A Single Intravitreal Injection of rAAV2-ND4 for the Treatment of Leber's Hereditary Optic Neuropathy

September 15, 2020 updated by: Bin Li, Huazhong University of Science and Technology
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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Leber's Optic Hereditary Neuropathy (LHON) is a maternally inherited ocular disorder primarily associated with mutations in mitochondrial DNA. The disease is a common cause of blindness in both eyes of affected teenagers and young adults. There is currently no approved effective treatment for LHON.

In 2011, the first LHON gene therapy investigator-initiated study was conducted (registered in December 2010 with ClinicalTrials.gov Identifier NCT01267422) to explore the safety and efficacy of gene therapy for LHON. The gene therapy was a recombinant adeno-associated virus serotype 2 containing human mitochondrial ND4 (MT-ND4) gene (rAAV2-ND4). By 36 months of follow-up, six out of nine patients who received the rAAV2-ND4 intravitreal injection experienced clinically significant vision improvement and no adverse events were observed.

This is an open-label, single-arm, multi-center study to further evaluate the safety and efficacy of rAAV-ND4 in the treatment of LHON patients with G11778A mutation. All patients will be treated with a single intravitreal injection rAAV-ND4, with dose 1 × 10^10 vg/0.05 mL in one of the eyes.

Study Type

Interventional

Enrollment (Actual)

159

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Department of Ophthalmology,Tongji Hospital, Tongji Medical College, Huazhong University of science and Technology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients carry the mitochondrial point mutation at 11778, which is consistent with the diagnostic criteria for LHON.
  2. No apparent eye sight improvement in LHON patients or any other treatment within the past year.
  3. Eyesight of both eyes is below 0.3.
  4. Patients signed written informed consent.
  5. Patients are between the ages of 10 and 65 years old and able to tolerate the gene therapy procedure which includes local anesthesia.
  6. Patients are willing to follow the doctor's instructions and to consult the doctor at prescribed times.
  7. Patient's physical examination results are all normal, including liver function, kidney function, routine blood test, routine urine test, complete immunological test, and humoral immune response.

Exclusion Criteria:

  1. Patients who are wearing a cardiac pacemaker, suffering from severe heart, lung or kidney function failure, various hemorrhagic diseases, acute infectious diseases, high fever, or convalescing after heart surgery or who are pregnant are excluded.
  2. Patients who are participating in other clinical studies are excluded.
  3. Patients who suffer from a diagnosed mental problem are excluded.
  4. Patients who suffer from chronic diseases such as diabetes and hypertension are excluded.
  5. Patients who show abnormal test results such as positive AAV2 humoral immune response (positive means that the AAV2 neutralizing antibody assay of patient was significant different when comparing free serum with 1:20 serum concentrations) and abnormal human T lymphocyte subsets CD3+, CD3+/CD4+ and CD3+/CD8+ prior to gene therapy surgery are excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: rAAV2-ND4
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 test groups.
Drug: rAAV2-ND4
a Single IVT Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
BCVA
Time Frame: Change from Baseline at 12 months .
The Best Corrected Visual Acuity
Change from Baseline at 12 months .
Computerized Visual Field
Time Frame: Change from Baseline at 12 months .
Change from Baseline at 12 months .

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Huazhong University of Science and Technology

Collaborators

Shiyan Taihe Hospital

Investigators

  • Study Chair: Bin Li, PhD,MD, Deputy Director of Ophthalmology,Tongji Hospital
  • Principal Investigator: Yong Zhang, PhD,MD, Director of Ophthalmology，Shiyan Taihe Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 27, 2017

Primary Completion (Actual)

January 15, 2020

Study Completion (Anticipated)

January 15, 2025

Study Registration Dates

First Submitted

May 10, 2017

First Submitted That Met QC Criteria

May 12, 2017

First Posted (Actual)

May 15, 2017

Study Record Updates

Last Update Posted (Actual)

September 17, 2020

Last Update Submitted That Met QC Criteria

September 15, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Leber 2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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