A 48-Week, Open Label, Study to Evaluate the Efficacy and Safety of Casimersen, Eteplirsen and Golodirsen in Subjects With Duchenne Muscular Dystrophy Carrying Eligible DMD Duplications
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| ClinicalTrials.gov Identifier: NCT04179409 |
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Recruitment Status :
Active, not recruiting
First Posted : November 27, 2019
Last Update Posted : October 12, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Duchenne Muscular Dystrophy | Drug: Casimersen Drug: Eteplirsen Drug: Golodirsen | 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 casimersen, eteplirsen, and of golodirsen 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. Casimersen, eteplirsen, and golodirsen 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 eteplirsen suggests that PMOs are well tolerated in the non-clinical setting. Moreover, treatment with eteplirsen (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 casimersen, eteplirsen, or golodirsen and the urgent medical need for a treatment for this subject population support the conclusion that the potential benefits of exposing subjects to casimersen, eteplirsen, or golodirsen 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 Casimersen, Eteplirsen and Golodirsen in Subjects With Duchenne Muscular Dystrophy Carrying Eligible DMD Duplications |
| Actual Study Start Date : | February 18, 2020 |
| Actual Primary Completion Date : | September 1, 2021 |
| Estimated Study Completion Date : | September 1, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Casimersen
This arm will involve the treatment of boys with DMD who have a duplication of exon 45, for which casimersen will target skipping of this exon.
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Drug: Casimersen
This drug is used to target skipping of exon 45 of the dystrophin gene.
Other Name: SRP-4045 |
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Experimental: Eteplirsen
This arm will involve the treatment of boys with DMD who have a duplication of exon 51, for which eteplirsen will target skipping of this exon.
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Drug: Eteplirsen
This drug is used to target skipping of exon 51 of the dystrophin gene.
Other Names:
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Experimental: Golodirsen
This arm will involve the treatment of boys with DMD who have a duplication of exon 53, for which golodirsen will target skipping of this exon.
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Drug: Golodirsen
This drug is used to target skipping of exon 53 of the dystrophin gene.
Other Name: SRP-4053 |
- Change in dystrophin expression from baseline following treatment with either casimersen (previously SRP-4045), eteplirsen (previously AVI-4658), or golodirsen (previously SRP-4053). [ Time Frame: 1 year ]This will be assessed by quantification of protein in muscle biopsy tissue by western blot.
- Monitoring for the development of unacceptable toxicity. [ Time Frame: 1 year ]This will be measured by capturing and reviewing Adverse Events ad defined by CTCAE v4.0.
- Change in dystrophin expression from baseline following treatment with either casimersen (previously SRP-4045), eteplirsen (previously AVI-4658), or golodirsen (previously SRP-4053). [ Time Frame: 1 year ]Expression of dystrophin will be measured by immunofluorescent staining in muscle tissue sections in comparison to baseline values
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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 |
| 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 |
| Last Update Posted: | October 12, 2021 |
| Last Verified: | October 2021 |
| 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 |