A Multi-Center, Randomized, Double-Masked Phase 2 Study to Assess Safety and Efficacy of ADVM-022 (AAV.7m8-aflibercept) in Anti-VEGF Treatment-Experienced Patients With Neovascular (Wet) Age-related Macular Degeneration (nAMD) [LUNA]
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 69
- 试验地点
- 78
- 主要终点
- Severity of ocular and non-ocular adverse events
研究概览
简要总结
Neovascular or wet age-related macular degeneration (nAMD) is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent intravitreal (IVT) injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product being developed for the treatment of nAMD and offers the potential for sustained intraocular expression of aflibercept following a single IVT injection. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF therapy in clinical practice.
详细描述
This Phase 2, multi-center, randomized, double-masked, parallel group study is designed to evaluate the safety, tolerability, and efficacy of a single IVT injection of ADVM-022 at one of two doses (2 × 10^11 vg/eye [2E11] or 6 × 10^10 vg/eye [6E10]) accompanied by one of four prophylactic corticosteroid treatment regimens.
Anti-VEGF treatment-experienced study participants meeting the eligibility criteria that will be randomized between the 2E11 vg/eye and 6E10 vg/eye ADVM-022 doses each with 4 prophylaxis arms for a total of 8 treatment arms, and only one eye per study participant will be selected as the study eye.
Safety, tolerability, and efficacy will be evaluated for a period of approximately 5 years from baseline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants, ≥ 50 years of age
- •Willing and able to provide written, signed informed consent for this study
- •Demonstrated a meaningful response to anti-VEGF therapy
- •Participants must be under active anti-VEGF treatment for wet AMD and received a minimum of 2 injections within 4 months prior to screening for the treatment of choroidal neovascularization secondary to nAMD in the study eye
- •Vision of the study eye at Baseline: BCVA in the range of 25 - 83 ETDRS letters, inclusive (approximate Snellen equivalent visual acuity range of 20/25 - 20/320)
- •Vision of the non-study eye at Baseline: BCVA ≥ 35 ETDRS letters (approximate Snellen equivalent of 20/200 or better)
排除标准
- •Any condition that could affect the interpretation of results or render the participant at high risk of treatment complications in the opinion of the Investigator
- •Ocular or periocular infection or intraocular inflammation in either eye within 1 month prior to or at the Randomization Visit (Day -7)
- •Uncontrolled diabetes or HbA1c ≥ 7.0 %
- •History or evidence of significant uncontrolled concomitant disease within 6 months of the Screening visit
- •Any history of ongoing bleeding disorders or INR >3.0
- •History or evidence of macular or retinal disease other than nAMD
- •History or evidence of retinal detachment or retinal pigment epithelium rip/tear
- •Uncontrolled ocular hypertension or glaucoma
- •Prior treatment with photodynamic therapy or retinal laser for the treatment of nAMD
- •Any history of vitrectomy or any other vitreoretinal surgery
- •Prior treatment with gene therapy at any time or any non-gene therapy investigational treatment or medical device in the study eye within 3 months of the Screening Visit or 5 half-lives of the investigational medicinal product
结局指标
主要结局
Severity of ocular and non-ocular adverse events
时间窗: Up to Week 52
Severity of ocular and non-ocular adverse events
Incidence of ocular and non-ocular adverse events
时间窗: Up to Week 52
Incidence of ocular and non-ocular adverse events
Mean change in best corrected visual acuity (BCVA) from Baseline
时间窗: Baseline up to Week 52
BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
次要结局
- Incidence of ocular and non-ocular adverse events(Up to 60 months)
- Percentage of participants without CST fluctuations(Baseline up to 5 years)
- Percentage of participants without post-prophylactic inflammation(Baseline up to 5 years)
- Severity of ocular and non-ocular adverse events(Up to 60 months)
- Percentage of participants from Baseline who lose/gain at least 5, 10 or 15 letters in BCVA(Baseline up to 5 years)
- Mean change in BCVA from Baseline(Baseline up to 5 years)
- Percentage of participants who are supplemental aflibercept injection-free(Baseline up to 5 years)
- Mean change in Central Subfield Thickness (CST) from Baseline(Baseline up to 5 years)
- Mean number of CST fluctuations from Baseline(Baseline up to 5 years)
- Percent reduction in annualized anti-VEGF injections(Baseline up to 5 years)