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.
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| ClinicalTrials.gov Identifier: NCT04179409 |
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Recruitment Status :
Completed
First Posted : November 27, 2019
Results First Posted : October 12, 2023
Last Update Posted : October 26, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Duchenne Muscular Dystrophy | Drug: Amondys 45 Drug: Exondys 51 Drug: Vyondys 53 | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 3 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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. |
| Actual Study Start Date : | February 18, 2020 |
| Actual Primary Completion Date : | September 1, 2021 |
| Actual Study Completion Date : | September 1, 2023 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Amondys 45
This drug is used to target skipping of exon 45 of the dystrophin gene.
Other Names:
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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.
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Drug: Exondys 51
This drug is used to target skipping of exon 51 of the dystrophin gene.
Other Names:
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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.
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Drug: Vyondys 53
This drug is used to target skipping of exon 53 of the dystrophin gene.
Other Names:
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- 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.
- 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.
- 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.
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| Ages Eligible for Study: | 6 Months and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
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): NCT04179409
| United States, Ohio | |
| Nationwide Children's Hospital | |
| Columbus, Ohio, United States, 43205 | |
| Principal Investigator: | Kevin Flanigan, MD | Nationwide Children's Hospital |
Documents provided by Kevin Flanigan, Nationwide Children's Hospital:
| Responsible Party: | Kevin Flanigan, Professor of Neurology, Nationwide Children's Hospital |
| ClinicalTrials.gov Identifier: | NCT04179409 |
| Other Study ID Numbers: |
SRPT-Dup-US-001 |
| First Posted: | November 27, 2019 Key Record Dates |
| Results First Posted: | October 12, 2023 |
| Last Update Posted: | October 26, 2023 |
| Last Verified: | October 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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DMD Exon Skipping |
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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 |