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A Study to Compare Safety and Efficacy of a High Dose of Eteplirsen in Duchenne Muscular Dystrophy (DMD) Patients

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ClinicalTrials.gov Identifier: NCT03992430
Recruitment Status : Not yet recruiting
First Posted : June 20, 2019
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE June 18, 2019
First Posted Date  ICMJE June 20, 2019
Last Update Posted Date June 20, 2019
Estimated Study Start Date  ICMJE August 2019
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2019)
  • Part 1 and Part 2 (Dose Finding): Incidences of Adverse Events (AEs) [ Time Frame: Baseline up to Week 148 ]
  • Part 2 (Dose Finding): Dystrophin Expression in Biopsied Muscle Tissue [ Time Frame: Up to Week 48 ]
  • Part 2 (Dose Finding): Pharmacokinetic (PK) Plasma Concentration of Eteplirsen [ Time Frame: Multiple timepoints up to Week 48 ]
  • Part 2 (Dose Finding): Tissue Concentration of Eteplirsen From Biopsied Muscle Tissue [ Time Frame: Up to Week 48 ]
  • Part 2 (Dose Comparison): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score [ Time Frame: Baseline, Week 144 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2019)
  • Part 2 (Dose Comparison): Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) [ Time Frame: Baseline up to Week 144 ]
  • Part 2 (Dose Comparison): Change From Baseline in Time to Complete Walk/run, Stairs and Time to Rise [ Time Frame: Baseline up to Week 144 ]
  • Part 2 (Dose Comparison): Annual Rate in Decline of Forced Vital Capacity Percent Predicted (FVC%p) [ Time Frame: Up to Week 144 ]
  • Part 2 (Dose Comparison): Time to Loss of Ambulation (LOA) [ Time Frame: Baseline up to Week 144 ]
  • Part 2 (Dose Comparison): Change From Baseline in Skeletal Muscle Dystrophin Expression [ Time Frame: Baseline and Week 48 ]
  • Part 2 (Dose Comparison): Incidence of Adverse Events (AEs) [ Time Frame: Baseline up to Week 144 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Compare Safety and Efficacy of a High Dose of Eteplirsen in Duchenne Muscular Dystrophy (DMD) Patients
Official Title  ICMJE A Randomized, Double-Blind, Dose Finding and Comparison Study of the Safety and Efficacy of a High Dose of Eteplirsen, Preceded by an Open-label Dose Escalation, in Patients With Duchenne Muscular Dystrophy With Deletion Mutations Amenable to Exon 51 Skipping
Brief Summary This study will be comprised of 2 parts: Part 1 will be conducted to evaluate the safety and tolerability of two doses (high dose level 1 and high dose level 2) of eteplirsen in approximately 8 patients; Part 2 will be conducted for the selection of a high dose (high dose level 1 vs high dose level 2) (dose finding phase), and its comparison with the 30 mg/kg dose of eteplirsen (dose comparison phase), in approximately 144 DMD patients with genetically confirmed deletion mutations amenable to treatment by skipping exon 51.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Part 1 is open-label, dose escalation; Part 2 is double-blind, dose finding and dose comparison
Primary Purpose: Treatment
Condition  ICMJE Muscular Dystrophy, Duchenne
Intervention  ICMJE Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS
Study Arms  ICMJE
  • Experimental: Part 1: Eteplirsen
    Patients will receive high dose level 1 of eteplirsen once weekly for at least 4 weeks, followed by high dose level 2 of eteplirsen once weekly for at least 4 weeks. Patients will continue treatment with the selected high dose as a distinct cohort for up to 144 weeks.
    Intervention: Drug: Eteplirsen
  • Active Comparator: Part 2: Eteplirsen 30 mg/kg
    Patients will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks.
    Intervention: Drug: Eteplirsen
  • Experimental: Part 2: Eteplirsen-High Dose Level 1
    Patients will receive high dose level 1 of eteplirsen once weekly before the selection of high dose occurs and then the selected high dose once weekly for up to 144 weeks.
    Intervention: Drug: Eteplirsen
  • Experimental: Part 2: Eteplirsen-High Dose Level 2
    Patients will receive high dose level 2 of eteplirsen once weekly before the selection of high dose occurs and then the selected high dose once weekly for up to 144 weeks.
    Intervention: Drug: Eteplirsen
Publications * Not Provided

*   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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 18, 2019)
152
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2024
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Be a male with an established clinical diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping.
  • Have achieved a mean 6-minute walk test (6MWT) distance of greater than equal to (>=) 300 and less than equal to (<=) 450 meters.
  • Have intact right and left biceps muscles or an alternative upper arm muscle group.
  • Have been on a stable dose or dose equivalent of oral corticosteroids for at least 24 weeks prior to randomization.
  • Have stable pulmonary function (forced vital capacity >= 50 percent (%) of predicted and no requirement for nocturnal ventilation).

Exclusion Criteria:

  • Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to randomization.
  • Current or previous treatment with gene therapy or any other experimental pharmacologic treatment for DMD; some exceptions apply.
  • Previous treatment with drisapersen, ezutromid, or domagrozumab in the last 24 weeks prior to study enrollment.
  • Major surgery within 3 months prior to randomization.
  • Presence of any other significant neuromuscular or genetic disease other than DMD.
  • Presence of other clinically significant illness.
  • Has evidence of cardiomyopathy, as defined by left ventricular ejection fraction less than (<) 50% on the screening Echocardiogram or QTcF >= 450 millisecond based on the screening ECGs.

Other inclusion/exclusion criteria apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 7 Years to 13 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Information +1 888-727-3782 clinicaltrials@sarepta.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03992430
Other Study ID Numbers  ICMJE 4658-402
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
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 2019

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