A Phase I/IIa Study of RS1 Ocular Gene Transfer for X-linked Retinoschisis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS
研究概览
简要总结
Background:
- X-linked juvenile retinoschisis (XLRS) is caused by changes in the RS1 gene. These changes cause abnormal function of the eye protein retinoschisin. Without normal retinoschisin, the layers of the retina split and vision is lost. Researchers want to try to introduce a healthy RS1 gene into eye cells, to see if this helps retinal cells make healthy retinoschisin. They will put the gene in a virus. The gene and virus package is known as a gene transfer vector (AAV-RS1 vector).
Objectives:
- To see if the AAV-RS1 vector is safe to use in patients with X-linked retinoschisis.
Eligibility:
- Adults 18 and older with a mutation of the RS1 gene, 20/63 vision or worse in one eye, and XLRS.
Design:
- Participants will be screened with genetic tests to confirm XLRS. They will have a medical history and physical and eye exams.
- At visits 1-2, participants will have some or all of the following:
- Medical history
- Physical exam
- Blood and urine tests
- Tuberculosis skin test
- Eye exam
- Vision tests (for one test an intravenous line will be placed in the arm. A dye will be injected that will travel to the blood vessels in the eye).
- At visit 3, the AAV-RS1 vector will be injected with a needle in the study eye. Participants pupils will be dilated. They will get numbing eye drops.
- Visits 4-13 will occur in the 18 months after gene transfer. Many of the above tests will be repeated. Participants will discuss any side effects.
- Visits 14-17 will occur yearly between years 2 and 5.
- After year 5, participants will be contacted yearly by phone for up to 15 years.
详细描述
Objective
To evaluate the safety and tolerability of ocular AAV-RS1 vector (AAV8-scRS/IRBPhRS) gene transfer to the retina of participants affected with X-linked juvenile retinoschisis (XLRS).
Study Population: Male participants affected with XLRS will receive ocular gene transfer. A maximum of up to 24 participants may be enrolled.
Design: This is a Phase I/IIa, prospective, dose escalation, single-center study. One eye of each participant will receive the AAV-RS1 gene vector application by intravitreal injection. Participants will be closely monitored in conjunction with DSMC oversight. Participants will be followed for 18 months after which they will continue to be followed for up to 5 years after enrollment, or per FDA requirements, for further safety analysis.
Outcome Measures: The primary outcome is the safety of ocular AAV-RS1 vector as determined from assessment of retinal function, ocular structure and occurrence of adverse events and laboratory tests. Secondary outcomes include changes in visual function, electroretinogram (ERG) responses, visual field measurements, retinal imaging with optical coherence tomography (OCT), and the formation of anti-AAV and anti-RS1 antibodies.
Statistics: No formal sample size calculations are used in this Phase I/IIa dose-escalation study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 4
1e11 vg/eye
干预措施: RS1 AAV Vector (Biological)
Cohort 5
3e11 vg/eye
干预措施: RS1 AAV Vector (Biological)
Cohort 1
1e9 vg/eye
干预措施: RS1 AAV Vector (Biological)
Cohort 2
1e10 vg/eye
干预措施: RS1 AAV Vector (Biological)
Cohort 3
1e11 vg/eye
干预措施: RS1 AAV Vector (Biological)
Cohort 6
Not to exceed 6e11 vg/eye
干预措施: RS1 AAV Vector (Biological)
结局指标
主要结局
Adverse Events (AEs) Affecting Ocular Function That Differ Clinically From Those Expected in the Normal Course of Progression of XLRS
时间窗: Day 0 through Year 2, inclusive
Includes a) substantial functional change (change \>=10 electronic visual acuity letters in best-corrected visual acuity from average of baseline visits), b) decrease in electroretinogram response amplitude (\>=75% from average of baseline visits), c) severe ocular inflammation beyond inflammation anticipated consequent to an intravitreal injection; d) adverse events deemed clinically-related to the intraocular administration technique, and e) abnormal laboratory findings beyond Grade 1 Common Terminology Criteria for Adverse Events v5.0 and/or clinically significantly different than baseline. a)-d) only includes events occurring in the study eye.
次要结局
- Change in Electroretinography Combined Response Amplitudes(Baseline 1 through Year 2)
- Mean Change in Best Corrected Visual Acuity(Baseline 1 through Year 2)
- Median and Distribution of Change in Best-Corrected Visual Acuity(Baseline 1 through Year 2)
- Formation of Circulating Systemic Anti-AAV or Anti-RS1 Antibodies(Day 0 through end of study participation (Year 5 or Year 7))
- Change in Retinal Structure as Measured by Optical Coherence Tomography(Baseline 1 through end of study participation (Year 5 or Year 7))
- Change in Central Visual Field Sensitivity as Measured by Microperimetry (MP-1) Visual Field Testing(Baseline 1 through end of study participation (Year 5 or Year 7))