Neovascular Age-related Macular Degeneration
Conditions
Brief summary
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).
Detailed description
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.
Interventions
BIOLOGICALASKG712
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.
Sponsors
Visara, Inc.
Suzhou Aosaikang Biopharmaceutical Co., Ltd.
AskGene Pharma, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of ocular adverse events (AEs) of the study eyes | 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) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration time curve (AUC) | Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks | To evaluate the systemic pharmacokinetics of ASKG712 in subjects with neovascular age-related macular degeneration (nAMD) |
| Maximum plasma concentration (Cmax) | Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks | To evaluate the systemic pharmacokinetics of ASKG712 in subjects with neovascular age-related macular degeneration (nAMD) |
| Anti-Drug Antibody | Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks | To evaluate the immunogenicity of ASKG712 in subjects with neovascular age-related macular degeneration (nAMD) |
| 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 | To evaluate the efficacy of ASKG712 in subjects with neovascular age-related macular degeneration (nAMD) |
| 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 | To evaluate the efficacy of ASKG712 in subjects with neovascular age-related macular degeneration (nAMD) |
| Mean change from baseline in choroidal neovascularization area measured by fundus angiography | Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks | To evaluate the efficacy of ASKG712 in subjects with neovascular age-related macular degeneration (nAMD) |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORKun Liu, MD
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed