A 48-Week, Open Label, Study to Evaluate the Efficacy and Safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 in Subjects With DuchenneMuscular Dystrophy Carrying Eligible DMD Duplications.

October 20, 2023 updated by: Kevin Flanigan
This is an 48-week open-label study to determine the efficacy and safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 for the treatment of boys with duchenne muscular dystrophy who have a single exon duplication of either exon 45, 51 or 53, respectively. There will be weekly infusions and two muscle biopsies at baseline and at month 12.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

DMD is a rare, serious, debilitating, and ultimately fatal, disease for which there is an urgent need to develop safe and effective therapies. In order to efficiently meet this urgency and the needs of the subject community, the study evaluates the efficacy and safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 administration over approximately 1 year in DMD subjects with duplication mutations amenable to treatment by exon 45, 51 or exon 53 skipping. Skipping of a single copy of the duplicated exon is expected to result in a wild-type (WT) DMD transcript allowing the expression of a WT, full length dystrophin protein. Successful skipping of a single copy of the duplicated exon in in vitro and in vivo models has been reported in the literature. AMONDYS 45, EXONDYS 51, VYONDYS 53 have the potential to be disease-modifying treatments for boys with DMD mutations amenable to exon 45, 51 and exon 53 skipping, respectively.

The totality of the non-clinical data with these PMOs as well as AVI-4225 (targeting exon 23) and EXONDYS 51 suggests that PMOs are well tolerated in the non-clinical setting. Moreover, treatment with EXONDYS 51(at 30 mg/kg and 50 mg/kg) has been well-tolerated by boys with DMD deletion mutations amenable to skipping exon 51. The relatively low expected risk for subjects exposed to AMONDYS 45, EXONDYS 51, VYONDYS 53 and the urgent medical need for a treatment for this subject population support the conclusion that the potential benefits of exposing subjects to AMONDYS 45, EXONDYS 51, VYONDYS 53 outweigh the potential risks.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Is a male with DMD and has an out-of-frame duplication of either exon 45, 51, or 53, with a normal copy number of all other DMD exons.
  • Is above age 6 months of age.
  • Has sufficient muscle mass in a pair of bilateral muscles that will allow for pre- and post-treatment muscle biopsies per PI discretion.
  • If the subject is ambulant and 4 years old or greater and has been on a stable dose or dose equivalent of oral corticosteroids for at least 12 weeks prior to Week 1 the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the study.

Exclusion Criteria:

  • Any additional missing exon for DMD that cannot be treated with study drugs.

Other inclusion/exclusion criteria apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AMONDYS 45
This arm will involve the treatment of boys with DMD who have a duplication of exon 45, for which AMONDYS 45 will target skipping of this exon.
Drug: Amondys 45
This drug is used to target skipping of exon 45 of the dystrophin gene.
Other Names:
  • SRP-4045
  • Casimersen
Experimental: EXONDYS 51
This arm will involve the treatment of boys with DMD who have a duplication of exon 51, for which EXONDYS 51 will target skipping of this exon.
Drug: Exondys 51
This drug is used to target skipping of exon 51 of the dystrophin gene.
Other Names:
  • AVI-4658
  • Eteplirsen
Experimental: VYONDYS 53
This arm will involve the treatment of boys with DMD who have a duplication of exon 53, for which VYONDYS 53 will target skipping of this exon.
Drug: Vyondys 53
This drug is used to target skipping of exon 53 of the dystrophin gene.
Other Names:
  • SRP-4053
  • Golodirsen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Monitoring for the Development of Unacceptable Toxicity.
Time Frame: 1 year
This will be measured by capturing and reviewing Adverse Events as defined by CTCAE v4.0.
1 year
Change in Dystrophin Expression From Baseline Following Treatment With Either AMONDYS 45 (Previously Casimersen), EXONDYS 51 (Previously Eteplirsen ), or VYONDYS 53 (Previously Golodirsen)
Time Frame: Baseline, 1 year
This will be assessed by the comparison of quantification of protein in muscle biopsy tissue by western blot from baseline to 1 year post-initiation of treatment.
Baseline, 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Dystrophin Expression From Baseline Following Treatment With Either AMONDYS 45 (Previously Casimersen), EXONDYS 51 (Previously Eteplirsen ), or VYONDYS 53 (Previously Golodirsen).
Time Frame: 1 year
This will be assessed by the comparison of immunofluorescent staining in muscle biopsy tissue from baseline to 1 year post-initiation of treatment.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kevin Flanigan

Collaborators

Sarepta Therapeutics, Inc.

Investigators

  • Principal Investigator: Kevin Flanigan, MD, Nationwide Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 18, 2020

Primary Completion (Actual)

September 1, 2021

Study Completion (Actual)

September 1, 2023

Study Registration Dates

First Submitted

August 12, 2019

First Submitted That Met QC Criteria

November 25, 2019

First Posted (Actual)

November 27, 2019

Study Record Updates

Last Update Posted (Actual)

October 26, 2023

Last Update Submitted That Met QC Criteria

October 20, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SRPT-Dup-US-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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