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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
Sponsor:
Information provided by (Responsible Party):
Bin Li, Huazhong University of Science and Technology

Tracking Information
First Submitted Date  ICMJE January 7, 2018
First Posted Date  ICMJE February 9, 2018
Last Update Posted Date July 29, 2020
Actual Study Start Date  ICMJE January 8, 2018
Actual Primary Completion Date December 6, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2018)
BCVA [ Time Frame: Change from Baseline at 12 months ]
The Best Corrected Visual Acuity
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2018)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months
Official Title  ICMJE Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
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
Condition  ICMJE
  • 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
Intervention  ICMJE Drug: rAAV2-ND4
rAAV2-ND4 of vitreous cavity injection
Other Name: rAAV2-ND4 gene therapy
Study Arms  ICMJE 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.
Intervention: Drug: rAAV2-ND4
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 26, 2019)
120
Original Estimated Enrollment  ICMJE
 (submitted: February 3, 2018)
50
Estimated Study Completion Date  ICMJE December 30, 2020
Actual Primary Completion Date December 6, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03428178
Other Study ID Numbers  ICMJE LHON(Acute)
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bin Li, Huazhong University of Science and Technology
Study Sponsor  ICMJE Bin Li
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Huazhong University of Science and Technology
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP