AGN-151597 (Formerly RST-001) Phase I/II Trial for Advanced Retinitis Pigmentosa

An adverse event is any untoward medical occurrence in a subject or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Visual acuity of the study eye (with fellow eye covered) was measured using low vision assessment of count fingers, hand motion, and light perception.

For count fingers testing, the examiner's hand presenting 1, 2, or 5 fingers is held 2 feet in front of the eye being examined. If the participant correctly identifies three of five presentations, then count fingers vision is noted. If not, then the participant must be tested for hand motion vision.

For hand motion testing, the examiner's hand is extended 2 feet in front of the eye and moved horizontally or vertically. If the participant correctly identifies hand movement four out of five times, then hand motion vision is noted. If not, then the participant is tested for light perception.

For light perception testing, a beam of light is directed in and out of the eye at least four times from a distance of 3 feet. If the participant correctly perceives the light, vision should be recorded as yes to light perception.

The light sensitivity of the visual field was measured by recording the threshold at which a participant reported seeing the dimmest flash. A negative value indicates an increase in sensitivity from baseline.

The light sensitivity of the visual field was measured by recording the threshold at which a participant reported seeing the dimmest flash. A negative value indicates an increase in sensitivity from baseline.

The light sensitivity of the visual field was measured by recording the threshold at which a participant reported seeing the dimmest flash. A negative value indicates an increase in sensitivity from baseline.

Evaluated a participant's ability to navigate within a dark room. The time from the start to stop and the distance from the center of the lit panel to where the participant stopped or touched the target (panel) were recorded. The test was first performed binocularly, then on the study eye (with non-study eye patched). A negative value indicates a decrease from baseline in time or distance from start to stop (improvement).

Evaluated a participant's ability to navigate within a dark room. The time from the start to stop and the distance from the center of the lit panel to where the participant stopped or touched the target (panel) were recorded. The test was first performed binocularly, then on the study eye (with non-study eye patched). A negative value indicates a decrease from baseline in time or distance from start to stop (improvement).

Intraocular pressure was measured using the Goldmann applanation tonometer or a hand-held tonometer (same instrument used for each participant throughout the study, when possible). Measurements were taken at baseline (pre-injection) and at 6 months.

A standardized procedure for the collection of single, non-stereo images of the fundus of both eyes was obtained using the same equipment for each participant throughout the study.

Evidence of increased inflammation, hemorrhage, retinal detachment, RPE disturbance or atrophy in the fovea, and any changes from baseline visit were documented. Any changes from baseline in fundus autofluorescence were also documented.

Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.

Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.

Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.

Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.

Visual acuity of the study eye (with fellow eye covered) was measured using low vision assessment of count fingers, hand motion, and light perception.

For count fingers testing, the examiner's hand presenting 1, 2, or 5 fingers is held 2 feet in front of the eye being examined. If the participant correctly identifies three of five presentations, then count fingers vision is noted. If not, then the participant must be tested for hand motion vision.

For hand motion testing, the examiner's hand is extended 2 feet in front of the eye and moved horizontally or vertically. If the participant correctly identifies hand movement four out of five times, then hand motion vision is noted. If not, then the participant is tested for light perception.

For light perception testing, a beam of light is directed in and out of the eye at least four times from a distance of 3 feet. If the participant correctly perceives the light, vision should be recorded as yes to light perception.

The light sensitivity of the visual field was measured by recording the threshold at which a participant reported seeing the dimmest flash. A negative value indicates an increase in sensitivity from baseline.

The light sensitivity of the visual field was measured by recording the threshold at which a participant reported seeing the dimmest flash. A negative value indicates an increase in sensitivity from baseline.

The light sensitivity of the visual field was measured by recording the threshold at which a participant reported seeing the dimmest flash. A negative value indicates an increase in sensitivity from baseline.

Evaluated a participant's ability to navigate within a dark room. The time from the start to stop and the distance from the center of the lit panel to where the participant stopped or touched the target (panel) were recorded. The test was first performed binocularly, then on the study eye (with non-study eye patched). A negative value indicates a decrease from baseline in time or distance from start to stop (improvement).

Evaluated a participant's ability to navigate within a dark room. The time from the start to stop and the distance from the center of the lit panel to where the participant stopped or touched the target (panel) were recorded. The test was first performed binocularly, then on the study eye (with non-study eye patched). A negative value indicates a decrease from baseline in time or distance from start to stop (improvement).

Participants were to perform two tests concurrently, first identifying if a light displayed on an LED screen can be seen and then if a series of standard images (square, circle, triangle, or star) presented on the screen can be identified. The shapes were presented in blue or red at varying intensities. Data on light color and threshold intensity of the light was collected; shape detection data was not collected. The change from baseline in threshold intensity at 3, 6, and 24 months is reported. A negative change from baseline suggests an improvement.

Visual Evoked Potential (VEP) is an eye assessment that measures how the brain responds to visual stimuli. The pattern of visual evoked potentials was obtained from each eye using a VEP stimulator according to standard protocols. Three different visual stimuli were assessed. Amplitude measures how strong the signal is when your brain responds to visual stimuli. A higher amplitude indicates an improvement and a lower amplitude indicates a worsening outcome. Latency is the time it takes for the signal to reach the brain after the visual stimulus is presented. A shorter latency indicates an improvement from baseline; a longer latency indicates a worsening outcome.

