AAV9 U7snRNA Gene Therapy to Treat Boys With DMD Exon 2 Duplications.

NCT04240314 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: AAV9 Dup2 U7
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Open-label, single dose clinical trial of scAAV9.U7.ACCA via peripheral limb vein injection for Duchenne muscular dystrophy boys who have a duplication of exon 2.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Unacceptable Toxicity.

  Unacceptable toxicity is defined as the occurrence of two or more unexpected Grade III or higher treatment-related toxicities, as defined by CTCAE 5.0.

  2 years

Secondary Outcomes (3)

• Change in Dystrophin Expression From Baseline Following Treatment With scAAV9.U7.ACCA.

  1 year

• Change in Dystrophin Expression From Baseline Following Treatment With scAAV9.U7.ACCA.

  1 year

• Changes in Percent of Exon 2 Skipping/Exclusion in the Dystrophin mRNA Transcript.

  1 year

Study Arms (1)

Cohort 1 (Minimal Efficacious Dose)

EXPERIMENTAL

The Minimal Effective Dose (MED) will be delivered.

Biological: scAAV9.U7.ACCA

Interventions

scAAV9.U7.ACCA BIOLOGICAL

A single dose of scAAV9.U7.ACCA will be systemically delivered via a peripheral vein injection.

Cohort 1 (Minimal Efficacious Dose)

Eligibility Criteria

• Age: 6 Months - 13 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age greater than 6 months and less than 14 years
• Confirmed duplication of exon 2 in the DMD gene using a clinically accepted technique that completely defines the mutation
• Pre-ambulant (not yet walking) or ambulant (as defined by the ability to walk 10 meters without assistance)
• Males of any ethnic group will be eligible
• Ability to cooperate with muscle testing
• In subjects age 4 and above, stable dose and regimen of corticosteroid therapy (prednisone, deflazacort, or their generic forms) for at least 12 weeks prior to gene transfer.

You may not qualify if:

• Active viral infection based on clinical observations
• Symptoms or signs of cardiomyopathy, including:
• Dyspnea on exertion, pedal edema, shortness of breath upon lying flat, or rales at the base of the lungs
• Echocardiogram with ejection fraction below 40%
• Serological evidence of HIV infection, or Hepatitis B or C infection
• Diagnosis of (or ongoing treatment for) an autoimmune disease
• Persistent leukopenia or leukocytosis (WBC ≤ 3.5 K/µL or ≥ 20.0 K/µL) or an absolute neutrophil count \< 1.5K/µL
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the SI creates unnecessary risks for gene transfer
• AAV9 binding antibody titers ≥ 1:400 as determined by ELISA immunoassay
• Abnormal laboratory values in the clinically significant range as listed in Table 7, based upon normal values in the Nationwide Children's Hospital Laboratory.

Sponsors & Collaborators

• Megan Waldrop: lead
• Audentes Therapeutics: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (5)

• Wein N, Vulin A, Falzarano MS, Szigyarto CA, Maiti B, Findlay A, Heller KN, Uhlen M, Bakthavachalu B, Messina S, Vita G, Passarelli C, Brioschi S, Bovolenta M, Neri M, Gualandi F, Wilton SD, Rodino-Klapac LR, Yang L, Dunn DM, Schoenberg DR, Weiss RB, Howard MT, Ferlini A, Flanigan KM. Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. Nat Med. 2014 Sep;20(9):992-1000. doi: 10.1038/nm.3628. Epub 2014 Aug 10.

  PMID: 25108525 BACKGROUND

• Vulin A, Wein N, Simmons TR, Rutherford AM, Findlay AR, Yurkoski JA, Kaminoh Y, Flanigan KM. The first exon duplication mouse model of Duchenne muscular dystrophy: A tool for therapeutic development. Neuromuscul Disord. 2015 Nov;25(11):827-34. doi: 10.1016/j.nmd.2015.08.005. Epub 2015 Aug 11.

  PMID: 26365037 BACKGROUND

• Gurvich OL, Maiti B, Weiss RB, Aggarwal G, Howard MT, Flanigan KM. DMD exon 1 truncating point mutations: amelioration of phenotype by alternative translation initiation in exon 6. Hum Mutat. 2009 Apr;30(4):633-40. doi: 10.1002/humu.20913.

  PMID: 19206170 BACKGROUND

• Flanigan KM, Dunn DM, von Niederhausern A, Howard MT, Mendell J, Connolly A, Saunders C, Modrcin A, Dasouki M, Comi GP, Del Bo R, Pickart A, Jacobson R, Finkel R, Medne L, Weiss RB. DMD Trp3X nonsense mutation associated with a founder effect in North American families with mild Becker muscular dystrophy. Neuromuscul Disord. 2009 Nov;19(11):743-8. doi: 10.1016/j.nmd.2009.08.010. Epub 2009 Sep 29.

  PMID: 19793655 BACKGROUND

• Vulin A, Barthelemy I, Goyenvalle A, Thibaud JL, Beley C, Griffith G, Benchaouir R, le Hir M, Unterfinger Y, Lorain S, Dreyfus P, Voit T, Carlier P, Blot S, Garcia L. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping. Mol Ther. 2012 Nov;20(11):2120-33. doi: 10.1038/mt.2012.181. Epub 2012 Sep 11.

  PMID: 22968479 BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

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: Megan Waldrop, Sponsor-Investigator
• Organization: Nationwide Children's Hospital

megan.waldrop@nationwidechildrens.org

614-722-2231

Study Officials

• Megan Waldrop, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: This trial will deliver the minimal efficacious dose as determined by preclinical studies and approved by the FDA to determine safety and target engagement.

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: January 27, 2020
• Study Start: January 15, 2020
• Primary Completion: November 13, 2023
• Study Completion: July 1, 2025
• Last Updated: September 11, 2025
• Results First Posted: September 11, 2025

Record last verified: 2025-08

Locations

US (1)