A Prospective, Multi-Center, Open-label, Sequential, Multiple Ascending-Dose and High Concentration Cohorts Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AM712 Following Intravitreal Administration in Patients with Neovascular Age-related Macular Degeneration.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 7
- 主要终点
- Incidence of non-ocular AEs
研究概览
简要总结
The purpose of this Phase 1 study is comprised of multiple ascending-dose component (Part 1) and high concentration component (Part 2) to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in patients with neovascular age- related macular degeneration (nAMD).
详细描述
The Part 1 of study is a multicenter, open-label, sequentially, multiple ascending-dose study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in subjects with nAMD.
Subjects will be sequentially enrolled into different dose-level cohorts following the traditional "3+3" design until the maximally tolerated dose (MTD) or the maximally administered dose (MAD) has been reached.
The Part 2 of study is a multicenter, open-label, sequential study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in treatment-naïve patients with nAMD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
The Phase 1 study is comprised of open-label multiple ascending-dose component (Part 1) and high concentration component (Part 2) to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in patients with neovascular age- related macular degeneration (nAMD).
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 subjects with 50 years of age or older
- •Active sub-foveal CNV lesion secondary to nAMD including juxta or extra-foveal lesions that partially affect the fovea
- •The area of CNV must occupy at least 50% of total lesion
- •Total lesion area ≤ 12 DA
- •ETDRS BCVA letter score measured at screening and baseline
- •Clear ocular media and adequate pupil dilation to permit good quality photographic imaging in study eye
排除标准
- •Any previous systemic anti-VEGF treatment
- •Any systemic treatment or therapy to treat neovascular AMD
- •Continuous use of systemic corticosteroids
- •Diseases that affect intravenous injection and venous blood sampling
- •Presence of CNV due to other causes, such as ocular histoplasmosis, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture, or pathologic myopia in study eye
- •History or any concurrent ocular condition which, in opinion of investigator, could either confound interpretation of efficacy and safety of IP or require medical or surgical intervention.
- •The area of fibrosis occupies ≥ 50% of total lesion area in study eye
- •Evidence of myopia degeneration, diagnosis supported by the axial length examination in study eye
- •History or any concurrent macular abnormality other than AMD in study eye
- •Current vitreous hemorrhage or history of vitreous hemorrhage in study eye
- •History of recurrent inflammation in study eye
- •History of treatment for nAMD
- •Subject having out of range laboratory values defined as:
- •ALT or AST > 2 x ULN, total bilirubin > 1.5 x ULN Serum creatinine > 1.5 x ULN, BUN > 2 x ULN HbA1c > 7.5% at screening
研究组 & 干预措施
Phase I- All
Subjects with neovascular AMD
干预措施: AM712(ASKG712) (Biological)
结局指标
主要结局
Incidence of non-ocular AEs
时间窗: 252 days
To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD)
Any relevant safety observations derived from BCVA
时间窗: 252 days
To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD)
Incidence of ocular adverse events (AEs) of the study eyes
时间窗: 252 days
To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD)
Any relevant safety observations derived from SD-OCT
时间窗: 252 days
To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD)
次要结局
- Mean change from baseline in central subfield thickness as assessed by SD-OCT(252 days)
- Mean change from baseline in BCVA (ETDRS)(252 days)
- Proportion of patients gaining ≥ 15 letters from baseline BCVA(252 days)
- Proportion of patients with no intraretinal fluid, subretinal fluid, or pigment epithelial detachment as assessed by SD-OCT(252 days)