Visual Evoked Potential (VEP) is an eye assessment that measures how the brain responds to visual stimuli. The pattern of visual evoked potentials was obtained from each eye using a VEP stimulator according to standard protocols. Three different visual stimuli were assessed. Amplitude measures how strong the signal is when your brain responds to visual stimuli. A higher amplitude indicates an improvement and a lower amplitude indicates a worsening outcome. Latency is the time it takes for the signal to reach the brain after the visual stimulus is presented. A shorter latency indicates an improvement from baseline; a longer latency indicates a worsening outcome.

Visual Evoked Potential (VEP) is an eye assessment that measures how the brain responds to visual stimuli. The pattern of visual evoked potentials was obtained from each eye using a VEP stimulator according to standard protocols. Three different visual stimuli were assessed. Amplitude measures how strong the signal is when your brain responds to visual stimuli. A higher amplitude indicates an improvement and a lower amplitude indicates a worsening outcome. Latency is the time it takes for the signal to reach the brain after the visual stimulus is presented. A shorter latency indicates an improvement from baseline; a longer latency indicates a worsening outcome.

Visual Evoked Potential (VEP) is an eye assessment that measures how the brain responds to visual stimuli. The pattern of visual evoked potentials was obtained from each eye using a VEP stimulator according to standard protocols. Three different visual stimuli were assessed. Amplitude measures how strong the signal is when your brain responds to visual stimuli. A higher amplitude indicates an improvement and a lower amplitude indicates a worsening outcome. Latency is the time it takes for the signal to reach the brain after the visual stimulus is presented. A shorter latency indicates an improvement from baseline; a longer latency indicates a worsening outcome.

Visual Evoked Potential (VEP) is an eye assessment that measures how the brain responds to visual stimuli. The pattern of visual evoked potentials was obtained from each eye using a VEP stimulator according to standard protocols. Three different visual stimuli were assessed. Amplitude measures how strong the signal is when your brain responds to visual stimuli. A higher amplitude indicates an improvement and a lower amplitude indicates a worsening outcome. Latency is the time it takes for the signal to reach the brain after the visual stimulus is presented. A shorter latency indicates an improvement from baseline; a longer latency indicates a worsening outcome.

Visual Evoked Potential (VEP) is an eye assessment that measures how the brain responds to visual stimuli. The pattern of visual evoked potentials was obtained from each eye using a VEP stimulator according to standard protocols. Three different visual stimuli were assessed. Amplitude measures how strong the signal is when your brain responds to visual stimuli. A higher amplitude indicates an improvement and a lower amplitude indicates a worsening outcome. Latency is the time it takes for the signal to reach the brain after the visual stimulus is presented. A shorter latency indicates an improvement from baseline; a longer latency indicates a worsening outcome.

Full field electroretinography based on standards set by the ERG Standardization Committee of the International Society for Clinical Electrophysiology of Vision (ISCEV) was performed at the Screening visit, 6 months, and at 24 months. ERG tests how well the light sensitive part of the eye (retina) is working. Several assessments were performed to evaluate how well different parts of the retina respond to light in different settings. Amplitude is the strength of the electrical signal that the retina produces in response to light during an ERG test. Higher amplitude in A-wave or b-wave indicates improvement; lower amplitude indicates worsening.

Full field electroretinography based on standards set by the ERG Standardization Committee of the International Society for Clinical Electrophysiology of Vision (ISCEV) was performed at the Screening visit, 6 months, and at 24 months. ERG tests how well the light sensitive part of the eye (retina) is working. Several assessments were performed to evaluate how well different parts of the retina respond to light in different settings. Amplitude is the strength of the electrical signal that the retina produces in response to light during an ERG test. Latency is the time it takes for the retina to respond after a light is flashed in the eye during an ERG test. Shorter latency indicates an improvement; longer latency indicates a worsening.

Change in quality of life, based on composite scores of the NEI VFQ-25 from Baseline at 3, 6, and 24 months. The NEI VFQ-25 consists of 25 vision-targeted questions that represent 11 vision-related quality of life subscales and one general health item. The 11 subscales are general vision, difficulty with near vision activities, difficulty with distance vision activities, limitation in social functioning due to vision, role limitation due to vision, dependency on others due to vision, mental health symptoms due to vision, driving difficulties, limitation with peripheral vision, limitation with color vision, and ocular pain. NEI VFQ-25 scores range from 0 to 100, with a higher score representing better functioning. A positive value change from baseline indicates an improvement in vision-related quality of life.

A standardized procedure was used for the collection of single, non-stereo images of the fundus of both eyes using the same equipment for each participant throughout the study.

Evidence of increased inflammation, hemorrhage, retinal detachment, RPE disturbance or atrophy in the fovea, and any changes from baseline visit were documented. Presence or absence of changes from baseline in fundus autofluorescence were also documented.

Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at Months 3, 12, and 24 as Measured by Spectral Domain-OCT (SD-OCT).

Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at Months 3, 12, and 24 as Measured by Spectral Domain-OCT (SD-OCT).