dystrophy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 24
- 试验地点
- 5
- 主要终点
- Number of Subjects With Adverse Reactions.
研究概览
简要总结
The purpose of this study is to determine if ACE-031 is safe and well-tolerated in boys with Duchenne Muscular Dystrophy (DMD) and to select the optimal doses of ACE-031 in terms of safety and pharmacodynamic (PD) activity for designing future studies. [Note: This study was terminated based on safety data]
详细描述
ACE-031, a soluble form of the human activin receptor type IIB, was administered once every 2 to 4 weeks by subcutaneous (SC) injection to boys with DMD. Dose levels and regimens for this multiple-dose study were based on data from the initial clinical studies in healthy subjects in which doses of 0.02 to 3 mg/kg SC were evaluated. A total of 24 subjects were enrolled into the study; 18 received ACE-031 and 6 placebo. All subjects were treated for a period of 12 weeks.The pharmacodynamic effects of ACE-031 treatment were assessed by a battery of motor function test that included the 6-Minute Walk Test, the 10-Minute Walk/Run Test, the 4-Stair Climb Test and the Gower Maneuver (GW). Muscle strength was assessed by hand-held myometry and fixed system testing. Body composition (i.e., spine BMD, lean mass, and fat mass) was assessed by whole body and lumbar spine DXA scans. Pulmonary function was assessed by forced vital capacity (FVC), maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). ACE-031 safety was evaluated through observation of the incidence and severity of adverse events.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of DMD confirmed
- •Corticosteroid therapy for at least one year prior to study day 1 and on a stable dose and schedule for at least 6 months prior to study day 1
- •Evidence of muscle weakness by clinical assessment
排除标准
- •Any previous treatment with another investigational product within 6 months prior to study day 1
- •Any clinically significant cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease that is not related to DMD
- •Inability to perform a whole body dual x-ray absorptiometry (DXA) scan
结局指标
主要结局
Number of Subjects With Adverse Reactions.
时间窗: From treatment initiation to End-of-Study Visit, approximately 24 weeks later
Number of subjects in each cohort with a treatment-emergent adverse event considered at least possibly related to study drug
Number of Subjects With Clinical Laboratory Adverse Reactions.
时间窗: Baseline to End-of-Study Visit, approximately 24 weeks later.
Number of subjects in each cohort with treatment-emergent adverse laboratory values judged to be at least possibly related to study drug
次要结局
- Percent Change in Total Lean Body Mass by DXA Scan.(Baseline to End-of-Study Visit, approximately 24 weeks later.)
- Change in Pulmonary Function Tests (FVC)(Baseline to End-of-Study Visit, approximately 24 weeks later.)
- Percent Change in Lumbar Spine Bone Mineral Density by DXA Scan.(Baseline to End-of-Study Visit, approximately 24 weeks later.)
- Percent Change in Muscle Strength Score by Hand-held Myometry.(Baseline to End-of-Study Visit, approximately 24 weeks later.)
- Change in Distance Traveled in 6 Minutes (Standardized 6-Minute-Walk Test).(Baseline to End-of-Study Visit, approximately 24 weeks later.)
- Change in Pulmonary Function Test (MIP)(Baseline to End-of-Study Visit. approximately 24 weeks)
- Change From Baseline in Time to Travel 10 Meters (Standardized 10-Meter-Walk/Run Test).(Baseline to End-of-Study Visit, approximately 24 weeks later.)
- Change in Pulmonary Function Test (MEP)(Baseline to End-of-Stuidy Visit, approximately 24 weeks)