A Multi-Center, Open-label, Single Ascending-Dose and Multiple Ascending-Dose Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ASKG712 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
- Visara, Inc.
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Incidence of ocular adverse events (AEs) of the study eyes
研究概览
简要总结
The purpose of the Phase 1/2a study is comprised of single ascending-dose component (Part 1), multiple ascending-dose component (Part 2) and multiple-dose extension component (Part 3) to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ASKG712 in patients with neovascular age-related macular degeneration (nAMD).
详细描述
Part 1 of the study is a multicenter, open-label, sequential, single ascending-dose study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ASKG712 in subjects with nAMD.
Part 2 of the study is a multicenter, open-label, sequential, multiple ascending-dose (3 loading doses) study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ASKG712 in subjects with nAMD.
Part 3 of the study is a Phase 2a, multicenter, open-label, randomized, multiple ascending-dose (3 loading doses) expansion study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of the 3.0 mg and 6.0 mg doses of ASKG712 in subjects with nAMD.
For Parts 1 and 2, subjects will be sequentially enrolled into different dose-level cohorts following the "3+3" design to determine the maximum tolerated dose (MTD) or the maximum administered dose has been reached. For Part 3 subjects will be randomized 2:1 to the 6.0mg and 3.0mg dose arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Signed the informed consent form;
- •2. Male or female subjects with 50~80 years of age;
- •3. Active sub-foveal or juxta-foveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD);
- •4. Total lesion area ≤ 12 disc area (DA);
- •5. BCVA letter score measured at screening of 19~78 letters.
排除标准
- •1. History of uveitis in either eye；
- •2. Current active inflammation or infection in the study eye;
- •3. Central foveal scar, fibrosis or atrophy of macular in the study eye;
- •4. Subretinal hemorrhage area in the study eye ≥ 50% of total lesion size;
- •5. Scar or fibrosis area in study eyes ≥ 50% of total lesion size;
- •6. History or any concurrent ocular condition which, in the opinion of the investigator, could either confound interpretation of efficacy and safety of ASKG712 or require medical or surgical intervention.
- •7. Presence of retinal pigment epithelial tear;
- •8. Previous intraocular operations in the study eye;
- •9. Uncontrolled previous or current glaucoma in either eye, or previous glaucoma filtering operation in the study eye;
- •10. Previous anti-VEGF drug treatment within 60 days prior to screening；
- •11. Diseases that affect intravenous injection and venous blood sampling;
- •12. Systemic autoimmune diseases;
- •13. Any uncontrolled clinical disorders;
- •14. History of allergy or current allergic response to ASKG712 or fluorescein;
- •15. Pregnant or nursing women;
- •16. Subjects should be excluded in the opinion of investigators.
研究组 & 干预措施
ASKG712
Single or multiple ascending dose of ASKG712 by intravitreal injection
干预措施: ASKG712 (Biological)
结局指标
主要结局
Incidence of ocular adverse events (AEs) of the study eyes
时间窗: Part 1: 6 weeks; Part 2: 20 weeks; Part 3: up to 36 weeks
Any relevant ocular observations assessed by best corrected visual acuity (BCVA), slit lamp examination, ophthalmoscopy, intraocular pressure, fundus photography, optical coherence tomography (OCT) and angiography
Incidence of non-ocular adverse events (AEs)
时间窗: Part 1: 6 weeks; Part 2: 20 weeks; Part 3: up to 36 weeks
Any changes of clinical safety observations assessed by vital signs, electrocardiograph (ECG), clinical laboratory tests and physical examination
次要结局
- Mean change from baseline in choroidal neovascularization area measured by fundus angiography(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks)
- Area under the concentration time curve (AUC)(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks)
- Maximum plasma concentration (Cmax)(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks)
- Anti-Drug Antibody(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks)
- Mean change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment of Diabetic Retinopathy Study (ETDRS) letter score(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: up to 36 weeks)
- Mean change from baseline in central subfield thickness (CST) of macula measured by optical coherence tomography (OCT)(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: up to 36 weeks)