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Trial record 2 of 29 for:    "Leber hereditary optic neuropathy"

Safety and Efficacy Study of Gene Therapy for The Treatment of Leber's Hereditary Optic Neuropathy

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ClinicalTrials.gov Identifier: NCT03153293
Recruitment Status : Active, not recruiting
First Posted : May 15, 2017
Last Update Posted : February 28, 2019
Sponsor:
Collaborator:
Shiyan Taihe Hospital
Information provided by (Responsible Party):
Bin Li, Huazhong University of Science and Technology

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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 142 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


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




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

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

Secondary Outcome Measures :
  1. VEP [ Time Frame: Change from Baseline at 12 months . ]
    visual evoked potential

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

  3. Liver function in plasma [ Time Frame: Change from Baseline at 12 months . ]
  4. kidney function in plasma [ Time Frame: Change from Baseline at 12 months . ]


Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03153293


Locations
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China, Hubei
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
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Study Chair: Bin Li, PhD,MD Deputy Director of Ophthalmology,Tongji Hospital
Principal Investigator: Yong Zhang, PhD,MD Director of Ophthalmology,Shiyan Taihe Hospital

Publications of Results:

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Responsible Party: Bin Li, professor, Huazhong University of Science and Technology
ClinicalTrials.gov Identifier: NCT03153293     History of Changes
Other Study ID Numbers: Leber 2
First Posted: May 15, 2017    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:
LHON,G11778A mutation, rAAV2-ND4,gene therapy
Additional relevant MeSH terms:
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Optic Nerve Diseases
Optic Neuritis
Optic Atrophy, Hereditary, Leber
Nervous System Diseases
Cranial Nerve Diseases
Eye Diseases
Optic Atrophies, Hereditary
Optic Atrophy
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases