Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Incidence of adverse events (AEs) |
Incidence of adverse events (AEs) within 52 weeks of NR082 intravitreal injection at different doses |
52 weeks |
|
Primary |
Incidence of serious adverse events (SAEs) |
Incidence of serious adverse events (SAEs)within 52 weeks of NR082 intravitreal injection at different doses |
52 weeks |
|
Primary |
Incidence of dose-limiting toxicities (DLT) |
Incidence of dose-limiting toxicities (DLT) (ocular and non-ocular) within 52 weeks of NR082 intravitreal injection at different doses |
52 weeks |
|
Secondary |
Proportion (percent) of subjects with an improvement of = 0.3 LogMAR from baseline in Best corrected visual acuity(BCVA) in the study eye |
ETDRS visual acuity charts will used to assess proportion (percent) of subjects with an improvement of = 0.3 LogMAR from baseline in Best corrected visual acuity(BCVA) |
At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260 |
|
Secondary |
Mean change from baseline in BCVA (LogMAR) in the study eye |
ETDRS visual acuity charts will used to assess mean change from baseline in BCVA (LogMAR) |
At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260 |
|
Secondary |
Mean change in BCVA (LogMAR) compared to nadir* |
ETDRS visual acuity charts will used to assess mean change in BCVA (LogMAR) compared to nadir |
At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260 |
|
Secondary |
Change from baseline in thepattern standard deviation (PSD)in the study eye |
Visual field parameters will evaluate alterations in function of different region the retina. The HVF analyzer is used to perform standard automated perimetry, and the kinetic visual field is measured by the Humphrey static visual field automatically detected by the computer, including the foveal and macular thresholds, as well as the central field. Change from baseline in thepattern standard deviation (PSD)in the study eye. |
At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260 |
|
Secondary |
Change from baseline in the visual field index (VFI) in the study eye |
Visual field parameters will evaluate alterations in function of different region the retina. The HVF analyzer is used to perform standard automated perimetry, and the kinetic visual field is measured by the Humphrey static visual field automatically detected by the computer, including the foveal and macular thresholds, as well as the central field. Change from baseline in the visual field index (VFI) in the study eye. |
At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260 |
|
Secondary |
Change from baseline in the mean deviation (MD) in the study eye |
Visual field parameters will evaluate alterations in function of different region the retina. The HVF analyzer is used to perform standard automated perimetry, and the kinetic visual field is measured by the Humphrey static visual field automatically detected by the computer, including the foveal and macular thresholds, as well as the central field. Change from baseline in the mean deviation (MD) in the study eye. |
At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260 |
|
Secondary |
Change from baseline in spatial frequency parameters of contrast sensitivity in the study eye |
The contrast sensitivity examination measures the subject's ability to discern targets presented at varying spatial frequencies or sizes under different contrast levels. The contrast sensitivity examination measures the full range of visual sensitivity, including brightness and contrast, and it may be used as a comprehensive assessment of visual function |
At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260 |
|
Secondary |
Change from baseline in visual evoked potential (VEP) parameters in the study eye |
VEP is a visual electrophysiological examination used to identify possible ischemic optic neuropathy,including the P100 Latency,P100 Amplitude,P2 Latency,P2 Amplitude. |
At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260 |
|
Secondary |
To evaluate immunogenicity |
A central laboratory will be used to evaluate anti-AAV2 neutralizing antibodies in the serum samples of all subjects.These samples will be tested by the sponsor or its designee to detect anti-AAV2 neutralizing antibodies in the samples and report the titer of confirmed positive samples. Samples confirmed positive for anti-AAV2 neutralizing antibodies will also be evaluated for the presence of neutralizing antibodies. |
At Weeks 1, 2, and 6 |
|
Secondary |
To evaluate immunogenicity |
The interferon gamma enzyme-linked immunospot (ELISpot) assay will be performed to measure the proliferative response of lymphocytes to AAV2 antigen and ND4 peptide.The number of activated cells in the sample was calculated. |
At Weeks 1, 2, 6, 12, 26, 40, and 52 |
|
Secondary |
To evaluate vector shedding |
Assessment of vector DNA shedding in tears (both eyes).Samples were analyzed to determine the presence of viral DNA in tears . |
At Weeks 1, 2, 6, 12, 26, 40, and 52 |
|
Secondary |
To evaluate biodistribution |
Assessment of biodistribution in whole blood.Samples were analyzed to determine the presence of viral DNA in whole blood. |
At Weeks 1, 2, 6, 12, 26, 40, and 52 |
|
Secondary |
To evaluate the improvement in BCVA of the study eye (< 0.3 LogMAR) |
ETDRS visual acuity charts will used to assess proportion (percent) of subjects with an improvement of = 0.2 LogMAR and = 0.1 LogMAR from baseline in BCVA Proportion (percent) of subjects with visual acuity of > 1.0 LogMAR before and after treatment |
At Weeks 52, 78, 104, 156, 208, and 260 |
|
Secondary |
To evaluate the change from baseline in VFQ-25 |
VFQ-25 is a 25-item short form version of the 51-item National Eye Institute Visual Function Questionnaire (NEI VFQ), which can effectively measure patient-reported outcomes (including quality of life, QoL).It consists of 25 items from 12 dimensions. The total score and the score of each dimension are the mean values of non-missing items of corresponding dimensions or items, with the score range from 0 to 100 , higher scores mean a worse outcome. |
At Weeks 2, 26, 52, 104, 156, 208, and 260 |
|
Secondary |
To evaluate the change from baseline in quality of SF-36 |
The SF-36 questionnaire is a universal tool for evaluating patient-reported QoL outcome. SF-36 comprises 36 questions which cover eight domains of health: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The scale score of each domain will be calculated based on the total score of the items included in the said domain and re-adjusted to 0-100,higher scores mean a worse outcome. |
At Weeks 2, 26, 52, 104, 156, 208, and 260 |
|
Secondary |
Change from baseline in retinal nerve fiber layer (RNFL) thickness of the study eye |
OCT is an imaging technology to investigate the ocular fundus by using of the basic principle of low-coherence light interferometry. It detects the reflection or diffusion signals of biological tissue layers of different depths by inputting low-coherence light and obtains the images and quantitative results of the microscopic structure of the retina |
At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260 |
|
Secondary |
Change from baseline in retinal ganglion cell complex thickness of the study eye |
OCT is an imaging technology to investigate the ocular fundus by using of the basic principle of low-coherence light interferometry. It detects the reflection or diffusion signals of biological tissue layers of different depths by inputting low-coherence light and obtains the images and quantitative results of the microscopic structure of the retina |
At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260 |
|
Secondary |
To evaluate the visual function improvement after NR082 treatment |
Early Treatment Diabetic Retinopathy Study(ETDRS) visual acuity charts will used to assess proportion (percent) of subjects with an improvement of = 0.3 LogMAR from baseline in Best corrected visual acuity(BCVA) of the non-study eye |
At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260 |
|