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Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months (LHON)

Primary Purpose

Acute LHON, Onset Within Three Months, Onset Between 3 to 6 Months

Status

Unknown status

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

rAAV2-ND4

About this trial

This is an interventional treatment trial for Acute LHON focused on measuring Acute LHON, onset within three months, onset between 3 to 6 months, onset between 6 to 12 months, onset between 12 to 24 months, onset between 24 to 60 months, onset over 60 months

Eligibility Criteria

8 Years - 60 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Patients carry the mitochondrial point mutation at 11778, which is consistent with the diagnostic criteria for LHON.
The vision falls within 3 months,onset between 3 to 6 months,onset between 6 to 12 months,onset between 12 to 24 months,onset between 24 to 60 months,and onset over 60 months.
Patients signed written informed consent.
Patients are between the ages of 8 and 60 years old and able to tolerate the gene therapy procedure which includes local anesthesia.
Patients are willing to follow the doctor's instructions and to consult the doctor at prescribed times.
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:

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.
Patients who are participating in other clinical studies are excluded.
Patients who suffer from a diagnosed mental problem are excluded.
Patients who suffer from chronic diseases such as diabetes and hypertension are excluded.
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.

Sites / Locations

Department of Ophthalmology ，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

rAAV2-ND4

Arm Description

A Single IVT 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.

Outcomes

Primary Outcome Measures

BCVA

The Best Corrected Visual Acuity

Secondary Outcome Measures

Computerized Visual Field

Visual Field index

Computerized Visual Field

Mean Defect

VEP

visual evoked potential

RNFL

retinal nerve fiber layer

Liver function in plasma

Before and after the treatment,Liver function in plasma will be checked.

kidney function in plasma

Before and after the treatment,kidney function in plasma will be checked.

Full Information

NCT ID

NCT03428178

First Posted

January 7, 2018

Last Updated

July 27, 2020

Sponsor

Bin Li

1. Study Identification

Unique Protocol Identification Number

NCT03428178

Brief Title

Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months

Acronym

LHON

Official Title

Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Unknown status

Study Start Date

January 8, 2018 (Actual)

Primary Completion Date

December 6, 2018 (Actual)

Study Completion Date

December 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Bin Li

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Efficacy Study of Gene Therapy for The Treatment of Acute Leber's Hereditary Optic Neuropathy (LHON) onset within three months

Detailed Description

Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited ocular disorder associated with a mutation in mtDNA .The disease is a common cause of teenaged blindness in both eyes for which there is currently no effective treatment. In 2008, the investigators recognized that gene therapy for LHON could be performed not only theoretically but technically. The investigators have been carring out a series of basic and clinical studies from constructing the vectors to identifying and mitigating safety issues . After performing several animal experiments, the investigators had moved into clinical trials. In 2011, the investigators performed the first LHON gene therapy trial in the world, which was registered in December 2010 at ClinicalTrials.gov (Registration number: CT01267422) and was a preliminary study to verify the safety and efficacy of gene therapy for LHON . In the 36-month follow-up, the investigators found that six out of nine patients have vision improvement obviously and no adverse events were observed. This is a multi - center , prospective study of 120 patients with the G11778A mutation in Mt-DNA.This clinical trial recruited 20 patients with the 11778 mutation of MT-DNA onset within three months,20 between 3 to 6 months,20 between 6 to 12 months,20 between 12 to 24 months,20 between 24 to 60 months,and 20 over 60 months.. All patients will be treated with a Single vitreous cavity injection of recombinant Adeno-Associated Virus-NADH dehydrogenase, subunit 4 (complex I)（rAAV2-ND4)（0.05ml), with dose 1 × 10^10 vg/0.05 mL .The eye of treatment is up to the time of onset. The visual acuity, visual field,visual evoked potential （VEP）,optical coherence tomography（ OCT）, electroretinograms(ERG), retinal nerve fiber layer(RNFL)and Liver and kidney function in plasma were compared after treatment at 1,2,3,6and 12 months interval.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute LHON, Onset Within Three Months, Onset Between 3 to 6 Months, Onset Between 6 to 12 Months, Onset Between 12 to 24 Months, Onset Between 24 to 60 Months, Onset Over 60 Months

Keywords

Acute LHON, onset within three months, onset between 3 to 6 months, onset between 6 to 12 months, onset between 12 to 24 months, onset between 24 to 60 months, onset over 60 months

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

20 patients of Leber Hereditary Optic Neuropathy (LHON) onset within 3 months,20 between 3 to 6 months,20 between 6 to 12 months,20 between 12 to 24 months,20 between 24 to 60 months,and 20 over 24 months.

Masking

None (Open Label)

Allocation

N/A

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

rAAV2-ND4

Arm Type

Experimental

Arm Description

A Single IVT 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.

Intervention Type

Drug

Intervention Name(s)

rAAV2-ND4

Other Intervention Name(s)

rAAV2-ND4 gene therapy

Intervention Description

rAAV2-ND4 of vitreous cavity injection

Primary Outcome Measure Information:

Title

BCVA

Description

The Best Corrected Visual Acuity

Time Frame

Change from Baseline at 12 months

Secondary Outcome Measure Information:

Title

Computerized Visual Field

Description

Visual Field index

Time Frame

Change from Baseline at 12 months

Title

Computerized Visual Field

Description

Mean Defect

Time Frame

Change from Baseline at 12 months

Title

VEP

Description

visual evoked potential

Time Frame

Change from Baseline at 12 months

Title

RNFL

Description

retinal nerve fiber layer

Time Frame

Change from Baseline at 12 months

Title

Liver function in plasma

Description

Before and after the treatment,Liver function in plasma will be checked.

Time Frame

Before treatment and in the first ,third,sixth,twelfth month after the treatment

Title

kidney function in plasma

Description

Before and after the treatment,kidney function in plasma will be checked.

Time Frame

Before treatment and in the first ,third,sixth,twelfth month after the treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients carry the mitochondrial point mutation at 11778, which is consistent with the diagnostic criteria for LHON. The vision falls within 3 months,onset between 3 to 6 months,onset between 6 to 12 months,onset between 12 to 24 months,onset between 24 to 60 months,and onset over 60 months. Patients signed written informed consent. Patients are between the ages of 8 and 60 years old and able to tolerate the gene therapy procedure which includes local anesthesia. Patients are willing to follow the doctor's instructions and to consult the doctor at prescribed times. 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: 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. Patients who are participating in other clinical studies are excluded. Patients who suffer from a diagnosed mental problem are excluded. Patients who suffer from chronic diseases such as diabetes and hypertension are excluded. 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.

Facility Information:

Facility Name

Department of Ophthalmology ，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

City

Wuhan

State/Province

Hubei

ZIP/Postal Code

430030

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

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Citation

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Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months

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