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Study of Eteplirsen in DMD Patients (PROMOVI)

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ClinicalTrials.gov Identifier: NCT02255552
Recruitment Status : Completed
First Posted : October 2, 2014
Results First Posted : July 1, 2020
Last Update Posted : January 25, 2021
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Brief Summary:
The main objective of this study is to provide 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).

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 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
Actual Study Start Date : November 17, 2014
Actual Primary Completion Date : June 14, 2019
Actual Study Completion Date : June 14, 2019


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 30 DMD patients not amenable to exon 51 skipping will not receive eteplirsen.



Primary Outcome Measures :
  1. Change From Baseline in the 6 Minute Walk Test (6MWT) Distance at Week 96 [ Time Frame: Baseline, Week 96 ]
    6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course of 25 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at Week 96 was reported.


Secondary Outcome Measures :
  1. Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 96 [ Time Frame: Baseline, Week 96 ]
    Change from baseline in dystrophin protein levels (in muscle biopsy samples) were determined by Western blot. For each time point, 2 blocks of tissues were analyzed by Western blot, each with 2 replicates of gels to determine the dystrophin level as compared to a healthy individual (Percent Normal). The block average value from 2 replicate gels was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for all analyses. In case only 1 gel was available for a block, then that value was used as the block average value.

  2. Number of Participants Having Ability to Rise Independently From the Floor Determined Based on North Star Ambulatory Assessment (NSAA) at Week 96 [ Time Frame: Week 96 ]
    NSAA is a clinician-administered scale that rates participant performance on 17-items and included assessments of abilities such as 10-meter walk/run, rising from a sit to stand, standing on 1 leg, climbing a box step, descending a box step, rising from lying to sitting, rising from the floor, lifting the head, standing on heels, and jumping. For all activities, participants were graded as follows: 0 = unable to achieve goal independently; 1 = modified method but achieves goal independent of physical assistance from another and 2 = normal, no obvious modification of activity. Number of participants having ability to rise independently from the floor indicated by a NSAA Rise from floor sub score greater than 0 (unable to achieve goal independently) was reported.

  3. Number of Participants Who Lost Ambulation (LOA) by Week 96 [ Time Frame: Up to Week 96 ]
    Number of participants who lost ambulation (LOA) by Week 96 was reported. Participant were considered non-ambulatory if each of the 3 conditions below were met: NSAA walk subscore was "0" (unable to achieve goal independently) on 2 consecutive days within a visit or NSAA was not done due to reason related to non-ambulation; 6MWT was not done with any reason related to permanent non-ambulation; and no later data showing this participant was still ambulatory. This was not required if non ambulatory status occurred at the time of early withdrawal or at the end of Week 96 assessment. NSAA is a 17-item scale to assess the participant's abilities; total score range from 0 (if all the activities are failed) to 34 (if all the activities are achieved) with higher scores indicating better performance on the assessment/ fully-independent function.

  4. Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Weeks 96 [ Time Frame: Baseline, Week 96 ]
    FVC is the total amount of air exhaled during the forced expiratory volume test that is measured during spirometry; and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which is used to dilate participant's bronchial (breathing) tubes. Percent of predicted FVC = (observed value) / (predicted value) * 100%.

  5. Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Scores at Week 96 [ Time Frame: Baseline, Week 96 ]
    NSAA is a clinician-administered scale that rates participant performance on 17-items and included assessments of abilities such as 10-meter walk/run, rising from a sit to stand, standing on 1 leg, climbing a box step, descending a box step, rising from lying to sitting, rising from the floor, lifting the head, standing on heels, and jumping. Participant were graded as follows: 0 = unable to achieve goal independently; 1 = modified method but achieves goal independent of physical assistance from another and 2 = normal, no obvious modification of activity. NSAA total score was derived by summing the scores for all the individual items and range from 0 (if all the activities are failed) to 34 (if all the activities are achieved) with higher scores indicating better performance on the assessment/ fully-independent function.

  6. Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 96 [ Time Frame: Baseline, Week 96 ]
    Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry.



Information from the National Library of Medicine

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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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02255552


Locations
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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, 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, Inc.
Investigators
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Study Director: Medical Director Sarepta Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by Sarepta Therapeutics, Inc.:
Study Protocol  [PDF] June 2, 2017
Statistical Analysis Plan  [PDF] August 5, 2019

Publications:
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Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02255552    
Other Study ID Numbers: 4658-301
First Posted: October 2, 2014    Key Record Dates
Results First Posted: July 1, 2020
Last Update Posted: January 25, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Sarepta Therapeutics, Inc.:
DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked