Confirmatory Study of Eteplirsen in DMD Patients (PROMOVI)

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The main objective of this study is to provide confirmatory evidence of efficacy of eteplirsen (AVI-4658) in Duchenne muscular dystrophy (DMD) patients that are amenable to skipping exon 51. Additional objectives include evaluation of safety, biomarkers and the long-term effects of eteplirsen up to 96 weeks, followed by a safety extension (not to exceed 48 weeks).

Sites are currently being initiated into the study. Initiation of approximately 39 planned sites in the United States is expected to be completed by June 2016. The initiated sites can be found in the "Contacts and Locations" section of this posting in addition to a listing of the city and states of sites the investigators are working to initiate. This information will be updated on a rolling basis as additional sites are initiated.

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy (DMD)	Drug: eteplirsen	Phase 3

Detailed Description:

This is an open-label, multi-center study to evaluate the efficacy and safety of eteplirsen in patients with genotypically confirmed Duchenne muscular dystrophy (DMD) with genetic deletions amenable to exon 51 skipping (treated group), with a concurrent control arm of DMD patients not amenable to exon 51 skipping (untreated group). Following primary efficacy endpoints, dosing will continue to week 144 to evaluate the long term effects of eteplirsen.

Patients in the treated group will receive once weekly intravenous (IV) infusions of 30 mg/kg Eteplirsen for 96 weeks, followed by a safety extension (not to exceed 48 weeks). Patients in the untreated group will not receive treatment.

Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests such as the six minute walk test. Patients in the treated group will undergo a muscle biopsy at Baseline and a second muscle biopsy over the course of the study. Patients in the untreated group will not undergo muscle biopsy.

Safety, including adverse event monitoring and routine laboratory assessments, will be continuously monitored for all patients.

The sponsor is working to initiate approximately 39 sites across the United States. Sites will vary in the following functions:

1. Local Site (N=39) - Enrolls patients and is the primary contact point for their patients. Sites will perform all protocol activities (including dosing and laboratory assessments), except for functional assessments and biopsies.
2. Hub Site (N=14) - Performs functional (physical) assessments at specified times per protocol.
3. Surgical Site (N=2) - Performs muscle biopsies for the Treated group.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	160 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open-Label, Multi-Center, Study With a Concurrent Untreated Control Arm to Evaluate the Efficacy and Safety of Eteplirsen in Duchenne Muscular Dystrophy
Study Start Date :	September 2014
Estimated Primary Completion Date :	January 2019
Estimated Study Completion Date :	May 2019

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Treated Group; Approximately 80 patients with genotypically confirmed Duchenne muscular dystrophy (DMD) with genetic deletions amenable to treatment by exon 51 skipping will receive 30 mg/kg of eteplirsen weekly for 96 weeks, followed by a safety extension (not to exceed 48 weeks).	Drug: eteplirsen; Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks, followed by a safety extension (not to exceed 48 weeks).; Other Names: AVI-4658; EXONDYS 51®
No Intervention: Untreated Group; Approximately 80 DMD patients not amenable to exon 51 skipping will not receive eteplirsen.

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Change in 6-Minute Walk Test (6MWT) distance from baseline [ Time Frame: Baseline, Weeks 12, 24, 36, 48 ]

Secondary Outcome Measures :

1. The percentage of dystrophin-positive fibers [ Time Frame: Baseline, Weeks 24, 48, 72, 96 ]
2. Maximum inspiratory/expiratory pressure percent predicted (MIP/MEP % predicted) [ Time Frame: Baseline,Weeks 12, 24, 36, 48 ]

Other Outcome Measures:

1. Evaluate the long-term effects of eteplirsen up to 96 weeks [ Time Frame: Week 1-96 ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	7 Years to 16 Years (Child)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Male 7-16 years old
• Diagnosed with DMD, genotypically confirmed
• Stable dose of corticosteroids for at least 24 weeks
• Have intact right and left alternative upper muscle groups
• Mean 6MWT greater than 300m (primary analysis on 300 to 450 meters)
• Stable pulmonary and cardiac function: predicted FVC equal to or greater than 50% and LVEF of greater than 50%

Exclusion Criteria:

• Previous treatment with drisapersen or any other RNA antisense agent or any gene therapy within the last 6 months
• Participation in any other DMD interventional clinical study within 12 weeks
• Major surgery within 3 months
• Presence of other clinically significant illness
• Major change in the physical therapy regime within 3 months

Other inclusion/exclusion criteria apply.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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Locations

United States, Arizona
Neuromuscular Research Center
Phoenix, Arizona, United States, 85028
United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
University of California, Davis Medical Center
Sacramento, California, United States, 95817
Rady Children's Hospital, U.C. San Diego
San Diego, California, United States, 92130
Stanford University School of Medicine/Medical Center
Stanford, California, United States, 94305
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, District of Columbia
Children's National Health System
Washington, D.C., District of Columbia, United States, 20010
United States, Florida
The University of Florida, Powell Gene Therapy Center
Gainesville, Florida, United States, 32610
NW FL Clinical Research Group, LLC
Gulf Breeze, Florida, United States, 32561
Nemours Children's Hospital
Orlando, Florida, United States, 32827
United States, Georgia
Rare Disease Research Center
Atlanta, Georgia, United States, 30318
Emory University
Atlanta, Georgia, United States, 30324
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
University of Rochester Clinical Research Center
Rochester, New York, United States, 14642
United States, North Carolina
Levine Childrens Hospital, Carolinas Medical Center
Charlotte, North Carolina, United States, 28207
United States, Ohio
Cincinnati Children's Hospital Medical Center (CCHMC)
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Shriners Hospital for Children
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
The University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105

Sponsors and Collaborators

Sarepta Therapeutics

Investigators

Study Chair:	Chris Mix, MD	Sarepta Therapeutics
Study Chair:	Catherine Stehman-Breen, MD, MS	Sarepta Therapeutics

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Sarepta Therapeutics
ClinicalTrials.gov Identifier:	NCT02255552 History of Changes
Other Study ID Numbers:	4658-301
First Posted:	October 2, 2014
Last Update Posted:	October 3, 2017
Last Verified:	October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Sarepta Therapeutics:

DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51

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