A Study of ASKG712 in Patients With Neovascular Age-Related Macular Degeneration

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

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).

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.