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

Study Overview
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Brief Summary
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The purpose of the Phase 1 study is comprised of single ascending-dose component (Part 1) and multiple ascending-dose component (Part 2) to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ASKG712 in patients with neovascular age-related macular degeneration (nAMD).

Detailed Description
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The Part 1 of study is a multicenter, open-label, sequentially, single ascending-dose study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ASKG712 in subjects with nAMD. The Part 2 of study is a multicenter, open-label, sequentially, multiple ascending-dose (3 doses) study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ASKG712 in subjects with nAMD. 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.

Official Title
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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

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Biological: ASKG712


Participation Criteria
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Eligibility Criteria
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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 opinion of 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 30 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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASKG712<br>Single or multiple ascending dose of ASKG712 by intravitreal injection | Biological: ASKG712<br>* ASKG712 is a recombinant anti-VEGF humanized monoclonal antibody and Ang-2 antagonist peptide fusion protein, which has high specificity for the binding of VEGF-A and Ang-2.<br>* Other names: AM712;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of ocular adverse events (AEs) of the study eyes | Any relevant ocular observations assessed by best corrected visual acuity (BCVA) , slitlamp examination, ophthalmoscopy, intraocular pressure, fundus photography, optical coherence tomography (OCT) and angiography | Part 1: 6 weeks; Part 2: 20 weeks | 
| Incidence of non-ocular adverse events (AEs) | Any changes of clinical safety observations assessed by vital signs, electrocardiograph (ECG), clinical laboratory tests and physical examination | Part 1: 6 weeks; Part 2: 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration time curve (AUC) | To evaluate the systemic pharmacokinetics of ASKG712 in subjects with neovascular age-related macular degenerationn (nAMD) | Part 1: 6 weeks; Part 2: 20 weeks | 
| Maximum plasma concentration (Cmax) | To evaluate the systemic pharmacokinetics of ASKG712 in subjects with neovascular age-related macular degenerationn (nAMD) | Part 1: 6 weeks; Part 2: 20 weeks | 
| Anti-Drug Antibody | To evaluate the immunogenicity of ASKG712 in subjects with neovascular age-related macular degenerationn (nAMD) | Part 1: 6 weeks; Part 2: 20 weeks | 
| Mean change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment of Diabetic Retinopathy Study (ETDRS) letter score | To evaluate the efficacy of ASKG712 in subjects with neovascular age-related macular degenerationn (nAMD) | Part 1: 6 weeks; Part 2: 20 weeks | 
| Mean change from baseline in central subfield thickness (CST) of macula measured by optical coherence tomography (OCT) | To evaluate the efficacy of ASKG712 in subjects with neovascular age-related macular degenerationn (nAMD) | Part 1: 6 weeks; Part 2: 20 weeks | 
| Mean change from baseline in choroidal neovascularization area measured by fundus angiography | To evaluate the efficacy of ASKG712 in subjects with neovascular age-related macular degenerationn (nAMD) | Part 1: 6 weeks; Part 2: 20 weeks |