Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leber Hereditary Optic Neuropathy
Intervention Drug: rAAV2-ND4
Enrollment 9
Recruitment Details Patients diagnosed with LHON (with a verified point mutation at the 11778 nucleotide site)
Pre-assignment Details All patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 36 months.
Arm/Group Title Participants Receiving Treatment in Left Eye Participants Receiving Treatment in Right Eye
Hide Arm/Group Description 5 participants receiving treatment in left eye 4 participants receiving treatment in right eye
Period Title: Intravitreal rAAV2-ND4 Injection
Started 5 4
Completed 5 4
Not Completed 0 0
Period Title: Safety and Efficacy Study
Started 5 4
Completed 5 4
Not Completed 0 0
Arm/Group Title All Study Participants
Hide Arm/Group Description Age,Gender,Ethnicity,Race,Region of Enrollment
Overall Number of Baseline Participants 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 9 participants
15
(7.65 to 30.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
2
  22.2%
Male
7
  77.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
9
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
American Indian or Alaska Native
0
   0.0%
Asian
9
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
China Number Analyzed 9 participants
9
1.Primary Outcome
Title The Best Corrected Visual Acuity(BCVA)
Hide Description [Not Specified]
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The data are expressed as mean±standard error. Comparisons before and after treatment of the BCVA were analyzed using the paired t-test.A probability (P) value of less than 0.05 was considered statistically significant.Lower logMAR represents a better outcome.
Arm/Group Title BCVA of Un-treated Eyes BCVA of Treated Eyes
Hide Arm/Group Description:
BCVA of un-treated eyes in 9 patients
BCVA of trearted eyes in 9 patients
Overall Number of Participants Analyzed 9 9
Overall Number of Units Analyzed
Type of Units Analyzed: logMAR
9 9
Mean (Standard Error)
Unit of Measure: logMAR
before treament 1.40  (0.55) 1.69  (0.43)
1 months after treament 1.36  (0.58) 1.58  (0.44)
3 months after treament 1.31  (0.58) 1.38  (0.46)
6 months after treament 1.20  (0.68) 1.23  (0.60)
9 months after treament 1.23  (0.62) 1.27  (0.58)
2.Primary Outcome
Title Results of CD3/CD4/CD8 Test
Hide Description The mean percentage of CD3+/CD4+/CD8+ test before and after treatment
Time Frame up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title The Mean Percentage of CD3+/CD4+/CD8+ Before Treatment The Mean Percentage of CD3+/CD4+/CD8+ After Treatment
Hide Arm/Group Description:
The mean percentage of CD3+ before treatment;The mean percentage of CD4+ before treatment;The mean percentage of CD8+ before treatment
The mean percentage of CD3+ after treatment;The mean percentage of CD4+ after treatment;The mean percentage of CD8+ after treatment
Overall Number of Participants Analyzed 9 9
Mean (Full Range)
Unit of Measure: Percentage of total cells
Values of CD3+
51
(50 to 84)
53
(50 to 84)
Values of CD4+
26
(20 to 51)
20
(20 to 51)
Values of CD8+
20
(12 to 45)
13
(12 to 45)
3.Secondary Outcome
Title Intraocular Pressure;
Hide Description [Not Specified]
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title IOP Before Treatment IOP After Treatment
Hide Arm/Group Description:
Ophthalmologic examinations includes IOP of 9 paticipants before treatment
Ophthalmologic examinations includes IOP of 9 participants after treatment
Overall Number of Participants Analyzed 9 9
Mean (Full Range)
Unit of Measure: mmHg
14
(10 to 21)
16
(10 to 21)
4.Secondary Outcome
Title Neutralizing Antibody Assay
Hide Description The mean of Neutralizing antibody assay of 8 patients before and after treatment
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Neutralizing antibody assay of 8 patients except Patient 1 because he once accepted the other eye's treatment
Arm/Group Title The Mean of Neutralizing Antibody Assay Before Treatment The Mean of Neutralizing Antibody Assay After Treatment
Hide Arm/Group Description:
The mean of Neutralizing antibody assay before treatment of 8 patients
The mean of Neutralizing antibody assay after treatment of 8 patients
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: titer
