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

Overview

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

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2015

Detailed Description

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.

Interventions

  • Drug: rAAV2-ND4
    • injection

Arms, Groups and Cohorts

  • Experimental: rAAV2-ND4
    • injection

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • 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.

Participating in This Clinical Trial

Inclusion Criteria

1. comply with Leber hereditary optic neuropathy diagnostic criteria. 2. in patients with informed consent, voluntary participation. 3. signed informed consent. 4. 8 ≤ Age ≤ 60 years old, good health, the patient can tolerate local anesthesia surgery. 5. to comply with doctor's instructions, can in the time of referral. Exclusion Criteria:

1. Cardiopulmonary and renal function in severe weakness, cancer, a variety of bleeding disorders, acute sensing disease, high fever, high fever disease, women during pregnancy, heart disease, such as post-operative recovery period. 2. Are participating in other clinical studies of patients. 3. Patients with mental disorders.

Gender Eligibility: All

Minimum Age: 8 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Bin Li
  • Collaborator
    • Huazhong University of Science and Technology
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Bin Li, Safety and Efficacy Study of rAAV2-ND4 Treatment of LHON – Huazhong University of Science and Technology
  • Overall Official(s)
    • bin Li, PhD,MD, Study Chair, Deputy Director of Ophthalmology

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Citations Reporting on Results

Wan X, Pei H, Zhao MJ, Yang S, Hu WK, He H, Ma SQ, Zhang G, Dong XY, Chen C, Wang DW, Li B. Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy. Sci Rep. 2016 Feb 19;6:21587. doi: 10.1038/srep21587.

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