Clinical Intramuscular Gene Transfer Trial of rAAVrh74.MCK.Micro-Dystrophin to Patients With Duchenne Muscular Dystrophy

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.

Timeline

Start

2015-03

Primary completion

2017-09

Completion

2017-09

Publications

• Background 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.
• Background 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.
• Background 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.

Drugs

Indications