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

Not Applicable

Completed

• Conditions: Leber Hereditary Optic Neuropathy
• Interventions: Drug: rAAV2-ND4

• Registration Number: NCT01267422
• Lead Sponsor: Bin Li

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 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.

Study Timeline

• Study First Submitted: 2010-12-27
• Study First Submitted QC: 2010-12-27
• Study First Posted: 2010-12-28
• Study Start: 2011-04
• Results First Submitted: 2015-05-21
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Results First Submitted QC: 2016-03-29
• Results First Posted: 2016-05-02
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-07
• Last Update Posted: 2018-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
rAAV2-ND4	rAAV2-ND4	injection

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Intraocular Pressure;	Up to 3 years
Average RNFL Thickness Througth Optical Coherence Tomography(OCT) Test	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)	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)	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.
Neutralizing Antibody Assay	up to 3 years	The mean of Neutralizing antibody assay of 8 patients before and after treatment

Trial Locations

Locations (1)

Department of Ophthalmology ，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China