Abstract
Purpose: :
To determine the safety, tolerability, and bioactivity of intravitreal injection of KH902 in patients with neovascular age-related macular degeneration (AMD). KH902 is a fully human, fusion protein of key domains from VEGF receptor, including the Ig-like domain 4 of VEGFR2, with human IgG Fc.
Methods: :
Patients over 50 years of age with choroidal neovascularization (CNV) due to neovascular AMD with lesion size ≤12 disc areas and best-corrected ETDRS protocol visual acuity (VA) of ≤20/100 were administered a single intravitreal injection of KH902 at 1 of 6 escalating doses (0.05, 0.15, 0.5, 1.0, 2.0 or 3.0 mg per eye) at day 0 with escalation to the next dose level occurring only after the safety and tolerability was established through post-injection day 14 for the previous dose level. Follow-up examinations were performed on postinjection days 1, 3, 7, 14 and 42.
Results: :
Twenty-five patients were enrolled across 5 dose levels (0.05 mg to 2.0 mg). The results of the first 19 patients are presented. There were no serious or drug-related systemic adverse events; ocular adverse events were mild to moderate in severity. The most common ocular adverse events were transient IOP elevation after KH902 injections and injections-site subconjunctival hemorrhage, There were no reports of significant ocular inflammation or endophathalmitis. The mean VA, foveal thickness (FT), and total macular volume (TMV) were 17.58±16.90 letters,377.58±128.05 microns, and 8.23±1.83 cubic microns, respectively. At Day 42 post-injection, the mean change in VA was +20 letters and no subject lost ≥ 1 letter, and VA improved ≥ 15 letters from baseline in 12 out of 19 subjects. Anatomically, the mean change in foveal thickness was -104 microns and total macular volume was -1.05 cubic microns. The mean decrease in CNV area was 33.3%.
Conclusions: :
Intravitreal injection of up to 1.0 mg of KH902 has been well-tolerated. Although the number of patients in each cohort is small, KH902 appears to produce rapid clinical effects on VA, supported by improvements in anatomical features, in patients with neovascular AMD.
Keywords: age-related macular degeneration • choroid: neovascularization • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials