Trial Outcomes & Findings for Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis (NCT NCT00999609)
NCT ID: NCT00999609
Last Updated: 2025-04-23
Results Overview
The MLMT measures changes in functional vision, as assessed by the ability to navigate a course accurately and at a reasonable pace at different levels of environmental illumination. MLMT was assessed using both eyes at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night). Each light level was assigned a score code ranging from 0 to 6. A higher score indicated that a subject was able to pass the MLMT at a lower light level. A score of -1 was assigned to those who could not pass MLMT at 400 lux. The MLMT of each subject was videotaped and assessed by independent graders. The MLMT score was determined by the lowest light level at which the subject was able to pass the MLMT. The MLMT score change was defined as the difference between the score at Baseline and the score at Year 1. A positive MLMT score change from Baseline to Year 1 visit indicated that the subject was able to complete the MLMT at a lower light level.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE3
Target enrollment
31 participants
Primary outcome timeframe
One year (change from baseline)
Results posted on
2025-04-23
Participant Flow
Participant milestones
| Measure |
Intervention
Bilateral subretinal injection of voretigene neparvovec-rzyl (AAV2-hRPE65v2), 1.5x 10e11 vg in a total volume of 0.3ml per eye, administered no fewer than 6 days apart
|
Control
No intervention, no sham; uninjected control group
|
|---|---|---|
|
Overall Study
STARTED
|
21
|
10
|
|
Overall Study
COMPLETED
|
20
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
Baseline characteristics by cohort
| Measure |
Intervention
n=21 Participants
Bilateral subretinal injection of voretigene neparvovec-rzyl (AAV2-hRPE65v2), 1.5x 10e11 vg in a total volume of 0.3ml per eye, administered no fewer than 6 days apart
|
Control
n=10 Participants
Control group did not receive voretigene neparvovec-rzyl. The control group became eligible to receive voretigene neparvovec-rzyl 1 year after their baseline evaluations, provided they still met all eligibility criteria.
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
14.7 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
15.9 years
STANDARD_DEVIATION 9.5 • n=7 Participants
|
15.1 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
|
Age, Customized
Age Group · <10 years old
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Age, Customized
Age Group · ≥10 years old
|
12 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Multi-luminance Mobility Test (MLMT), bilateral, passing at a lux level of < 125 or ≥ 125 lux
Lowest passing light level of < 125 lux
|
12 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Multi-luminance Mobility Test (MLMT), bilateral, passing at a lux level of < 125 or ≥ 125 lux
Lowest passing light level of ≥ 125 lux
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: One year (change from baseline)The MLMT measures changes in functional vision, as assessed by the ability to navigate a course accurately and at a reasonable pace at different levels of environmental illumination. MLMT was assessed using both eyes at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night). Each light level was assigned a score code ranging from 0 to 6. A higher score indicated that a subject was able to pass the MLMT at a lower light level. A score of -1 was assigned to those who could not pass MLMT at 400 lux. The MLMT of each subject was videotaped and assessed by independent graders. The MLMT score was determined by the lowest light level at which the subject was able to pass the MLMT. The MLMT score change was defined as the difference between the score at Baseline and the score at Year 1. A positive MLMT score change from Baseline to Year 1 visit indicated that the subject was able to complete the MLMT at a lower light level.
Outcome measures
| Measure |
Intervention
n=21 Participants
Bilateral, subretinal injection of voretigene neparvovec-rzyl (AAV2-hRPE65v2)
|
Control
n=10 Participants
No intervention, no sham; uninjected control group
|
|---|---|---|
|
Multi-luminance Mobility Testing (MLMT), Bilateral
|
1.8 Score Change in Light Levels
Standard Deviation 1.1
|
0.2 Score Change in Light Levels
Standard Deviation 1.0
|
SECONDARY outcome
Timeframe: One year (change from baseline)Measures the light sensitivity of the entire visual field by recording the luminance at which a subject reliably reports seeing the dimmest flash.
