Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy

• ClinicalTrials.gov Identifier: NCT01099761
• Recruitment Status: Terminated
• First Posted: April 8, 2010
• Results First Posted: October 14, 2016
• Last Update Posted: October 13, 2022
• Sponsor: Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
• Information provided by (Responsible Party): Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Study Description

Brief Summary:

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]

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Biological: ACE-031 0.5 mg/kg q4wk; Biological: ACE-031 1.0 mg/kg q2wk; Other: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2010
• Actual Primary Completion Date: June 2011
• Actual Study Completion Date: June 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: ACE-031 0.5 mg/kg q4wk	Biological: ACE-031 0.5 mg/kg q4wk; ACE-031 0.5 mg/kg subcutaneously once every 4 weeks for 12 weeks.
Experimental: ACE-031 1.0 mg/kg q2wk	Biological: ACE-031 1.0 mg/kg q2wk; ACE-031 1.0 mg/kg subcutaneously once every 2 weeks for 12 weeks.
Placebo Comparator: Placebo	Other: Placebo; Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks.

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Adverse Reactions. [ Time Frame: 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
2. Number of Subjects With Clinical Laboratory Adverse Reactions. [ Time Frame: 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

Secondary Outcome Measures :

1. Percent Change in Total Lean Body Mass by DXA Scan. [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
2. Percent Change in Lumbar Spine Bone Mineral Density by DXA Scan. [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
3. Percent Change in Muscle Strength Score by Hand-held Myometry. [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
   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.
4. Change in Distance Traveled in 6 Minutes (Standardized 6-Minute-Walk Test). [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
   Change in distance traveled in 6 minutes (standardized 6-Minute-Walk Test); stratified by baseline age (<10 years vs. >=10 years)
5. Change From Baseline in Time to Travel 10 Meters (Standardized 10-Meter-Walk/Run Test). [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
6. Change in Pulmonary Function Tests (FVC) [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
   Forced Vital Capacity (FVC); 1 of 3 separate tests employed to assess pulmonary function in this study
7. Change in Pulmonary Function Test (MIP) [ Time Frame: Baseline to End-of-Study Visit. approximately 24 weeks ]
   Maximum Inspiratory Pressure (MIP); 2 of 3 separate tests employed to assess pulmonary function in this study
8. Change in Pulmonary Function Test (MEP) [ Time Frame: Baseline to End-of-Stuidy Visit, approximately 24 weeks ]
   Maximum Expiratory Pressure (MEP); 3 of 3 separate tests employed to assess pulmonary function in this study

Eligibility Criteria

• Ages Eligible for Study: 4 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

Acceleron Investigative Site

Calgary, Alberta, Canada

Canada, British Columbia

Acceleron Investigative Site

Vancouver, British Columbia, Canada

Canada, Ontario

Acceleron Investigative Site

Hamilton, Ontario, Canada

Acceleron Investigative Site

London, Ontario, Canada

Acceleron Investigative Site

Ottawa, Ontario, Canada

Sponsors and Collaborators

Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

More Information

• Responsible Party: Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
• ClinicalTrials.gov Identifier: NCT01099761
• Other Study ID Numbers: A031-03
• First Posted: April 8, 2010
• Results First Posted: October 14, 2016
• Last Update Posted: October 13, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: 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.

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked