Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy

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

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]

Study Overview

• Status: Terminated
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Biological: ACE-031 0.5 mg/kg q4wk; Biological: ACE-031 1.0 mg/kg q2wk; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Acceleron Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Acceleron Investigative Site
  • Ontario
    • Hamilton, Ontario, Canada
      • Acceleron Investigative Site
    • London, Ontario, Canada
      • Acceleron Investigative Site
    • Ottawa, Ontario, Canada
      • Acceleron Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks.
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.

What is the study measuring?

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: April 2, 2010
• First Submitted That Met QC Criteria: April 6, 2010
• First Posted (Estimate): April 8, 2010

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: September 14, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: A031-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD 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.