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

This study has been completed.
Huazhong University of Science and Technology
Information provided by (Responsible Party):
Bin Li, Huazhong University of Science and Technology Identifier:
First received: December 27, 2010
Last updated: March 29, 2016
Last verified: March 2016
This study is meant to assess the safety and efficacy of rAAV2-ND4 treatment of Leber hereditary optic neuropathy with 11778 LHON mutation.

Condition Intervention
Leber Hereditary Optic Neuropathy
Drug: rAAV2-ND4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy

Resource links provided by NLM:

Further study details as provided by Huazhong University of Science and Technology:

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

Secondary Outcome Measures:
  • Intraocular Pressure; [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Neutralizing Antibody Assay [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    VFI: visual field index ,the value Close to 100% regarded normal. VFI/MD:The bigger one was more close to the normal value.

Enrollment: 9
Study Start Date: April 2011
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rAAV2-ND4
Drug: rAAV2-ND4
Other Name: rAAV2-ND4 gene therapy

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.


Ages Eligible for Study:   8 Years to 60 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01267422

China, Hubei
Department of Ophthalmology ,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wu Han, Hubei, China, 430030
Sponsors and Collaborators
Bin Li
Huazhong University of Science and Technology
Study Chair: bin Li, PhD,MD Deputy Director of Ophthalmology
  More Information


Responsible Party: Bin Li, Safety and Efficacy Study of rAAV2-ND4 Treatment of LHON, Huazhong University of Science and Technology Identifier: NCT01267422     History of Changes
Other Study ID Numbers: RAVCT-2 
Study First Received: December 27, 2010
Results First Received: May 21, 2015
Last Updated: March 29, 2016
Health Authority: China: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Huazhong University of Science and Technology:
Leber's Hereditary Optic Neuropathy,11778 LHON mutation,
rAAV2-ND4,triamcinolone acetonide

Additional relevant MeSH terms:
Optic Atrophy, Hereditary, Leber
Optic Atrophies, Hereditary
Eye Diseases, Hereditary
Peripheral Nervous System Diseases
Optic Nerve Diseases
Neuromuscular Diseases
Nervous System Diseases
Cranial Nerve Diseases
Eye Diseases
Optic Atrophy
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases processed this record on October 21, 2016