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

• Sponsor: Huazhong University of Science and Technology (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03153293
• Collaborator: Shiyan Taihe Hospital (Other)
• Enrollment: 159
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 84.6
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leber Hereditary Optic Neuropathy	Drug: rAAV2-ND4	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 159 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Intravitreal Injection of rAAV2-ND4 for the Treatment of Leber's Hereditary Optic Neuropathy
• Actual Study Start Date: Dec 27, 2017
• Actual Primary Completion Date: Jan 15, 2020
• Anticipated Study Completion Date: Jan 15, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. BCVA [Change from Baseline at 12 months .]

   The Best Corrected Visual Acuity

2. Computerized Visual Field [Change from Baseline at 12 months .]

Secondary Outcome Measures

1. VEP [Change from Baseline at 12 months .]

   visual evoked potential

2. RNFL [Change from Baseline at 12 months .]

   retinal nerve fiber layer

3. Liver function in plasma [Change from Baseline at 12 months .]

4. kidney function in plasma [Change from Baseline at 12 months .]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Ophthalmology，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei	China	430030

Sponsors and Collaborators

• Huazhong University of Science and Technology
• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bin Li, professor, Huazhong University of Science and Technology
• ClinicalTrials.gov Identifier: NCT03153293
• Other Study ID Numbers: Leber 2
• First Posted: May 15, 2017
• Last Update Posted: Sep 17, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bin Li, professor, Huazhong University of Science and Technology: LHON,G11778A mutation, rAAV2-ND4，gene therapy
• Additional relevant MeSH terms: Optic Nerve Diseases; Optic Atrophy, Hereditary, Leber

Study Results

No Results Posted as of Sep 17, 2020