NCT02376816

Brief Summary

The proposed phase I clinical trial is a pilot study to evaluate safety and biological activity of the rAAVrh74.MCK.micro-Dystrophin vector administered by an intramuscular route. This study will evaluated the micro-Dystrophin vector as a potential dystrophin replacement mechanism for Duchenne Muscular Dystrophy. Two cohorts will undergo gene transfer in a standard three-six dose escalation scheme to establish maximum tolerated dose (MTD) using toxicity. A minimum of three subjects will be enrolled into each cohort. The first cohort will receive a total dose of 3E11 vg. The second cohort will receive 1E12 vg total dose.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
2

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2015

Typical duration 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

First Submitted

Initial submission to the registry

February 26, 2015

Completed
3 days until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 3, 2015

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2017

Completed
Last Updated

November 24, 2017

Status Verified

November 1, 2017

Enrollment Period

2.5 years

First QC Date

February 26, 2015

Last Update Submit

November 21, 2017

Conditions

Duchenne Muscular Dystrophy

Keywords

DMDmuscular dystrophydystrophin

Outcome Measures

Primary Outcomes (1)

  • Safety based on number of participants with adverse events

    AEs will be monitored and scored for severity and relatedness to the study article.

    2 years

Secondary Outcomes (1)

  • Transgene Expression

    180 Days

Study Arms (2)

Cohort 1: Low Dose

EXPERIMENTAL

The rAAVrh74.MCK.micro-Dystrophin vector will be injected to the Extensor Digitorum Brevis (EDB) muscle of a single foot at a total dose of 3E11 vg. The contralateral EDB muscle will injected with normal saline placebo as a comparator. Both physician and study team will be blinded as to which muscle received vector vs placebo. A minimum of three (3) patients with DMD will be enrolled in this cohort.

Biological: rAAVrh74.MCK.micro-Dystrophin

Cohort 2: High Dose

EXPERIMENTAL

The rAAVrh74.MCK.micro-Dystrophin vector will be injected to the Extensor Digitorum Brevis (EDB) muscle of a single foot at a total dose of 1E12 vg. The contralateral EDB muscle will injected with normal saline placebo as a comparator. Both physician and study team will be blinded as to which muscle received vector vs placebo. A minimum of three (3) patients with DMD will be enrolled in this cohort.

Biological: rAAVrh74.MCK.micro-Dystrophin

Interventions

rAAVrh74.MCK.micro-DystrophinBIOLOGICAL

Recombinant adeno-associated virus carrying a truncated "micro" dystrophin transgene under control of a muscle specific MCK promoter.

Cohort 1: Low DoseCohort 2: High Dose

Eligibility Criteria

Age7 Years+
Sexmale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Age 7 or older; must be wheelchair-dependent
  • Confirmed Dystrophin mutations based on mutation compatibility with micro-dys cDNA based on previously published methods.
  • Males of any ethnic group will be eligible.
  • Ability to cooperate with muscle testing.
  • Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception (If appropriate).

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 A, B or C infection
  • Diagnosis of (or ongoing treatment for) an autoimmune disease
  • Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer.
  • Subjects with AAVrh74 binding antibody titers ≥ 1:50 as determined by ELISA immunoassay.
  • Abnormal laboratory values in the clinically significant range as defined in protocol or based upon normal values in the Nationwide Children's Hospital Laboratory.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (3)

  • Rodino-Klapac LR, Montgomery CL, Mendell JR, Chicoine LG. AAV-mediated gene therapy to the isolated limb in rhesus macaques. Methods Mol Biol. 2011;709:287-98. doi: 10.1007/978-1-61737-982-6_19.

    PMID: 21194036BACKGROUND

  • Rodino-Klapac LR, Montgomery CL, Bremer WG, Shontz KM, Malik V, Davis N, Sprinkle S, Campbell KJ, Sahenk Z, Clark KR, Walker CM, Mendell JR, Chicoine LG. Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery. Mol Ther. 2010 Jan;18(1):109-17. doi: 10.1038/mt.2009.254. Epub 2009 Nov 10.

    PMID: 19904237BACKGROUND

  • Rodino-Klapac LR, Janssen PM, Montgomery CL, Coley BD, Chicoine LG, Clark KR, Mendell JR. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy. J Transl Med. 2007 Sep 24;5:45. doi: 10.1186/1479-5876-5-45.

    PMID: 17892583BACKGROUND

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
SPONSOR INVESTIGATOR
PI Title
Director, Center for Gene Therapy

Study Record Dates

First Submitted

February 26, 2015

First Posted

March 3, 2015

Study Start

March 1, 2015

Primary Completion

September 1, 2017

Study Completion

September 1, 2017

Last Updated

November 24, 2017

Record last verified: 2017-11

Locations

US(1)