A Phase I/IIa (Phase 1/Phase 2a), Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of Gene Therapy With RGX-314 in Subjects With Neovascular AMD (nAMD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 16
- 主要终点
- Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))
研究概览
简要总结
Excessive vascular endothelial growth factor (VEGF) plays a key part in promoting neovascularization and edema in neovascular (wet) age-related macular degeneration (nAMD). VEGF inhibitors (anti-VEGF), including ranibizumab (LUCENTIS®, Genentech) and aflibercept (EYLEA®, Regeneron), have been shown to be safe and effective for treating nAMD and have demonstrated improvement in vision. However, anti-VEGF therapy is administered frequently via intravitreal injection and can be a significant burden to the patients. RGX-314 is a recombinant adeno-associated virus (AAV) gene therapy vector carrying a coding sequence for a soluble anti-VEGF protein. The long-term, stable delivery of this therapeutic protein following a 1 time gene therapy treatment for nAMD could potentially reduce the treatment burden of currently available therapies while maintaining vision with a favorable benefit:risk profile.
详细描述
This Phase I/IIa, open-label, multiple-cohort, dose-escalation study was designed to evaluate the safety and tolerability of RGX-314 gene therapy in subjects with previously treated nAMD. Five doses were studied in approximately 42 subjects. Subjects who met the inclusion/exclusion criteria and had an anatomic response to an initial anti-VEGF injection received a single dose of RGX-314 administered by subretinal delivery. RGX-314 uses an AAV8 vector that contains a gene that encodes for a monoclonal antibody fragment which binds to and neutralizes VEGF activity. Safety was the primary focus for the initial 24 weeks after RGX-314 administration (primary study period). Following completion of the primary study period, subjects continued to be assessed until 104 weeks following treatment with RGX-314.
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
- 50 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 50 and ≤ 89 years with a diagnosis of subfoveal CNV (Choroidal neovascularization) secondary to AMD in the study eye receiving prior intravitreal anti-VEGF therapy.
- •BCVA (Best Corrected Visual Acuity) between ≤20/63 and ≥20/400 (≤63 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/40 and ≥20/400 (≤73 and ≥19 ETDRS letters) for the rest of the cohort.
- •History of need for and response to anti-VEGF therapy.
- •Response to anti-VEGF at trial entry (assessed by SD-OCT (Spectral Domain Optical Coherence Tomography) at week 1)
- •Must be pseudophakic (status post cataract surgery) in the study eye.
- •AST (Aspartate aminotransferase)/ALT (Alanine aminotransferase) < 2.5 × ULN (Upper limit of normal); TB (Total bilirubin) < 1.5 × ULN; PT (Prothrombin time) < 1.5 × ULN; Hb > 10 g/dL (males) and > 9 g/dL (females); Platelets > 100 × 10^3/µL; eGFR (Estimated glomerular filtration rate) > 30 mL/min/1.73 m^2
- •Must be willing and able to provide written, signed informed consent.
排除标准
- •CNV or macular edema in the study eye secondary to any causes other than AMD.
- •Any condition preventing visual acuity improvement in the study eye, eg, fibrosis, atrophy, or retinal epithelial tear in the center of the fovea.
- •Active or history of retinal detachment in the study eye.
- •Advanced glaucoma in the study eye.
- •History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening.
- •Presence of an implant in the study eye at screening (excluding intraocular lens).
- •Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within the past 6 months.
- •Uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100 mmHg) despite maximal medical treatment.
结局指标
主要结局
Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events))
时间窗: 26 weeks (24 weeks following RGX-314 administration)
Participants with ocular and non-ocular AEs and SAEs through 26 weeks (24 weeks following RGX-314 administration)
次要结局
- Change From Baseline in BCVA (Best Corrected Visual Acuity)(106 weeks (104 weeks following RGX-314 administration))
- Change From Baseline in CRT (Central Retinal Thickness)(106 weeks (104 weeks following RGX-314 administration))
- Supplemental Injections (Annualized Rate of Supplemental Injections)(106 weeks (104 weeks following RGX-314 administration))
- Mean Change From Baseline in Area of CNV (Choroidal Neovascularization)(106 weeks (104 weeks following RGX-314 administration))
- Safety (Participants With Ocular and Non-ocular AEs and SAEs)(106 weeks (104 weeks following RGX-314 administration))