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

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

Detailed Description
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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.

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

Conditions
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Leber Hereditary Optic Neuropathy

Intervention / Treatment
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* Drug: rAAV2-ND4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: comply with Leber hereditary optic neuropathy diagnostic criteria. in patients with informed consent, voluntary participation. signed informed consent. 8 ≤ Age ≤ 60 years old, good health, the patient can tolerate local anesthesia surgery. to comply with doctor's instructions, can in the time of referral. Exclusion Criteria: 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. Are participating in other clinical studies of patients. Patients with mental disorders.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rAAV2-ND4<br>injection | Drug: rAAV2-ND4<br>* injection<br>* Other names: rAAV2-ND4 gene therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Best Corrected Visual Acuity(BCVA) |  | Up to 3 years | 
| Results of CD3/CD4/CD8 Test | The mean percentage of CD3+/CD4+/CD8+ test before and after treatment | up to 6 months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leber's Hereditary Optic Neuropathy,11778 LHON mutation,, rAAV2-ND4,triamcinolone acetonide