Clinical Trial: Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy

Brief Summary: This study is meant to assess the safety and efficacy of rAAV2-ND4 treatment of Leber hereditary optic neuropathy with 11778 LHON mutation.

Detailed Summary:

Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited ocular disorder associated with a mutation in mtDNA . The common manifestation is visual loss which caused by the respiratory chain enzymes complex dysfunction resulting in increased oxidative stress enzymes production.

Material and Method Seven patients with 11778 LHON mutation were randomly treated with a Single IVT Injection of recombinant Adeno-Associated Virus-NADH dehydrogenase, subunit 4 (complex I)（rAAV2-ND4)（0.05ml).The dose was 5 × 10^9 vg/0.05 mL for patients younger than 12 years old, and 1 × 10^10 vg/0.05 mL for patients older than 12 years old. The visual acuity, visual evoked potential （VEP）,optical coherence tomography（ OCT）, computerized visual field, electroretinograms(ERG), retinal nerve fiber layer(RNFL)and Liver and kidney function in plasma were compared before and after treatment at 1,3,and 6, months interval.


Sponsor: Bin Li

Current Primary Outcome:

  • The Best Corrected Visual Acuity(BCVA) [ Time Frame: Up to 3 years ]
  • Results of CD3/CD4/CD8 Test [ Time Frame: up to 6 months ]
    The mean percentage of CD3+/CD4+/CD8+ test before and after treatment


Original Primary Outcome: The visual acuity [ Time Frame: 6 month ]

Vision testing before and after treatment


Current Secondary Outcome:

  • Intraocular Pressure; [ Time Frame: Up to 3 years ]
  • Neutralizing Antibody Assay [ Time Frame: up to 3 years ]
    The mean of Neutralizing antibody assay of 8 patients before and after treatment
  • Average RNFL Thickness Througth Optical Coherence Tomography(OCT) Test [ Time Frame: Up to 3 years ]
    Average RNFL thickness of 8 patients througth Optical coherence tomography(OCT) test before and after treatment
  • Computerized Visual Field(MD: Mean Deviation, the Value Close to 0 Regarded Normal) [ Time Frame: up to 3 years ]
    MD: mean deviation, the value Close to 0 regarded normal.VFI/MD：The bigger one was more close to the normal value.
  • Computerized Visual Field(VFI: Visual Field Index ,the Value Close to 100% Regarded Normal) [ Time Frame: up to 3 years ]
    VFI: visual field index ,the value Close to 100% regarded normal. VFI/MD：The bigger one was more close to the normal value.


Original Secondary Outcome:

  • Intraocular pressure [ Time Frame: 6 month ]
    Intraocular pressure testing before and after treatment
  • VEP [ Time Frame: 6 month ]
    VEP testing before and after treatment
  • computerized visual field [ Time Frame: 6 month ]
    computerized visual field testing before and after treatment
  • OCT [ Time Frame: 6 month ]
    OCT testing before and after treatment
  • ERG [ Time Frame: 6 month ]
    ERG testing before and after treatment
  • Liver and kidney function in plasma [ Time Frame: 6 month ]
    Liver and kidney function in plasma testing before and after treatment
  • ELISA [ Time Frame: 6 month ]
    Antibodies against AAV2 capsid was analyzed by ELISA using serum samples collected before injection and different time points after the injection.


Information By: Huazhong University of Science and Technology

Dates:
Date Received: December 27, 2010
Date Started: April 2011
Date Completion:
Last Updated: March 29, 2016
Last Verified: March 2016