Clinical Trial: Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: Phase I Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2

Brief Summary: The proposed clinical trial study of rAAVrh74.MCK.GALGT2 for duchenne muscular dystrophy (DMD) patients that will involve direct intramuscular injection to the extensor digitorum brevis muscle (EDB).

Detailed Summary: This is a phase I safety and tolerability study. Three DMD subjects will receive bilateral injections into the EDB muscle, with one EDB receiving the GALGT2 vector (rAAVrh74.MCK.GALGT2) and the other side receiving saline alone (assigned in a randomized fashion). Three subjects will receive a single gene transfer dose of 1E12 vector genomes, and patients and investigators will be blinded as to which muscle is injected with vector. Muscle biopsies will be performed at three months (12 weeks) in two subjects and at 1.5 months (6 weeks) in one subject and evaluated blindly for the expression of the GALGT2 transgene.
Sponsor: Kevin Flanigan

Current Primary Outcome: Treatment related toxicities [ Time Frame: 2 years ]

Based on the development of unacceptable toxicity defined as the occurrence of any one Grade III or higher treatment-related toxicities.


Original Primary Outcome: Treatment related toxicities [ Time Frame: 2 years ]

Based on the development of unacceptable toxicity defined as the occurrence of any one Grade III or higher treatment-related toxicities, or two or more Grade II treatment-related toxicities.


Current Secondary Outcome:

  • Expression of GALGT2 demonstrated with anti-CT epitope antibodies. [ Time Frame: 6 or 12 weeks ]
  • GALGT2 protein expression quantified by western blot and assessed by densitometry [ Time Frame: 6 or 12 weeks ]
  • Transduction efficiency measured by qPCR of the GALGT transgene from muscle, and expressed as vector genomes normalized to a genomic single-copy control. [ Time Frame: 6 or 12 weeks ]
  • Number of fibers containing central nuclei compared between muscles by paired t-tests [ Time Frame: 6 or 12 weeks ]
  • Dystrophin expression demonstrated with antibodies to N-terminal, C-terminal, and rod domains [ Time Frame: 6 or 12 weeks ]
  • Utrophin expression [ Time Frame: 6 or 12 weeks ]
  • Leukocyte markers including CD45, CD3, CD4, CD8, and MAC 387 [ Time Frame: 6 or 12 weeks ]
  • Muscle will be examined for histological appearance [ Time Frame: 6 or 12 weeks ]
  • Antibodies to rAAVrh74 along with PBMC ELISpots to both rAAVrh74 capsid and GALGT protein will be evaluated at different time points during the study [ Time Frame: 6 or 12 weeks ]


Original Secondary Outcome:

  • Expression of GALGT2 demonstrated with anti-CT epitope antibodies. [ Time Frame: 2 years ]
  • GALGT2 protein expression quantified by western blot and assessed by densitometry [ Time Frame: 2 years ]
  • Transduction efficiency measured by qPCR of the GALGT transgene from muscle, and expressed as vector genomes normalized to a genomic single-copy control. [ Time Frame: 2 years ]
  • Number of fibers containing central nuclei compared between muscles by paired t-tests [ Time Frame: 2 years ]
  • Dystrophin expression demonstrated with antibodies to N-terminal, C-terminal, and rod domains [ Time Frame: 2 years ]
  • Utrophin expression [ Time Frame: 2 years ]
  • Leukocyte markers including CD45, CD3, CD4, CD8, and MAC 387 [ Time Frame: 2 years ]
  • Muscle will be examined for histological appearance [ Time Frame: 2 years ]
  • Antibodies to rAAVrh74 along with PBMC ELISpots to both rAAVrh74 capsid and GALGT protein will be evaluated at different time points during the study [ Time Frame: 2 years ]
  • The muscle analysis of gene expression and inflammation will also be done without breaking the blind. [ Time Frame: 2 years ]


Information By: Nationwide Children's Hospital

Dates:
Date Received: December 23, 2015
Date Started: April 2016
Date Completion: February 2020
Last Updated: November 4, 2016
Last Verified: November 2016