Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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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]

Detailed Description
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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.

Official Title
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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

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Biological: ACE-031 0.5 mg/kg q4wk
* Biological: ACE-031 1.0 mg/kg q2wk
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of DMD confirmed Ambulant 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 4 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACE-031 0.5 mg/kg q4wk<br> | Biological: ACE-031 0.5 mg/kg q4wk<br>* ACE-031 0.5 mg/kg subcutaneously once every 4 weeks for 12 weeks.<br>|
| Experimental: ACE-031 1.0 mg/kg q2wk<br> | Biological: ACE-031 1.0 mg/kg q2wk<br>* ACE-031 1.0 mg/kg subcutaneously once every 2 weeks for 12 weeks.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Adverse Reactions. | Number of subjects in each cohort with a treatment-emergent adverse event considered at least possibly related to study drug | From treatment initiation to End-of-Study Visit, approximately 24 weeks later | 
| Number of Subjects With Clinical Laboratory Adverse Reactions. | Number of subjects in each cohort with treatment-emergent adverse laboratory values judged to be at least possibly related to study drug | Baseline to End-of-Study Visit, approximately 24 weeks later. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Total Lean Body Mass by DXA Scan. |  | 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. | Manual Muscle Testing (MMT) is a procedure to measure the function and strength of individual muscles and muscle groups. Hand-held myometry, using a device known as a dynamometer, is one method used for MMT. The dynamometer is held against the patient's limb by the examiner and the patient is asked to resist the force applied by the examiner. The dynamometer measures the force applied by the patient, providing a quantitative and objective assessment of strength of the particular muscle or muscle group. The effectiveness of a therapeutic intervention on muscle strength, as measured by hand-held myometry, can be assessed by comparing post-treatment to pre-treatment (baseline) measurements. | Baseline to End-of-Study Visit, approximately 24 weeks later. | 
| Change in Distance Traveled in 6 Minutes (Standardized 6-Minute-Walk Test). | Change in distance traveled in 6 minutes (standardized 6-Minute-Walk Test); stratified by baseline age (<10 years vs. >=10 years) | Baseline to End-of-Study Visit, approximately 24 weeks later. | 
| 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 Tests (FVC) | Forced Vital Capacity (FVC); 1 of 3 separate tests employed to assess pulmonary function in this study | Baseline to End-of-Study Visit, approximately 24 weeks later. | 
| Change in Pulmonary Function Test (MIP) | Maximum Inspiratory Pressure (MIP); 2 of 3 separate tests employed to assess pulmonary function in this study | Baseline to End-of-Study Visit. approximately 24 weeks | 
| Change in Pulmonary Function Test (MEP) | Maximum Expiratory Pressure (MEP); 3 of 3 separate tests employed to assess pulmonary function in this study | Baseline to End-of-Stuidy Visit, approximately 24 weeks |