Phase I/IIa, Open-Label, Dose-Escalation Study of Safety and Tolerability of Intravitreal RST-001 in Patients With Advanced Retinitis Pigmentosa (RP)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 4
- 主要终点
- Number of Participants With Any Grade 3 or Greater Adverse Event (AE) Considered Related to AGN-151597
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria.
- •Age >= 18 years.
- •Signed and dated written informed consent obtained from the patient.
- •Ability to comply with testing and all protocol tests.
排除标准
- •Any one of the following will exclude patients from being enrolled into the study:
- •Unable or unwilling to meet requirements of the study.
- •Participation in a clinical study (ocular or non-ocular) with an investigational drug, agent or therapy in the past six months.
研究组 & 干预措施
Phase 1: Low Dose
Single intravitreal injection of AGN-151597
干预措施: AGN-151597 (Drug)
Phase 1: Mid Dose
Single intravitreal injection of AGN-151597
干预措施: AGN-151597 (Drug)
Phase 1: High Dose
Single intravitreal injection of AGN-151597
干预措施: AGN-151597 (Drug)
Phase 2: High Dose
Single intravitreal injection of AGN-151597
干预措施: AGN-151597 (Drug)
结局指标
主要结局
Number of Participants With Any Grade 3 or Greater Adverse Event (AE) Considered Related to AGN-151597
时间窗: Baseline (Day 1) to 6 Months
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 in the Study Eye at Baseline and Month 6
时间窗: Baseline (Day 1), 6 Months
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.
Change From Baseline at Month 6 in Full Field Sensitivity in the Study Eye - Blue Light Threshold
时间窗: Baseline (Day 1) to Month 6
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.
Change From Baseline at Month 6 in Full Field Sensitivity in the Study Eye - Red Light Threshold
时间窗: Baseline (Day 1) to Month 6
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.
Change From Baseline at Month 6 in Full Field Sensitivity in the Study Eye - White Light Threshold
时间窗: Baseline (Day 1) to Month 6
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.
Change From Baseline at Month 6 in Ambulation in the Study Eye (Time)
时间窗: Baseline (Day 1) to Month 6
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).
Change From Baseline at Month 6 in Ambulation in the Study Eye (Distance)
时间窗: Baseline (Day 1) to Month 6
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 (IOP) Measurements in the Study Eye
时间窗: Baseline (Day 1), 6 Months
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.
Anatomical Parameters as Measured in the Study Eye by Color Fundus Photography and Autofluorescence
时间窗: Baseline (Day 1), 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.
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
时间窗: Baseline (Day 1) to Month 6
Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.
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
时间窗: Baseline (Day 1) to Month 6
Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.
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
时间窗: Baseline (Day 1) to Month 6
Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.
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
时间窗: Baseline (Day 1) to Month 6
Qualitative assessment of the change in retinal cross-sectional appearance in the study eye from Baseline at month 6 as Measured by SD-OCT.
次要结局
- Visual Acuity in the Study Eye at Months 3, 12, and 24(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(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(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(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)(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)(Baseline (Day 1) to Months 3, 12, and 24)
- Change From Baseline at Months 3, 6, and 24 in Object Detection and Discrimination Scores(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)(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)(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)(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)(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)(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)(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)(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)(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(Baseline (Day 1) to Months 3, 6, and 24)
- Anatomical Parameters as Measured in the Study Eye by Color Fundus Photography and Autofluorescence(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(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(Baseline to Months 3, 12, and 24)