Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01099761
• Other study ID #: A031-03
• Status: Terminated
• Phase: Phase 2
• Start date: April 2010
• Est. completion date: June 2011

Study information

• Verified date: September 2022
• Source: Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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]

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Biological:
• ACE-031 0.5 mg/kg q4wk
ACE-031 0.5 mg/kg subcutaneously once every 4 weeks for 12 weeks.
• ACE-031 1.0 mg/kg q2wk
ACE-031 1.0 mg/kg subcutaneously once every 2 weeks for 12 weeks.

Other:
• Placebo
Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks.

Locations

Country	Name	City	State
Canada	Acceleron Investigative Site	Calgary	Alberta
Canada	Acceleron Investigative Site	Hamilton	Ontario
Canada	Acceleron Investigative Site	London	Ontario
Canada	Acceleron Investigative Site	Ottawa	Ontario
Canada	Acceleron Investigative Site	Vancouver	British Columbia

Sponsors (1)

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

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	From treatment initiation to End-of-Study Visit, approximately 24 weeks later
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	Baseline to End-of-Study Visit, approximately 24 weeks later.
Secondary	Percent Change in Total Lean Body Mass by DXA Scan.		Baseline to End-of-Study Visit, approximately 24 weeks later.
Secondary	Percent Change in Lumbar Spine Bone Mineral Density by DXA Scan.		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.	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)	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).		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	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	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	Baseline to End-of-Stuidy Visit, approximately 24 weeks