NCT00428935

Brief Summary

The purpose of this study is to determine the safety of a miniature dystrophin gene in the treatment of progressive muscle weakness due to Duchenne Muscular Dystrophy (DMD).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2006

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2006

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

January 26, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 30, 2007

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2009

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2010

Completed
Last Updated

February 5, 2013

Status Verified

February 1, 2013

Enrollment Period

3 years

First QC Date

January 26, 2007

Last Update Submit

February 4, 2013

Conditions

Duchenne Muscular Dystrophy

Keywords

DuchenneMuscleMuscular DystrophyGene TherapyDystrophinAdeno-Associated VirusAAV

Outcome Measures

Primary Outcomes (1)

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Physical Exams assessing major organ systems and safety labs (GGT, Bilirubin, Glucose, Amylase, CBC/Diff, AFP, Platelets, PT/PTT, Creatinine, Electrolytes, Total protein, Alkaline phosphatase, and Urinalysis)

    followed for 2 years post injection

Secondary Outcomes (2)

  • mini-dystrophin gene expression at the site of gene transfer

    90 days post injection

  • Maximal Volume Isometric Contraction Testing as a measure of muscle strength

    out to 2 years post injection

Study Arms (2)

Low Dose

EXPERIMENTAL

Low dose cohort - 2.0E10 vg/kg

Biological: rAAV2.5-CMV-minidystrophin (d3990)

High Dose

EXPERIMENTAL

High Dose - 1.0E11 vg/kg

Biological: rAAV2.5-CMV-minidystrophin (d3990)

Interventions

rAAV2.5-CMV-minidystrophin (d3990)BIOLOGICAL

Recombinant adeno-associated virus (AAV) carrying a truncated human dystrophin gene (mini-dystrophin) expressed from a cytomegalovirus (CMV) promoter.

High DoseLow Dose

Eligibility Criteria

Age5 Years - 15 Years
Sexmale
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Known null mutation of the Dystrophin gene
  • Male age of 5 years or older
  • If taking corticosteroids, must have dose unchanged for the past 3 months
  • Serum creatine kinase elevation greater than 10x normal value (established by Children's Hospital)
  • Progressive, symmetrical proximal muscle weakness of arms and legs

You may not qualify if:

  • Unable to cooperate for muscle strength testing
  • Joint contractures that prohibit muscle strength testing
  • Concomitant illness
  • Individuals predisposed to excessive vagal responses (bradyarrhythmia or hypotension)
  • Controlled substance abuse

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Columbus Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (4)

  • Watchko J, O'Day T, Wang B, Zhou L, Tang Y, Li J, Xiao X. Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Hum Gene Ther. 2002 Aug 10;13(12):1451-60. doi: 10.1089/10430340260185085.

    PMID: 12215266BACKGROUND

  • Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13714-9. doi: 10.1073/pnas.240335297.

    PMID: 11095710BACKGROUND

  • Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C, Lewis S, Bowles D, Gray S, Li C, Galloway G, Malik V, Coley B, Clark KR, Li J, Xiao X, Samulski J, McPhee SW, Samulski RJ, Walker CM. Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med. 2010 Oct 7;363(15):1429-37. doi: 10.1056/NEJMoa1000228.

    PMID: 20925545RESULT

  • Bowles DE, McPhee SW, Li C, Gray SJ, Samulski JJ, Camp AS, Li J, Wang B, Monahan PE, Rabinowitz JE, Grieger JC, Govindasamy L, Agbandje-McKenna M, Xiao X, Samulski RJ. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther. 2012 Feb;20(2):443-55. doi: 10.1038/mt.2011.237. Epub 2011 Nov 8.

    PMID: 22068425RESULT

Related Links

MeSH Terms

Conditions

Muscular Dystrophy, DuchenneMuscular Dystrophies

Condition Hierarchy (Ancestors)

Muscular Disorders, AtrophicMuscular DiseasesMusculoskeletal DiseasesNeuromuscular DiseasesNervous System DiseasesGenetic Diseases, X-LinkedGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

  • Jerry R. Mendell, MD

    Nationwide Children's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director Center for Gene Therapy

Study Record Dates

First Submitted

January 26, 2007

First Posted

January 30, 2007

Study Start

March 1, 2006

Primary Completion

March 1, 2009

Study Completion

July 1, 2010

Last Updated

February 5, 2013

Record last verified: 2013-02

Locations

US(1)