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Study of Eteplirsen in DMD Patients (PROMOVI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02255552
Recruitment Status : Completed
First Posted : October 2, 2014
Results First Posted : July 1, 2020
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE September 25, 2014
First Posted Date  ICMJE October 2, 2014
Results First Submitted Date  ICMJE June 12, 2020
Results First Posted Date  ICMJE July 1, 2020
Last Update Posted Date July 1, 2020
Actual Study Start Date  ICMJE November 17, 2014
Actual Primary Completion Date June 14, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 29, 2014)
Change in 6-Minute Walk Test (6MWT) distance from baseline [ Time Frame: Baseline, Weeks 12, 24, 36, 48 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2020)
  • 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. Data for this outcome measure was not planned to be collected and analyzed for Untreated Control group.
  • 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.
  • 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.
  • 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%.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2014)
  • The percentage of dystrophin-positive fibers [ Time Frame: Baseline, Weeks 24/48/TBD ]
  • Maximum inspiratory/expiratory pressure percent predicted (MIP/MEP % predicted) [ Time Frame: Baseline,Weeks 12, 24, 36, 48 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Eteplirsen in DMD Patients
Official Title  ICMJE An Open-Label, Multi-Center, Study With a Concurrent Untreated Control Arm to Evaluate the Efficacy and Safety of Eteplirsen in Duchenne Muscular Dystrophy
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy (DMD)
Intervention  ICMJE 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®
Study Arms  ICMJE
  • 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).
    Intervention: Drug: eteplirsen
  • No Intervention: Untreated Group
    Approximately 30 DMD patients not amenable to exon 51 skipping will not receive eteplirsen.
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 27, 2019)
109
Original Estimated Enrollment  ICMJE
 (submitted: September 29, 2014)
160
Actual Study Completion Date  ICMJE June 14, 2019
Actual Primary Completion Date June 14, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 7 Years to 16 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02255552
Other Study ID Numbers  ICMJE 4658-301
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sarepta Therapeutics, Inc.
Study Sponsor  ICMJE Sarepta Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Sarepta Therapeutics, Inc.
PRS Account Sarepta Therapeutics, Inc.
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP