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Duchenne Muscular DystrophyPhase 2NCT04179409

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.

A Phase 2 study testing Amondys 45, Exondys 51 and Vyondys 53 in people with Duchenne Muscular Dystrophy, run by Kevin Flanigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 6 months and older, men only
Conditions the study is for
Duchenne Muscular Dystrophy
What is being tested?
Amondys 45, Exondys 51 and Vyondys 53
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
18 Feb 2020to 1 Sep 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months and older
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • Any additional missing exon for DMD that cannot be treated with study drugs.
  • Other inclusion/exclusion criteria apply

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

Other trials in United States

About this study

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.

Read the 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.

Being tested
Amondys 45, Exondys 51, Vyondys 53
Keywords
DMD, Exon Skipping
Medical subject headings
Muscular Dystrophy, Duchenne

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Amondys 45Drug

    Also called SRP-4045, Casimersen

    This drug is used to target skipping of exon 45 of the dystrophin gene.

  • Exondys 51Drug

    Also called Eteplirsen, AVI-4658

    This drug is used to target skipping of exon 51 of the dystrophin gene.

  • Vyondys 53Drug

    Also called SRP-4053, Golodirsen

    This drug is used to target skipping of exon 53 of the dystrophin gene.

Study groups in NCT04179409
Study groupRoleWhat they receive
AMONDYS 45ExperimentalThis 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.
Receives: Drug: Amondys 45
EXONDYS 51ExperimentalThis 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.
Receives: Drug: Exondys 51
VYONDYS 53ExperimentalThis 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.
Receives: Drug: Vyondys 53

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Dystrophin Expression From Baseline Following Treatment With Either AMONDYS 45 (Previously Casimersen), EXONDYS 51 (Previously Eteplirsen ), or VYONDYS 53 (Previously Golodirsen)

    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.

    Measured: Baseline, 1 year

  2. Monitoring for the Development of Unacceptable Toxicity.

    This will be measured by capturing and reviewing Adverse Events as defined by CTCAE v4.0.

    Measured: 1 year

Secondary outcomes (1)

  1. Change in Dystrophin Expression From Baseline Following Treatment With Either AMONDYS 45 (Previously Casimersen), EXONDYS 51 (Previously Eteplirsen ), or VYONDYS 53 (Previously Golodirsen).

    This will be assessed by the comparison of immunofluorescent staining in muscle biopsy tissue from baseline to 1 year post-initiation of treatment.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2019
  2. Study start18 Feb 2020
  3. Primary completion1 Sep 2021
  4. Study completion1 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04179409
Sponsor's protocol ID
SRPT-Dup-US-001
Status last verified
Oct 2023
First submitted
12 Aug 2019
Last updated
26 Oct 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar I, van Deutekom J, van Ommen GJ, den Dunnen JT. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat. 2009 Mar;30(3):293-9. doi: 10.1002/humu.20918.

    PubMed 19156838

  • Greer KL, Lochmuller H, Flanigan K, Fletcher S, Wilton SD. Targeted exon skipping to correct exon duplications in the dystrophin gene. Mol Ther Nucleic Acids. 2014 Mar 18;3(3):e155. doi: 10.1038/mtna.2014.8.

    PubMed 24643206

  • Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L, Gomez AM, Lewis S, Kota J, Malik V, Shontz K, Walker CM, Flanigan KM, Corridore M, Kean JR, Allen HD, Shilling C, Melia KR, Sazani P, Saoud JB, Kaye EM; Eteplirsen Study Group. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013 Nov;74(5):637-47. doi: 10.1002/ana.23982. Epub 2013 Sep 10.

    PubMed 23907995

  • Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, Kaye EM, Mercuri E; Eteplirsen Study Group and Telethon Foundation DMD Italian Network. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016 Feb;79(2):257-71. doi: 10.1002/ana.24555. Epub 2016 Jan 8.

    PubMed 26573217

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Amondys 45, Exondys 51 and Vyondys 53 in people with Duchenne Muscular Dystrophy, run by Kevin Flanigan at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04179409, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2023.

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