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Based on preliminary safety data.
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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]
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ACE-031 0.5 mg/kg q4wk | Experimental |
| |
| ACE-031 1.0 mg/kg q2wk | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACE-031 0.5 mg/kg q4wk | Biological | ACE-031 0.5 mg/kg subcutaneously once every 4 weeks for 12 weeks. |
|
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Acceleron Investigative Site | Calgary | Alberta | Canada | |||
| Acceleron Investigative Site |
Abstract summarizing trial data has been published online in Muscle & Nerve 23-Dec-2016 https://www.ncbi.nlm.nih.gov/pubmed/27462804 The Sponor currently has no plans to make IPD available for a number of reasons; (i) the study was terminated by the Sponsor prematurely based upon concerns for potential adverse drug reactions following long-term use, which were identified in chronic toxicity studies in animals, (ii) the study population was one with a rare disease, in a groups of subjects with a relatively narrow age range, across a small number of study sites. The Sponsor believes that these factors, taken together, make patient anonymity a significant challenge.
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| ID | Title | Description |
|---|---|---|
| FG000 | ACE-031 0.5 mg/kg q4wk | ACE-031 0.5 mg/kg q4wk: ACE-031 0.5 mg/kg subcutaneously once every 4 weeks for 12 weeks. |
| FG001 | ACE-031 1.0 mg/kg q2wk | ACE-031 1.0 mg/kg q2wk: ACE-031 1.0 mg/kg subcutaneously once every 2 weeks for 12 weeks. |
| FG002 | ACE-031 ACE-03 2.5 mg/kg q4wk | ACE-031 2.5 mg/kg q4wk: ACE-031 2.5 mg/kg subcutaneously once every 4 weeks for 12 weeks. |
| FG003 | Placebo | Placebo: Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ACE-031 0.5 mg/kg q4wk | ACE-031 0.5 mg/kg q4wk: ACE-031 0.5 mg/kg subcutaneously once every 4 weeks for 12 weeks. |
| BG001 | ACE-031 1.0 mg/kg q2wk | ACE-031 1.0 mg/kg q2wk: ACE-031 1.0 mg/kg subcutaneously once every 2 weeks for 12 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Number | Number of subjects | From treatment initiation to End-of-Study Visit, approximately 24 weeks later |
|
24 weeks (12 weeks treatment period + 12 weeks follow up)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ACE-031 0.5 mg/kg q4wk | ACE-031 0.5 mg/kg q4wk: ACE-031 0.5 mg/kg subcutaneously once every 4 weeks for 12 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site erythema | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| ACE-031 1.0 mg/kg q2wk | Biological | ACE-031 1.0 mg/kg subcutaneously once every 2 weeks for 12 weeks. |
|
| Placebo | Other | Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks. |
|
| 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 |
| Vancouver |
| British Columbia |
| Canada |
| Acceleron Investigative Site | Hamilton | Ontario | Canada |
| Acceleron Investigative Site | London | Ontario | Canada |
| Acceleron Investigative Site | Ottawa | Ontario | Canada |
| BG002 | ACE-031 ACE-03 2.5 mg/kg q4wk | ACE-031 2.5 mg/kg q4wk: ACE-031 2.5 mg/kg subcutaneously once every 4 weeks for 12 weeks. |
| BG003 | Placebo | Placebo: Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Able to ambulate 10 meters in < 12 seconds | Number | participants |
|
| Placebo |
Placebo: Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks. |
|
|
| Primary | 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 | Posted | Number | Number of subjects | Baseline to End-of-Study Visit, approximately 24 weeks later. |
|
|
|
| Secondary | Percent Change in Total Lean Body Mass by DXA Scan. | Posted | Mean | Standard Error | percentage change in lean body mass | Baseline to End-of-Study Visit, approximately 24 weeks later. |
|
|
|
|
| Secondary | Percent Change in Lumbar Spine Bone Mineral Density by DXA Scan. | Posted | Mean | Standard Error | percentage change from baseline | Baseline to End-of-Study Visit, approximately 24 weeks later. |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | percentage change from baseline | Baseline to End-of-Study Visit, approximately 24 weeks later. |
|
|
|
| Secondary | 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) | Posted | Mean | Standard Deviation | change (m) in 6MWT from baseline | Baseline to End-of-Study Visit, approximately 24 weeks later. |
|
|
|
| Secondary | Change From Baseline in Time to Travel 10 Meters (Standardized 10-Meter-Walk/Run Test). | Posted | Mean | Standard Deviation | Change (sec) in 10MWT from baseline | Baseline to End-of-Study Visit, approximately 24 weeks later. |
|
|
|
| Secondary | Change in Pulmonary Function Tests (FVC) | Forced Vital Capacity (FVC); 1 of 3 separate tests employed to assess pulmonary function in this study | Posted | Mean | Standard Deviation | Liters | Baseline to End-of-Study Visit, approximately 24 weeks later. |
|
|
|
| Secondary | Change in Pulmonary Function Test (MIP) | Maximum Inspiratory Pressure (MIP); 2 of 3 separate tests employed to assess pulmonary function in this study | Posted | Mean | Standard Deviation | cm H2O | Baseline to End-of-Study Visit. approximately 24 weeks |
|
|
|
| Secondary | Change in Pulmonary Function Test (MEP) | Maximum Expiratory Pressure (MEP); 3 of 3 separate tests employed to assess pulmonary function in this study | Posted | Mean | Standard Deviation | cm H2O | Baseline to End-of-Stuidy Visit, approximately 24 weeks |
|
|
|
| 0 |
| 9 |
| 3 |
| 9 |
| EG001 | ACE-031 1.0 mg/kg q2wk | ACE-031 1.0 mg/kg q2wk: ACE-031 1.0 mg/kg subcutaneously once every 2 weeks for 12 weeks. | 0 | 9 | 6 | 9 |
| EG002 | ACE-031 ACE-03 2.5 mg/kg q4wk | ACE-031 2.5 mg/kg q4wk: ACE-031 2.5 mg/kg subcutaneously once every 4 weeks for 12 weeks. | 0 | 0 | 0 | 0 |
| EG003 | Placebo | Placebo: Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks. | 0 | 6 | 3 | 6 |
| epistaxis | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| telangiectasia | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| headache | General disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| 2-Sided |
| Superiority or Other (legacy) |
| ANCOVA | 0.435 | 2-Sided | Superiority or Other (legacy) |
|
| Knee extension (kg) |
|
| Knee flexion (kg) |
|
|