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Study of Eteplirsen in DMD Patients (PROMOVI)

Primary Purpose

Duchenne Muscular Dystrophy (DMD)

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
eteplirsen
Sponsored by
Sarepta Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Duchenne Muscular Dystrophy (DMD) focused on measuring DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51

Eligibility Criteria

7 Years - 16 Years (Child)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Neuromuscular Research Center
  • David Geffen School of Medicine at UCLA
  • University of California, Davis Medical Center
  • Rady Children's Hospital, U.C. San Diego
  • Stanford University School of Medicine/Medical Center
  • Children's Hospital Colorado
  • Connecticut Children's Medical Center
  • Children's National Health System
  • The University of Florida, Powell Gene Therapy Center
  • NW FL Clinical Research Group, LLC
  • Nemours Children's Hospital
  • Rare Disease Research Center
  • Emory University
  • Ann and Robert H. Lurie Children's Hospital of Chicago
  • University of Iowa Children's Hospital
  • University of Kansas Medical Center
  • Kennedy Krieger Institute
  • Massachusetts General Hospital
  • Children's Hospital Boston
  • Children's Hospital of Michigan
  • University of Minnesota
  • St. Louis Children's Hospital
  • Dartmouth-Hitchcock Medical Center
  • Columbia University Medical Center
  • University of Rochester Clinical Research Center
  • Levine Childrens Hospital, Carolinas Medical Center
  • Cincinnati Children's Hospital Medical Center (CCHMC)
  • Nationwide Children's Hospital
  • Shriners Hospital for Children
  • Penn State Hershey Medical Center
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC
  • Vanderbilt University Medical Center
  • The University of Texas Southwestern Medical Center
  • Texas Children's Hospital
  • University of Utah
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treated Group

Untreated Group

Arm Description

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).

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

Outcomes

Primary Outcome Measures

Change From Baseline in the 6 Minute Walk Test (6MWT) Distance at 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

Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at 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.
Number of Participants Having Ability to Rise Independently From the Floor Determined Based on North Star Ambulatory Assessment (NSAA) at 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.
Number of Participants Who Lost Ambulation (LOA) by 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.
Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Weeks 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%.
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Scores at 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.
Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 96
Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry.

Full Information

First Posted
September 25, 2014
Last Updated
December 31, 2020
Sponsor
Sarepta Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02255552
Brief Title
Study of Eteplirsen in DMD Patients
Acronym
PROMOVI
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 Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
November 17, 2014 (Actual)
Primary Completion Date
June 14, 2019 (Actual)
Study Completion Date
June 14, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarepta Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy (DMD)
Keywords
DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
109 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treated Group
Arm Type
Experimental
Arm Description
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).
Arm Title
Untreated Group
Arm Type
No Intervention
Arm Description
Approximately 30 DMD patients not amenable to exon 51 skipping will not receive eteplirsen.
Intervention Type
Drug
Intervention Name(s)
eteplirsen
Other Intervention Name(s)
AVI-4658, EXONDYS 51®
Intervention Description
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).
Primary Outcome Measure Information:
Title
Change From Baseline in the 6 Minute Walk Test (6MWT) Distance at Week 96
Description
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.
Time Frame
Baseline, Week 96
Secondary Outcome Measure Information:
Title
Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 96
Description
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.
Time Frame
Baseline, Week 96
Title
Number of Participants Having Ability to Rise Independently From the Floor Determined Based on North Star Ambulatory Assessment (NSAA) at Week 96
Description
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.
Time Frame
Week 96
Title
Number of Participants Who Lost Ambulation (LOA) by Week 96
Description
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.
Time Frame
Up to Week 96
Title
Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Weeks 96
Description
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%.
Time Frame
Baseline, Week 96
Title
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Scores at Week 96
Description
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.
Time Frame
Baseline, Week 96
Title
Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 96
Description
Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry.
Time Frame
Baseline, Week 96

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sarepta Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Neuromuscular Research Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85028
Country
United States
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Rady Children's Hospital, U.C. San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92130
Country
United States
Facility Name
Stanford University School of Medicine/Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Connecticut Children's Medical Center
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Children's National Health System
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
The University of Florida, Powell Gene Therapy Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
NW FL Clinical Research Group, LLC
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Rare Disease Research Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30324
Country
United States
Facility Name
Ann and Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester Clinical Research Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Levine Childrens Hospital, Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center (CCHMC)
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Shriners Hospital for Children
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Penn State Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
The University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31237898
Citation
Brogna C, Coratti G, Pane M, Ricotti V, Messina S, D'Amico A, Bruno C, Vita G, Berardinelli A, Mazzone E, Magri F, Ricci F, Mongini T, Battini R, Bello L, Pegoraro E, Baranello G, Previtali SC, Politano L, Comi GP, Sansone VA, Donati A, Bertini E, Muntoni F, Goemans N, Mercuri E; on behalf on the International DMD group. Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53. PLoS One. 2019 Jun 25;14(6):e0218683. doi: 10.1371/journal.pone.0218683. eCollection 2019. Erratum In: PLoS One. 2019 Jul 31;14(7):e0220714.
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Study of Eteplirsen in DMD Patients

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