A Double-center, Open-label,Single Ascending Dose Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Intravitreous Injections of RC28-E (a Chimeric Decoy Receptor Trap Fusion Protein by Dual Blockage of VEGF and FGF-2) in Subjects With Wet Age-Related Macular Degeneration
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Neovascular Age-related Macular Degeneration
- Sponsor
- RemeGen Co., Ltd.
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Incidence of ocular and systemic adverse events and serious adverse events which are related to RC28-E
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this first-in-human study is to evaluate the safety, tolerability and pharmacokinetics of single intravitreous injections,single ascending doses, of RC28-E(a chimeric decoy receptor trap fusion protein by dual blockage of VEGF and FGF-2) in subjects with wet age-related macular degeneration (wAMD).
Detailed Description
This is an open-label, non-randomized,double-center phase 1 study evaluating pharmacokinetics, safety and tolerability of single intravitreal injections of RC28-E in the patients with AMD.RC28-E is recombinant dual decoy receptor IgG1 Fc-fusion protein,can block VEGF-A and FGF-2. In preclinical studies suggested that RC28-E might be more effective in inhibiting pathological angiogenesis than other VEGF antagonists on CNV. Every subject will only accept one dose. In addition to safety and preliminary efficacy, pharmacokinetics and immunogenicity of RC28-E will be evaluated as well.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients or their legal representative signed informed consent;
- •Aged 50 years to 80 years, male or female;
- •Best corrected VA for the studied eye≥34 letters, ≤73 letters(By ETDRS chart);
- •With choroidal neovascular (CNV) lesions secondary to neovascular AMD;
- •If both eyes meet the criteria, severe illness eye will be selected; if both eyes are the same, the right eye will be selected as the study eye.
Exclusion Criteria
- •History of any vitreous hemorrhage with 2 months prior to screening;
- •Presence of scar, fibrosis or atrophy in central foveal of the study eye;
- •Significant refractive media opacity, including cataract, may interfere with visual assessment;
- •The studied eye suffered pseudoexfoliation syndrome, central retinal vein occlusion, intraocular hemorrhage resulting in decreased vision, rhegmatogenous retinal detachment, macular hole, choroidal neovascularization (CNV) for any reason other than AMD (such as fundus angioid streaks, ocular histoplasmosis, pathologic myopia, trauma);
- •Afferent pupillary defect(APD);
- •The intraocular pressure is higher than 25mmHg despite medication treatment;
- •Active infectious conjunctivitis, keratitis, scleritis, uveitis and endophthalmitis;
- •Best corrected VA for the studied eye≤19 letters(By ETDRS chart);
- •Topical or grid photocoagulation within 3 months before screening;
- •Uncontrolled diabetes mellitus(fast glucose level≥7.0 mmol/L or ≥11.1 mmol/L 2h after meal;
Outcomes
Primary Outcomes
Incidence of ocular and systemic adverse events and serious adverse events which are related to RC28-E
Time Frame: 42 days
Secondary Outcomes
- Maximum observed maximum plasma concentration (Cmax)(42 days)
- Change in Best Corrected Visual Acuity (BCVA) from baseline(42 days)
- Time to reach the maximum observed plasma concentration (Tmax)(42 days)
- Area under the plasma concentration-time curve(AUC)(42 days)
- T1/2(Terminal phase half life after single dose)(42 days)
- Change in Central Retinal Thickness（CRT）from baseline(42 days)