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A Study to Compare Safety and Efficacy of a High Dose of Eteplirsen in Participants With Duchenne Muscular Dystrophy (DMD) (MIS51ON)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03992430
Recruitment Status : Recruiting
First Posted : June 20, 2019
Last Update Posted : May 26, 2023
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Study Description
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Brief Summary:
This study will be comprised of 2 parts: Part 1 (dose escalation) will be conducted to evaluate the safety and tolerability of 2 doses (100 milligrams/kilogram [mg/kg] and 200 mg/kg) of eteplirsen in approximately 10 participants with DMD; Part 2 (dose finding and dose comparison) will be conducted for the selection of a high dose (100 mg/kg versus 200 mg/kg) and its comparison with the 30 mg/kg dose of eteplirsen, in approximately 144 participants 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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 154 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
Actual Study Start Date : July 13, 2020
Estimated Primary Completion Date : November 30, 2024
Estimated Study Completion Date : November 30, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Eteplirsen

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: Eteplirsen
Participants will receive eteplirsen 100 mg/kg once weekly for at least 4 weeks, followed by eteplirsen 200 mg/kg once weekly for at least 4 weeks.
 Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS
Active Comparator: Part 2: Eteplirsen 30 mg/kg
Randomized participants 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 100 mg/kg
Randomized participants will receive eteplirsen 100 mg/kg once weekly before the selection of the high dose occurs and then will receive 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 200 mg/kg
Randomized participants will receive eteplirsen 200 mg/kg once weekly before the selection of the high dose occurs and then will receive 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


Outcome Measures
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Primary Outcome Measures :
  1. Part 1: Incidence of Adverse Events (AEs) [ Time Frame: Up to Week 148 ]
  2. Part 2: Change From Baseline in the NSAA Total Score at Week 144 [ Time Frame: Baseline, Week 144 ]

Secondary Outcome Measures :
  1. Part 2: Change From Baseline in Time to Rise From the Floor, Time to Complete 10-Meter Walk/Run, and the Timed Stair Ascend Test [ Time Frame: Baseline, Week 144 ]
  2. Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) [ Time Frame: Baseline, Week 144 ]
  3. Part 2: Change from Baseline in Forced Vital Capacity Percent Predicted (FVC%p) at Week 144 [ Time Frame: Baseline, Week 144 ]
  4. Part 2: Time to Loss of Ambulation (LOA) [ Time Frame: Baseline up to Week 144 ]
  5. Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression [ Time Frame: Baseline, Postdose (at Week 24, Week 48, or Week 144) ]
  6. Part 2: Incidence of Adverse Events (AEs) [ Time Frame: Baseline up to Week 148 ]
  7. Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen [ Time Frame: 0 (predose) to 2 hours postdose up to Week 144 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   4 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.
  • Ambulatory participant, able to perform TTRISE in 10 seconds or less at the time of screening visit.
  • Able to walk independently without assistive devices.
  • 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 12 weeks prior to randomization and the dose is expected to remain constant (except for modifications to accommodate changes in weight and stress-related needs as per the recently published guidelines throughout the study.
  • For ages 7 years and older, has stable pulmonary function (forced vital capacity ≥50 percent (%) of predicted and no requirement for nocturnal ventilation). For ages 4 to 6 years, does not require support from ventilator or non-invasive ventilation at time of screening.

Exclusion Criteria:

  • Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to randomization.
  • Current or previous treatment with any other experimental pharmacologic treatment for DMD or any prior exposure to antisense oligonucleotide, gene therapy or gene editing; except the following: Ezutromid in the last 12 weeks prior to first dose; Drisapersen in the last 36 weeks prior to first dose; Suvodirsen in the last 12 weeks prior to first dose; Vamorolone in the last 12 weeks prior to first dose; and Eteplirsen (previous or current use).
  • Major surgery within 3 months prior to randomization.
  • Presence of any other significant neuromuscular or genetic disease other than DMD.
  • Presence of any known impairment of renal function and/or other clinically significant illness.
  • Has evidence of cardiomyopathy, as defined by left ventricular ejection fraction less than <50% on the screening echocardiogram or Fridericia's correction formula (QTcF) ≥450 millisecond based on the screening electrocardiograms (ECGs).

Other inclusion/exclusion criteria apply.

Contacts and Locations
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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: Sarepta Therapeutics Inc. For Clinical Trial Information, Select Option 4 1-888-SAREPTA (1-888-727-3782) SareptAlly@sarepta.com

Locations
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Sponsors and Collaborators
Sarepta Therapeutics, Inc.
Investigators
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Study Director: Medical Director Sarepta Therapeutics, Inc.
More Information
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Additional Information:

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Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03992430    
Other Study ID Numbers: 4658-402
First Posted: June 20, 2019    Key Record Dates
Last Update Posted: May 26, 2023
Last Verified: May 2023

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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
MIS51ON
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