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

Phase I/IIa, Open-Label, Dose-Escalation Study of Safety and Tolerability of Intravitreal RST-001 in Patients With Advanced Retinitis Pigmentosa (RP)

All participants in phase 1 and phase 2a had hand motion visual acuity or worse.

If efficacy was demonstrated from phase 1, better vision subjects could be enrolled; however, efficacy was not demonstrated.

Study Overview

• Status: Completed
• Conditions: Advanced Retinitis Pigmentosa
• Intervention / Treatment: Drug: AGN-151597

Detailed Description

Study RST-001-CP-0001 was an open-label, dose-escalation study to evaluate the safety and tolerability of AGN-151597 (formerly RST-001) administered as a single intravitreal injection in participants with advanced RP. Three groups of approximately 3 participants each were sequentially enrolled in the dose-escalation phase (Phase 1) of this study: Group A (low dose), Group B (mid dose), and Group C (high dose).

For each dose group, the safety and tolerability of AGN-151597 was assessed by a data safety monitoring committee (DSMC) in the first participant before the remaining participants were enrolled into the group. If the DSMC considered the safety and tolerability of all participants in the dose group to be satisfactory and enrollment stopping rules had not been met, then enrollment into the next dose group could begin.

If the DSMC considered the safety and tolerability satisfactory and the enrollment stopping rules had not been met after a minimum assessment of 1 month (to include the Month 1 Visit) from treatment of the final participant in Groups A, B, or C, then the sponsor could elect to start enrollment of up to approximately 12 participants in Phase 2a to receive AGN-151597 at the maximum tolerated dose. After completion of the 2-year core study visits, each participant could enroll in a long-term follow-up for an additional 3 years to monitor the long-term safety of AGN-151597.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco - Mission Bay /ID# 235717
  • Kentucky
    • Edgewood, Kentucky, United States, 41017-3415
      • Cincinnati Eye Institute- Edgewood /ID# 236713
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Eye Center /ID# 235715
  • Texas
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest /ID# 235199

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet all of the following criteria.

1. Age >= 18 years.
2. Signed and dated written informed consent obtained from the patient.
3. Ability to comply with testing and all protocol tests.

Exclusion Criteria:

Any one of the following will exclude patients from being enrolled into the study:

