An Open Label, Dose Exploration, Safety and Tolerability Study of a Subretinal Injection of an OPGx-001 Gene Vector to Participants With LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) With OCncurrent Non-Interventional Follow-Up of Untreated Patients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 22
- 试验地点
- 3
- 主要终点
- Incidence of Dose Limiting Toxicities
研究概览
简要总结
The goals of this clinical trial are assess the natural course of LCA5-IRD over 6 months and to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-001 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. Funding Source- FDA Office of Orphan Products Development (OOPD).
详细描述
This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating untreated patients for 6 months and with three doses of OPGx-001 for the treatment of LCA5-IRD.
Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC).
Concurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures.
- •Are willing to adhere to the clinical protocol and able to perform testing procedures.
- •In part A participants must be 13 years of age or older at consent, for Part B, participants must be 4 years of age or older at consent with the ability to conduct the MLoMT.
- •Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (historic testing up to 15 years from date of consent can be considered).
- •Visual acuity: BCVA < 20/80 on the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart (modified for low vision participants) in the eye to be treated
- •Show evidence of detectable photoreceptors by Spectral Domain Optical Coherence Tomography (SD-OCT)
- •Participant is a good candidate for surgery per investigator judgement
- •Participant agrees to follow direction of investigator regarding restrictions post-surgery (Part A only).
排除标准
- •Women who are pregnant or individuals (women of childbearing potential and men) unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration (Part A only).
- •Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised.
- •History of intraocular surgery for either eye within 6 months prior to planned IP administration (Part A only).
- •Have previously received gene therapy.
- •Have used any investigational drug or device within 90 days or 5 estimated half-lives of treatment, whichever is longer or plan to participate in another study of drug or device during the study period.
- •History of disease which may preclude the participant from participation, or which may interfere with outcome measure testing or test results.
- •Incapable of performing visual function testing (e.g., FST testing) for reasons other than poor vision.
- •Any absolute contraindication to a course of oral steroids.
- •Any other condition that would not allow the potential participant to complete follow-up examinations during the study and, in the opinion of the Investigator, makes the potential participant unsuitable for the study.
研究组 & 干预措施
Dose Group 1
A single, unilateral, subretinal injection of low dose (1E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a low dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).
干预措施: AAV8.hLCA5 (Biological)
Dose Group 2
A single, unilateral, subretinal injection of an intermediate dose (3E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of an intermediate dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).
干预措施: AAV8.hLCA5 (Biological)
Dose Group 3
A single, unilateral, subretinal injection of high dose (1E11 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a high dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).
干预措施: AAV8.hLCA5 (Biological)
Part B Observational
Part B will occur concurrently with Dose Groups 1-3. Sixteen patients will be assessed for 6 months to assess the natural course of LCA5-IRD, then will be treated with OPGx-001 which will be described in a future protocol amendment.
结局指标
主要结局
Incidence of Dose Limiting Toxicities
时间窗: 2 years
Number of DLT events
Number of adverse events related to OPGx-001
时间窗: 2 years
Number of AEs related to IP
Incidence of adverse events related to OPGx-001
时间窗: 2 years
Incidence of AEs related to IP
Severity of adverse events related to OPGx-001
时间窗: 2 years
Severity of AEs related to IP
Number of procedure-related adverse events
时间窗: 2 years
Number of AEs related to IP administration
Incidence of procedure-related adverse events
时间窗: 2 years
Incidence of AEs related to IP administration
Severity of procedure-related adverse events
时间窗: 2 years
Severity of AEs related to IP administration
Assessment of cross-sectional spectral domain optical coherence tomography images
时间窗: 2 years
Qualitative Assessment of SD-OCT image
Assessment of Natural course of LCA5-IRD
时间窗: 6 months
Change from baseline in MLoMT
次要结局
- Change from baseline over time in Multi-luminance Orientation and Mobility Test(2 years)
- Change from baseline over time in Dark-adapted full-field sensitivity testing(2 years)
- Change from baseline over time in best corrected visual acuity (BCVA)(2 years)
- Change from baseline over time in visual functioning questionnaire(1 year)