Clinical Trial: Safety and Efficacy Study of Gene Therapy for The Treatment of Leber's Hereditary Optic Neuropathy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Safety and Efficacy Study of Gene Therapy for The Treatment of Leber's Hereditary Optic Neuropathy

Brief Summary: This study is meant to evaluate the safety and efficacy of rAAV2-ND4 treatment for Leber hereditary optic neuropathy with the G11778A mutation in mitochondrial DNA.

Detailed Summary:

Leber's Optic Hereditary Neuropathy (LHON) is a maternally inherited ocular disorder associated with a mutation in mtDNA .The disease is a common cause of teenaged blindness in both eyes for which there is currently no effective treatment.

In 2008, the investigators recognized that gene therapy for LHON could be performed not only theoretically but technically. the investigators have been carring out a series of basic and clinical studies from constructing the vectors to identifying and mitigating safety issues . After performing several animal experiments, the investigators had moved into clinical trials. In 2011, the investigators performed the first LHON gene therapy trial in the world, which was registered in December 2010 at ClinicalTrials.gov (Registration number: CT01267422) and was a preliminary study to verify the safety and efficacy of gene therapy for LHON . In the 36-month follow-up, the investigators found that six out of nine patients have different degrees of vision improvement and no adverse events were observed.

This is a multi - center, randomized, double - blind study of 48 patients with the G11778A mutation in MtDNA.The patients were included, of which 24 were at more than 24 months after onset , and 24 were less than 24 months。24 patients with shorter course were randomly divided into two groups (the first group, the second group), each group has 12 people, the first group is treated with a Single IVT Injection of recombinant Adeno-Associated Virus-NADH dehydrogenase, subunit 4 (complex I)（rAAV2-ND4)（0.05ml), the dose is 1 × 10^10 vg/0.05 mL for them.The second group is treated with normal saline（0.05ml); 24 patients with longer course were randomly divided into two groups (grouped into the third group, the fourth group), each group has 12 people, the third group is tre
Sponsor: Huazhong University of Science and Technology

Current Primary Outcome:

  • BCVA [ Time Frame: Change from Baseline at 12 months . ]
    The Best Corrected Visual Acuity
  • Computerized Visual Field [ Time Frame: Change from Baseline at 12 months . ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • VEP [ Time Frame: Change from Baseline at 12 months . ]
    visual evoked potential
  • RNFL [ Time Frame: Change from Baseline at 12 months . ]
    retinal nerve fiber layer
  • Liver function in plasma [ Time Frame: Change from Baseline at 12 months . ]
  • kidney function in plasma [ Time Frame: Change from Baseline at 12 months . ]


Original Secondary Outcome: Same as current

Information By: Huazhong University of Science and Technology

Dates:
Date Received: May 10, 2017
Date Started: September 1, 2017
Date Completion: June 30, 2019
Last Updated: May 18, 2017
Last Verified: May 2017