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.

NCT04179409 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: SRPT-Dup-US-001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. There will be weekly infusions and two muscle biopsies at baseline and at month 12.

Conditions

Duchenne Muscular Dystrophy

Keywords

DMD; Exon Skipping

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, 1 year

• Monitoring for the Development of Unacceptable Toxicity.

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

  1 year

Secondary Outcomes (1)

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

  1 year

Study Arms (3)

AMONDYS 45

EXPERIMENTAL

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

EXONDYS 51

EXPERIMENTAL

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

VYONDYS 53

EXPERIMENTAL

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

Interventions

Amondys 45 DRUG

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

Also known as: SRP-4045, Casimersen

AMONDYS 45

Exondys 51 DRUG

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

Also known as: Eteplirsen, AVI-4658

EXONDYS 51

Vyondys 53 DRUG

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

Also known as: SRP-4053, Golodirsen

VYONDYS 53

Eligibility Criteria

• Age: 6 Months+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Kevin Flanigan: lead
• Sarepta Therapeutics, Inc.: collaborator

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (4)

• 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.

  PMID: 19156838 BACKGROUND

• 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.

  PMID: 24643206 BACKGROUND

• 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.

  PMID: 23907995 BACKGROUND

• 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.

  PMID: 26573217 BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

casimersen; eteplirsen; golodirsen

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dr. Kevin Flanigan, Center for Gene Therapy Director
• Organization: Abigail Wexner Research Institute, Nationwide Children's Hospital

kevin.flanigan@nationwidechildrens.org

614-722-5615

Study Officials

• Kevin Flanigan, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: August 12, 2019
• First Posted: November 27, 2019
• Study Start: February 18, 2020
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2023
• Last Updated: October 26, 2023
• Results First Posted: October 12, 2023

Record last verified: 2023-10

Locations

US (1)