Safety and Efficacy Study of Gene Therapy for The Treatment of Leber's Hereditary Optic Neuropathy
|ClinicalTrials.gov Identifier: NCT03153293|
Recruitment Status : Active, not recruiting
First Posted : May 15, 2017
Last Update Posted : February 28, 2019
|Condition or disease||Intervention/treatment||Phase|
|Leber Hereditary Optic Neuropathy||Drug: rAAV2-ND4||Phase 2 Phase 3|
Leber's Optic Hereditary 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 different degrees of vision improvement and no adverse events were observed.
This is a multi - center , prospective study of 142 patients with the G11778A mutation in Mt-DNA . The patients were included, of which 69 were at more than 24 months after onset , and 73 were less than 24 months . All patients will be treated with a Single IVT 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 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 before and after treatment at 1,2,3,6and 12 months interval.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||142 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Efficacy Study of Gene Therapy for The Treatment of Leber's Hereditary Optic Neuropathy|
|Actual Study Start Date :||December 27, 2017|
|Estimated Primary Completion Date :||June 30, 2019|
|Estimated Study Completion Date :||June 30, 2019|
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.
a Single IVT Injection
- 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 . ]
- 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: Change from Baseline at 12 months . ]
- kidney function in plasma [ Time Frame: Change from Baseline at 12 months . ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03153293
|Department of Ophthalmology，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology|
|Wuhan, Hubei, China, 430030|
|Study Chair:||Bin Li, PhD,MD||Deputy Director of Ophthalmology,Tongji Hospital|
|Principal Investigator:||Yong Zhang, PhD,MD||Director of Ophthalmology，Shiyan Taihe Hospital|