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Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON) (rAAV2-ND4)

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: NCT01267422
Recruitment Status : Completed
First Posted : December 28, 2010
Results First Posted : May 2, 2016
Last Update Posted : January 31, 2018
Sponsor:
Collaborator:
Huazhong University of Science and Technology
Information provided by (Responsible Party):
Bin Li, Huazhong University of Science and Technology

Tracking Information
First Submitted Date  ICMJE December 27, 2010
First Posted Date  ICMJE December 28, 2010
Results First Submitted Date  ICMJE May 21, 2015
Results First Posted Date  ICMJE May 2, 2016
Last Update Posted Date January 31, 2018
Study Start Date  ICMJE April 2011
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2016)
  • The Best Corrected Visual Acuity(BCVA) [ Time Frame: Up to 3 years ]
  • Results of CD3/CD4/CD8 Test [ Time Frame: up to 6 months ]
    The mean percentage of CD3+/CD4+/CD8+ test before and after treatment
Original Primary Outcome Measures  ICMJE
 (submitted: December 27, 2010)
The visual acuity [ Time Frame: 6 month ]
Vision testing before and after treatment
Change History Complete list of historical versions of study NCT01267422 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2016)
  • Intraocular Pressure; [ Time Frame: Up to 3 years ]
  • Neutralizing Antibody Assay [ Time Frame: up to 3 years ]
    The mean of Neutralizing antibody assay of 8 patients before and after treatment
  • Average RNFL Thickness Througth Optical Coherence Tomography(OCT) Test [ Time Frame: Up to 3 years ]
    Average RNFL thickness of 8 patients througth Optical coherence tomography(OCT) test before and after treatment
  • Computerized Visual Field(MD: Mean Deviation, the Value Close to 0 Regarded Normal) [ Time Frame: up to 3 years ]
    MD: mean deviation, the value Close to 0 regarded normal.VFI/MD:The bigger one was more close to the normal value.
  • Computerized Visual Field(VFI: Visual Field Index ,the Value Close to 100% Regarded Normal) [ Time Frame: up to 3 years ]
    VFI: visual field index ,the value Close to 100% regarded normal. VFI/MD:The bigger one was more close to the normal value.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 27, 2010)
  • Intraocular pressure [ Time Frame: 6 month ]
    Intraocular pressure testing before and after treatment
  • VEP [ Time Frame: 6 month ]
    VEP testing before and after treatment
  • computerized visual field [ Time Frame: 6 month ]
    computerized visual field testing before and after treatment
  • OCT [ Time Frame: 6 month ]
    OCT testing before and after treatment
  • ERG [ Time Frame: 6 month ]
    ERG testing before and after treatment
  • Liver and kidney function in plasma [ Time Frame: 6 month ]
    Liver and kidney function in plasma testing before and after treatment
  • ELISA [ Time Frame: 6 month ]
    Antibodies against AAV2 capsid was analyzed by ELISA using serum samples collected before injection and different time points after the injection.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON)
Official Title  ICMJE Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy
Brief Summary This study is meant to assess the safety and efficacy of rAAV2-ND4 treatment of Leber hereditary optic neuropathy with 11778 LHON mutation.
Detailed Description

Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited ocular disorder associated with a mutation in mtDNA . The common manifestation is visual loss which caused by the respiratory chain enzymes complex dysfunction resulting in increased oxidative stress enzymes production.

Material and Method Seven patients with 11778 LHON mutation were randomly treated with a Single IVT Injection of recombinant Adeno-Associated Virus-NADH dehydrogenase, subunit 4 (complex I)(rAAV2-ND4)(0.05ml).The dose was 5 × 10^9 vg/0.05 mL for patients younger than 12 years old, and 1 × 10^10 vg/0.05 mL for patients older than 12 years old. The visual acuity, visual evoked potential (VEP),optical coherence tomography( OCT), computerized visual field, electroretinograms(ERG), retinal nerve fiber layer(RNFL)and Liver and kidney function in plasma were compared before and after treatment at 1,3,and 6, months interval.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leber Hereditary Optic Neuropathy
Intervention  ICMJE Drug: rAAV2-ND4
injection
Other Name: rAAV2-ND4 gene therapy
Study Arms  ICMJE Experimental: rAAV2-ND4
injection
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 Completed
Actual Enrollment  ICMJE
 (submitted: March 29, 2016)
9
Original Estimated Enrollment  ICMJE
 (submitted: December 27, 2010)
6
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. comply with Leber hereditary optic neuropathy diagnostic criteria.
  2. in patients with informed consent, voluntary participation.
  3. signed informed consent.
  4. 8 ≤ Age ≤ 60 years old, good health, the patient can tolerate local anesthesia surgery.
  5. to comply with doctor's instructions, can in the time of referral.

Exclusion Criteria:

  1. Cardiopulmonary and renal function in severe weakness, cancer, a variety of bleeding disorders, acute sensing disease, high fever, high fever disease, women during pregnancy, heart disease, such as post-operative recovery period.
  2. Are participating in other clinical studies of patients.
  3. Patients with mental disorders.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
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 NCT01267422
Other Study ID Numbers  ICMJE RAVCT-2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
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 Huazhong University of Science and Technology
Investigators  ICMJE
Study Chair: bin Li, PhD,MD Deputy Director of Ophthalmology
PRS Account Huazhong University of Science and Technology
Verification Date January 2018

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