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
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- AskGene Pharma, Inc.
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Incidence of ocular adverse events (AEs) of the study eyes
Overview
Brief Summary
The purpose of the Phase 1 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
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.
The Part 3 of study is a multicenter, open-label, randomized, multiple ascending-dose (3 doses) study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ASKG712 in subjects with nAMD at 2 recommanded dose levels.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 50 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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 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 60 days prior to screening；
Arms & Interventions
ASKG712
Single or multiple ascending dose of ASKG712 by intravitreal injection
Intervention: ASKG712 (Biological)
Outcomes
Primary Outcomes
Incidence of ocular adverse events (AEs) of the study eyes
Time Frame: 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) , slitlamp examination, ophthalmoscopy, intraocular pressure, fundus photography, optical coherence tomography (OCT) and angiography
Incidence of non-ocular adverse events (AEs)
Time Frame: 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 Outcomes
- Area under the concentration time curve (AUC)(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks)
- Maximum plasma concentration (Cmax)(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks)
- Anti-Drug Antibody(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks)
- 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)
- 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)
- Mean change from baseline in choroidal neovascularization area measured by fundus angiography(Part 1: 6 weeks; Part 2: 20 weeks; Part 3: 20 weeks)