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

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ClinicalTrials.gov Identifier: NCT03428178
Recruitment Status : Recruiting
First Posted : February 9, 2018
Last Update Posted : February 28, 2019
Sponsor:
Information provided by (Responsible Party):
Bin Li, Huazhong University of Science and Technology

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

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

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.


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Study Type : Interventional  (Clinical Trial)
Estimated 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)
Primary Purpose: Treatment
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 : January 30, 2018
Estimated Study Completion Date : January 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: rAAV2-ND4
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.
Drug: rAAV2-ND4
rAAV2-ND4 of vitreous cavity injection
Other Name: rAAV2-ND4 gene therapy




Primary Outcome Measures :
  1. BCVA [ Time Frame: Change from Baseline at 12 months ]
    The Best Corrected Visual Acuity


Secondary Outcome Measures :
  1. Computerized Visual Field [ Time Frame: Change from Baseline at 12 months ]
    Visual Field index

  2. Computerized Visual Field [ Time Frame: Change from Baseline at 12 months ]
    Mean Defect

  3. VEP [ Time Frame: Change from Baseline at 12 months ]
    visual evoked potential

  4. RNFL [ Time Frame: Change from Baseline at 12 months ]
    retinal nerve fiber layer

  5. 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.

  6. 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.



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Ages Eligible for Study:   8 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Patients carry the mitochondrial point mutation at 11778, which is consistent with the diagnostic criteria for LHON.
  2. 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.
  3. Patients signed written informed consent.
  4. Patients are between the ages of 8 and 60 years old and able to tolerate the gene therapy procedure which includes local anesthesia.
  5. Patients are willing to follow the doctor's instructions and to consult the doctor at prescribed times.
  6. 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.

Information from the National Library of Medicine

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


Contacts
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Contact: Bin Li, PhD,MD 8613638673626 libin-12@163.com
Contact: Jiajia Yuan, MD 8617187182165 yuanjj911@163.com

Locations
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China, Hubei
Department of Ophthalmology ,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China, 430030
Contact: Bin Li, PhD,MD    8613638673626    libin-12@163.com   
Contact: Jiajia Yuan, MD    8617187182165    yuanjj911@163.com   
Sponsors and Collaborators
Bin Li

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bin Li, Clinical Professor, Huazhong University of Science and Technology
ClinicalTrials.gov Identifier: NCT03428178     History of Changes
Other Study ID Numbers: LHON(Acute)
First Posted: February 9, 2018    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bin Li, Huazhong University of Science and Technology:
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
Additional relevant MeSH terms:
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Optic Atrophy, Hereditary, Leber
Optic Atrophies, Hereditary
Optic Atrophy
Optic Nerve Diseases
Cranial Nerve Diseases
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Eye Diseases, Hereditary
Eye Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases