Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months (LHON)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03428178|
Recruitment Status : Active, not recruiting
First Posted : February 9, 2018
Last Update Posted : July 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: rAAV2-ND4||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||120 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|Official Title:||Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months|
|Actual Study Start Date :||January 8, 2018|
|Actual Primary Completion Date :||December 6, 2018|
|Estimated Study Completion Date :||December 30, 2020|
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.
rAAV2-ND4 of vitreous cavity injection
Other Name: rAAV2-ND4 gene therapy
- BCVA [ Time Frame: Change from Baseline at 12 months ]The Best Corrected Visual Acuity
- Computerized Visual Field [ Time Frame: Change from Baseline at 12 months ]Visual Field index
- Computerized Visual Field [ Time Frame: Change from Baseline at 12 months ]Mean Defect
- VEP [ Time Frame: Change from Baseline at 12 months ]visual evoked potential
- RNFL [ Time Frame: Change from Baseline at 12 months ]retinal nerve fiber layer
- Liver function in plasma [ Time Frame: Before treatment and in the first ,third,sixth,twelfth month after the treatment ]Before and after the treatment,Liver function in plasma will be checked.
- kidney function in plasma [ Time Frame: Before treatment and in the first ,third,sixth,twelfth month after the treatment ]Before and after the treatment,kidney function in plasma will be checked.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03428178
|Department of Ophthalmology ，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology|
|Wuhan, Hubei, China, 430030|