Outcome measures
| Measure |
Intervention
n=21 Participants
Bilateral, subretinal injection of voretigene neparvovec-rzyl (AAV2-hRPE65v2)
|
Control
n=10 Participants
No intervention, no sham; uninjected control group
|
|---|---|---|
|
Full-field Light Sensitivity Threshold (FST) Testing: White Light
|
-2.08 log10(cd.s/(m^2))
Standard Error 0.29
|
0.04 log10(cd.s/(m^2))
Standard Error 0.44
|
SECONDARY outcome
Timeframe: One year (change from baseline)The MLMT measures changes in functional vision, as assessed by the ability to navigate a course accurately and at a reasonable pace at different levels of environmental illumination. MLMT was assessed using the first eye at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night). Each light level was assigned a score code ranging from 0 to 6. A higher score indicated that a subject was able to pass the MLMT at a lower light level. A score of -1 was assigned to those who could not pass MLMT at 400 lux. The MLMT of each subject was videotaped and assessed by independent graders. The MLMT score was determined by the lowest light level at which the subject was able to pass the MLMT. The MLMT score change was defined as the difference between the score at Baseline and the score at Year 1. A positive MLMT score change from Baseline to Year 1 visit indicated that the subject was able to complete the MLMT at a lower light level.
Outcome measures
| Measure |
Intervention
n=21 Participants
Bilateral, subretinal injection of voretigene neparvovec-rzyl (AAV2-hRPE65v2)
|
Control
n=10 Participants
No intervention, no sham; uninjected control group
|
|---|---|---|
|
Multi-luminance Mobility Testing (Monocular)
|
1.9 Score Change in Light Levels
Standard Deviation 1.2
|
0.2 Score Change in Light Levels
Standard Deviation 0.6
|
SECONDARY outcome
Timeframe: One year (change from baseline)Measurement of the sharpness of vision, determined by the ability to read letters on a standardized chart from a specified distance.
Outcome measures
| Measure |
Intervention
n=21 Participants
Bilateral, subretinal injection of voretigene neparvovec-rzyl (AAV2-hRPE65v2)
|
Control
n=10 Participants
No intervention, no sham; uninjected control group
|
|---|---|---|
|
Visual Acuity
|
-0.16 LogMAR
Standard Error 0.07
|
0.01 LogMAR
Standard Error 0.10
|
Adverse Events
Intervention
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
Control
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Intervention
n=20 participants at risk
Bilateral subretinal injection of voretigene neparvovec-rzyl (AAV2-hRPE65v2), 1.5x 10e11 vg in a total volume of 0.3ml per eye, administered no fewer than 6 days apart
|
Control
n=9 participants at risk
No intervention, no sham; uninjected control group
|
|---|---|---|
|
Surgical and medical procedures
Adverse Drug Reaction
|
10.0%
2/20 • Number of events 2 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Nervous system disorders
Convulsion
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
Other adverse events
| Measure |
Intervention
n=20 participants at risk
Bilateral subretinal injection of voretigene neparvovec-rzyl (AAV2-hRPE65v2), 1.5x 10e11 vg in a total volume of 0.3ml per eye, administered no fewer than 6 days apart
|
Control
n=9 participants at risk
No intervention, no sham; uninjected control group
|
|---|---|---|
|
Eye disorders
Cataract
|
15.0%
3/20 • Number of events 4 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Elevated intraocular pressure
|
20.0%
4/20 • Number of events 5 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Retinal tear
|
10.0%
2/20 • Number of events 2 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Eye inflammation
|
10.0%
2/20 • Number of events 6 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Conjunctival cyst
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Conjunctivis viral
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Eye irritation
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Eye pain
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Eye pruritus
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Eye swelling
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Foreign body sensation in eyes
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Iritis
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Macular hole/degeneration
|
5.0%
1/20 • Number of events 2 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Maculopathy/ epiretinal membrane
|
5.0%
1/20 • Number of events 2 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Pseudopapilledema
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Retinal hemorrhage
|
5.0%
1/20 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
0.00%
0/9 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
|
Eye disorders
Photopsia
|
0.00%
0/20 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
11.1%
1/9 • Number of events 1 • 1 year post administration (Intervention group), 1 year post baseline (Control group)
The safety population (n=29) includes all subjects who received injection in either eye for the intervention group and all control group subjects who did not withdraw, or were not withdrawn, prior to any of the following people knowing the treatment assignment: the subject, parent, Principal Investigator, or Medical Monitor.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place