Safety and Efficacy of AM712 in Patients With nAMD

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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.

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Biological: AM712(ASKG712)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 50 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: Phase I- All<br>Subjects with neovascular AMD | Biological: AM712(ASKG712)<br>* AM712 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>|

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 | To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD) | 252 days | 
| Incidence of non-ocular AEs | To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD) | 252 days | 
| Any relevant safety observations derived from BCVA | To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD) | 252 days | 
| Any relevant safety observations derived from SD-OCT | To evaluate the safety and tolerability of AM712 in Subjects with neovascular Age-related Macular Degeneration (nAMD) | 252 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in central subfield thickness as assessed by SD-OCT | To evaluate the efficacy of AM712 in Subjects with nAMD | 252 days | 
| Proportion of patients with no intraretinal fluid, subretinal fluid, or pigment epithelial detachment as assessed by SD-OCT | To evaluate the efficacy of AM712 in Subjects with nAMD | 252 days | 
| Mean change from baseline in BCVA (ETDRS) | To evaluate the efficacy of AM712 in Subjects with nAMD | 252 days | 
| Proportion of patients gaining ≥ 15 letters from baseline BCVA | To evaluate the efficacy of AM712 in Subjects with nAMD | 252 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nAMD