A Study of ASKG712 in Patients With Diabetic Macular Edema

Study Overview
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Brief Summary
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This multicenter, non-randomized, open-label, multiple-dose-escalation and dose-expansion study will investigate the safety, tolerability, pharmacokinetics and efficacy of ASKG712 following intravitreal administration in patients with diabetic macular edema (DME).

Detailed Description
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The Part 1 of study is a multicenter, open-label, sequentially, multiple-dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and efficacy of ASKG712 in patients with DME. Patients will be sequentially enrolled into four different dose-level cohorts following accelerated titration combined with the traditional 3+3 design. The Part 2 of study is a multicenter, open-label, sequentially, dose-expansion study to evaluate the safety, tolerability, pharmacokinetics and efficacy of ASKG712 in patients with DME.

Official Title
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A Multicenter, Non-Randomized, Open-Label, Multiple-Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of ASKG712 Following Intravitreal Administration in Patients With Diabetic Macular Edema

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Biological: ASKG712


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of diabetes mellitus (Type 1 or Type 2) Hemoglobin A1c of less than or equal to 12% For women of childbearing potential: agreement to use acceptable contraceptive methods during the treatment period and for at least 90 days after the final dose of study treatment Ability and willingness to undertake all scheduled visits and assessments Macular thickening secondary to DME involving the center of the fovea Decreased visual acuity attributable primarily to DME Exclusion Criteria: History of allergy or current allergic response to ASKG712 or fluorescein Diseases that affect intravenous injection and venous blood sampling Uncontrolled blood pressure Systemic autoimmune diseases Previous anti-VEGF drug treatment Currently pregnant or breastfeeding, or intend to become pregnant during the study Any uncontrolled clinical disorders Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye History of intraocular or periocular corticosteroid treatment in the study eye Uncontrolled previous or current glaucoma in the study eye Previous intraocular operations in the study eye Active intraocular or periocular infection or active intraocular inflammation in the study eye History of uveitis in either eye Other protocol-specified inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 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>Multiple doses 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 |
| --- | --- | --- |
| 1. Incidence of ocular adverse events (AEs) of the study eyes | Any relevant ocular observations derived from best corrected visual acuity (BCVA), intraocular pressure, slitlamp examination, ophthalmoscopy, optical coherence tomography (OCT), fundus photography, and angiography | 24 weeks | 
| 2. Incidence of non-ocular AEs | Any clinical safety observations assessed by physical examination, vital signs, electrocardiograph (ECG) and clinical laboratory tests | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Area under the concentration time curve (AUC) | To evaluate the systemic pharmacokinetics of ASKG712 in patients with DME | 24 weeks | 
| 2. Maximum plasma concentration (Cmax) | To evaluate the systemic pharmacokinetics of ASKG712 in patients with DME | 24 weeks | 
| 3. Incidence of Anti-Drug Antibody (ADA) | To evaluate the immunogenicity of ASKG712 in patients with DME | 24 weeks | 
| 4. Change From Baseline in BCVA in the Study Eye Over Time | To evaluate the efficacy of ASKG712 in patients with DME | 24 weeks |