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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.

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.

Condition or disease Intervention/treatment Phase
Muscular Dystrophy, Duchenne Drug: Eteplirsen Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
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
Official Title: 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
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024


Arm Intervention/treatment
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.
Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS

Active Comparator: Part 2: Eteplirsen 30 mg/kg
Patients will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks.
Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS

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.
Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS

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.
Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS




Primary Outcome Measures :
  1. Part 1 and Part 2 (Dose Finding): Incidences of Adverse Events (AEs) [ Time Frame: Baseline up to Week 148 ]
  2. Part 2 (Dose Finding): Dystrophin Expression in Biopsied Muscle Tissue [ Time Frame: Up to Week 48 ]
  3. Part 2 (Dose Finding): Pharmacokinetic (PK) Plasma Concentration of Eteplirsen [ Time Frame: Multiple timepoints up to Week 48 ]
  4. Part 2 (Dose Finding): Tissue Concentration of Eteplirsen From Biopsied Muscle Tissue [ Time Frame: Up to Week 48 ]
  5. Part 2 (Dose Comparison): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score [ Time Frame: Baseline, Week 144 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Part 2 (Dose Comparison): Annual Rate in Decline of Forced Vital Capacity Percent Predicted (FVC%p) [ Time Frame: Up to Week 144 ]
  4. Part 2 (Dose Comparison): Time to Loss of Ambulation (LOA) [ Time Frame: Baseline up to Week 144 ]
  5. Part 2 (Dose Comparison): Change From Baseline in Skeletal Muscle Dystrophin Expression [ Time Frame: Baseline and Week 48 ]
  6. Part 2 (Dose Comparison): Incidence of Adverse Events (AEs) [ Time Frame: Baseline up to Week 144 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years to 13 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.


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): NCT03992430


Contacts
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Contact: Medical Information +1 888-727-3782 clinicaltrials@sarepta.com

Sponsors and Collaborators
Sarepta Therapeutics, Inc.
Investigators
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Study Director: Medical Director Sarepta Therapeutics, Inc.

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Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03992430     History of Changes
Other Study ID Numbers: 4658-402
First Posted: June 20, 2019    Key Record Dates
Last Update Posted: June 20, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sarepta Therapeutics, Inc.:
Duchenne muscular dystrophy
Exon Skipping
Exon 51
North Star Ambulatory Assessment
Ambulatory
DMD
Pediatric
Duchenne
EXONDYS
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