1. Unable or unwilling to meet requirements of the study.
2. Participation in a clinical study (ocular or non-ocular) with an investigational drug, agent or therapy in the past six months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Low Dose; Single intravitreal injection of AGN-151597	Drug: AGN-151597; AGN-151597 is a gene therapeutic delivered by intravitreal injection
Experimental: Phase 1: Mid Dose; Single intravitreal injection of AGN-151597	Drug: AGN-151597; AGN-151597 is a gene therapeutic delivered by intravitreal injection
Experimental: Phase 1: High Dose; Single intravitreal injection of AGN-151597	Drug: AGN-151597; AGN-151597 is a gene therapeutic delivered by intravitreal injection
Experimental: Phase 2: High Dose; Single intravitreal injection of AGN-151597	Drug: AGN-151597; AGN-151597 is a gene therapeutic delivered by intravitreal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Grade 3 or Greater Adverse Event (AE) Considered Related to AGN-151597	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.	Baseline (Day 1) to 6 Months
Visual Acuity in the Study Eye at Baseline and Month 6	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.	Baseline (Day 1), 6 Months
Change From Baseline at Month 6 in Full Field Sensitivity in the Study Eye - Blue Light Threshold	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.	Baseline (Day 1) to Month 6
Change From Baseline at Month 6 in Full Field Sensitivity in the Study Eye - Red Light Threshold	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.	Baseline (Day 1) to Month 6
Change From Baseline at Month 6 in Full Field Sensitivity in the Study Eye - White Light Threshold	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.	Baseline (Day 1) to Month 6
Change From Baseline at Month 6 in Ambulation in the Study Eye (Time)	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).	Baseline (Day 1) to Month 6
Change From Baseline at Month 6 in Ambulation in the Study Eye (Distance)	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).	Baseline (Day 1) to Month 6
Intraocular Pressure (IOP) Measurements in the Study Eye	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.	Baseline (Day 1), 6 Months
Anatomical Parameters as Measured in the Study Eye by Color Fundus Photography and Autofluorescence	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.	Baseline (Day 1), 6 Months
Change From Baseline at Month 6 in the Anatomical Parameters in the Study Eye as Measured by Spectral Domain-Optical Coherence Tomography (SD-OCT) - Total Retinal Nerve Fibre Layer Volume	Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.	Baseline (Day 1) to Month 6
Change From Baseline at Month 6 in the Anatomical Parameters in the Study Eye as Measured by Spectral Domain-Optical Coherence Tomography (SD-OCT) - Total Ganglion Cell and Inner Plexiform Layer Volume	Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.	Baseline (Day 1) to Month 6
Change From Baseline at Month 6 in the Anatomical Parameters in the Study Eye as Measured by Spectral Domain-Optical Coherence Tomography (SD-OCT) - Total Retinal Volume	Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.	Baseline (Day 1) to Month 6
Change From Baseline at Month 6 in the Anatomical Parameters in the Study Eye as Measured by Spectral Domain-Optical Coherence Tomography (SD-OCT) - Total Retinal Thickness	Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.	Baseline (Day 1) to Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Acuity in the Study Eye at Months 3, 12, and 24	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.	3, 12, and 24 Months
Change From Baseline at Months 3, 12, and 24 in Full Field Sensitivity in the Study Eye - Blue Light Threshold	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.	Baseline (Day 1) to Months 3, 12, and 24
Change From Baseline at Months 3, 12, and 24 in Full Field Sensitivity in the Study Eye - Red Light Threshold	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.	Baseline (Day 1) to Months 3, 12, and 24
Change From Baseline at Months 3, 12, and 24 in Full Field Sensitivity in the Study Eye - White Light Threshold	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.	Baseline (Day 1) to Months 3, 12, and 24
Change From Baseline at Months 3, 12, and 24 in Ambulation Light-Guided Walking Test in the Study Eye (Time)	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).	Baseline (Day 1) to Months 3, 12, and 24
Change From Baseline at Months 3, 12, and 24 in Ambulation Light-Guided Walking Test in the Study Eye (Distance)	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).	Baseline (Day 1) to Months 3, 12, and 24
Change From Baseline at Months 3, 6, and 24 in Object Detection and Discrimination Scores	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.	Baseline (Day 1) to Months 3, 6, and 24
Change From Baseline at Months 3, 6, and 24 in Visual Evoked Potential (VEP) Scores in the Study Eye (SE/0.974 Amplitude)	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.	Baseline (Day 1) to Months 3, 6, and 24
Change From Baseline at Months 3, 6, and 24 in Visual Evoked Potential (VEP) Scores in the Study Eye (SE/0.649 Amplitude)	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.	Baseline (Day 1) to Months 3, 6, and 24
Change From Baseline at Months 3, 6, and 24 in Visual Evoked Potential (VEP) Scores in the Study Eye (SE/0.216 Amplitude)	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.	Baseline (Day 1) to Months 3, 6, and 24
Change From Baseline at Months 3, 6, and 24 in Visual Evoked Potential (VEP) Scores in the Study Eye (SE/0.974 Latency)	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.	Baseline (Day 1) to Months 3, 6, and 24
Change From Baseline at Months 3, 6, and 24 in Visual Evoked Potential (VEP) Scores in the Study Eye (SE/0.649 Latency)	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.	Baseline (Day 1) to Months 3, 6, and 24
Change From Baseline at Months 3, 6, and 24 in Visual Evoked Potential (VEP) Scores in the Study Eye (SE/0.216 Latency)	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.	Baseline (Day 1) to Months 3, 6, and 24
Change From Baseline at Months 6 and 24 in Electroretinogram (ERG) Scores in the Study Eye (Amplitude)	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.	Baseline (Day 1) to Months 6 and 24
Change From Baseline at Months 6 and 24 in Electroretinogram (ERG) Scores in the Study Eye (Latency)	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.	Baseline (Day 1) to Months 6 and 24
Change From Baseline at Months 3, 6, and 24 in Composite Score of National Eye Institute (NEI) Visual Functioning Questionnaire (VFQ-25) Scores	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.	Baseline (Day 1) to Months 3, 6, and 24
Anatomical Parameters as Measured in the Study Eye by Color Fundus Photography and Autofluorescence	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.	Months 3 and 24
Change From Baseline at Months 3, 12, and 24 in the Anatomical Parameters in the Study Eye as Measured by Spectral Domain-OCT (SD-OCT) - Volume	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).	Baseline to Months 3, 12, and 24
Change From Baseline at Months 3, 12, and 24 in the Anatomical Parameters in the Study Eye as Measured by Spectral Domain-OCT (SD-OCT) - Total Retinal Thickness	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).	Baseline to Months 3, 12, and 24

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

General Publications

• Simunovic MP, Shen W, Lin JY, Protti DA, Lisowski L, Gillies MC. Optogenetic approaches to vision restoration. Exp Eye Res. 2019 Jan;178:15-26. doi: 10.1016/j.exer.2018.09.003. Epub 2018 Sep 13.

Helpful Links

• Additional information on study locations near you may be found at AllerganClinicalTrials.com. For any study not on AllerganClinicalTrials.com, please contact IR-CTRegistration@Allergan.com for assistance.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2015
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): October 21, 2024

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimated): September 22, 2015

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Retina; Gene therapy; Retinitis pigmentosa; Optogenetics; Channelrhodopsin
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Retinal Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinitis Pigmentosa
• Other Study ID Numbers: RST-001-CP-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No