0.9221  (0.142437) 0.8723  (0.201054)
5.Secondary Outcome
Title Average RNFL Thickness Througth Optical Coherence Tomography(OCT) Test
Hide Description Average RNFL thickness of 8 patients througth Optical coherence tomography(OCT) test before and after treatment
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
RNFL thickness of 8 patients except Patient 1 because he once accepted the other eye's treatment
Arm/Group Title Average RNFL Thickness Before Treatment Average RNFL Thickness After Treatment
Hide Arm/Group Description:
Average RNFL thickness before treatment of injected eyes;Average RNFL thickness before treatment of uninjected eyes
Average RNFL thickness after treatment of injected eyes;Average RNFL thickness after treatment of uninjected eyes
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: Micrometer
injected eye 47.3125  (7.87259) 46.7813  (7.5397)
uninjected eye 50.1875  (13.402) 47.9688  (9.7031)
6.Secondary Outcome
Title Computerized Visual Field(MD: Mean Deviation, the Value Close to 0 Regarded Normal)
Hide Description MD: mean deviation, the value Close to 0 regarded normal.VFI/MD:The bigger one was more close to the normal value.
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patient 2 refused the vision field test,there are MD outcome measure of 8 patients.
Arm/Group Title Mean MD Before Treatment Mean MD After Treatment
Hide Arm/Group Description:
Mean MD before treatment of injected eyes;Mean MD before treatment of uninjected eyes
Mean MD after treatment of injected eyes;Mean MD after treatment of uninjected eyes
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: dB
injected eye -29.377  (5.16805) -23.813  (7.27537)
uninjected eye -28.701  (3.65595) -23.427  (8.15747)
7.Secondary Outcome
Title Computerized Visual Field(VFI: Visual Field Index ,the Value Close to 100% Regarded Normal)
Hide Description VFI: visual field index ,the value Close to 100% regarded normal. VFI/MD:The bigger one was more close to the normal value.
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patient 2 refused the vision field test,there are VFI outcome measure of 8 patients.
Arm/Group Title Mean VFI Before Treatment Mean VFI After Treatment
Hide Arm/Group Description:
Mean VFI before treatment of injected eyes;Mean VFI before treatment of uninjected eyes
Mean VFI after treatment of injected eyes;Mean VFI after treatment of uninjected eyes
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: Percentage of normal
injected eye 11  (0.14513) 28  (0.23305)
uninjected eye 10.5  (0.28714) 25  (0.24804)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Short-term Affects Long-term Affects
Hide Arm/Group Description Lens may be injured during intravitreal injection, and cataract is probably complicated. Retinal detachment or endophthalmitis may be complicated due to retina injury.IOP raised.Endophthalmitis after treament. Hyper-susceptibility or immune response during surgery or after surgery. Lens may be injured after intravitreal injection, and cataract is probably complicated. Retinal detachment or endophthalmitis may be complicated due to retina injury.IOP raised.Blood and urine routine is affected.Liver and kidney function is affected.Immune response after surgery.
All-Cause Mortality
Short-term Affects Long-term Affects
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Short-term Affects Long-term Affects
Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/9 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Short-term Affects Long-term Affects
Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/9 (0.00%) 
Early termination leading to small numbers of subjects analyzed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bin Li
Organization: Department of Ophthalmology, Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology
Phone: +86-13638673626
EMail: libin-12@163.com
Other Publications:
Layout table for additonal information
Responsible Party: Bin Li, Huazhong University of Science and Technology
ClinicalTrials.gov Identifier: NCT01267422     History of Changes
Other Study ID Numbers: RAVCT-2
First Submitted: December 27, 2010
First Posted: December 28, 2010
Results First Submitted: May 21, 2015
Results First Posted: May 2, 2016
Last Update Posted: January 31, 2018