A Single and Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Treatment Effect of Intravitreal AVD-104 in Participants With Geographic Atrophy Secondary to Age-related Macular Degeneration
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 107
- 主要终点
- Occurrence of Dose Limiting Toxicity in Part 1
研究概览
简要总结
Investigate the Safety, Pharmacokinetics, and Treatment effects of Single and Multi-dose of Intravitreal AVD-104 in participants with geographic atrophy secondary to age-related macular degeneration.
详细描述
Part 1 of the trial will be a multi-center, open label safety and dose escalation study with a potential enrollment of 30 participants having geographic atrophy (GA) secondary to macular degeneration. They will receive a single intravitreal injection of study drug (AVD-104) and will be followed for 3 months for safety observation. They will have both aqueous humor and peripheral blood drawn for pharmacokinetic and pharmacodynamic evaluations.
Part 2 will be a multi-center, double masked, randomized trial to evaluate the treatment effect of AVD-104 on participants with geographic atrophy secondary to macular degeneration. Participants will be randomized to high dose AVD-104, low dose AVD-104, or active comparator (avacincaptad). The primary endpoint will be the difference in the rate of growth of the GA area as measured by fundus autofluorescence.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 2 - Double Masked, Randomized, Multi-Center
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BCVA in the study eye using ETDRS Chart Visual Acuity Scale (VAS) of 5 to 55 letters (equivalent to Snellen VA of approximately 20/800 - 20/80)
- •If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA)
- •GA may be center involved.
- •BCVA in the study eye using ETDRS Chart VAS of 24 letters or better (equivalent to Snellen VA of 20/320 or better)
- •Confirmed diagnosis of AMD that is non-center involving (i.e., non-sub-foveal) GA in 50% of participants. Center involvement allowed in 50% of participants.
- •The entire GA lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Part 1 and 2
- •- Presence of the following ocular conditions - in the Study Eye:
- •Exudative AMD or choroidal neovascularization (CNV), including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere based on spectral domain optical coherence tomography (SD-OCT) imaging and/or fluorescein angiography as assessed by the Reading Center.
- •Any ocular condition other than GA secondary to AMD that may require surgery or medical intervention during the study period or, in the opinion of the Investigator, could compromise visual function during the study period.
研究组 & 干预措施
Part 2: High dose AVD-104
100 participants will be randomized and treated with bimonthly intravitreal injections of high-dose AVD-104 for the first 12 months. They will continue bimonthly injections for months 13-24.
干预措施: AVD-104 (Drug)
Part 2: Low dose AVD-104
100 participants will be randomized and treated with monthly intravitreal injections of low dose AVD-104 for 24 months.
干预措施: AVD-104 (Drug)
Part 1
Participants will receive a single intravitreal injection of AVD-104 at one of 4 escalating doses. All participants will be followed up for safety until Month 3.
干预措施: AVD-104 (Drug)
Part 2: Avacincaptad
100 participants will be randomized to receive monthly injections of avacincaptad (2 mg. intravitreal)
干预措施: Avacincaptad (Drug)
结局指标
主要结局
Occurrence of Dose Limiting Toxicity in Part 1
时间窗: 3 months
The number of participants experiencing a dose limiting toxicity corresponding to a category of 3 or greater on the National Cancer Institute Common Terminology Criteria for Adverse Events
The Rate of Change in Area of Geographic Atrophy at Month 12 in Participants in Part 2
时间窗: 12 months
The rate of change from baseline in area of GA as measured by fundus autofluorescence at month 12.
次要结局
- Prevention of Vision Loss from Baseline in Participants in Part 2(12 months)