A phase I study of intravitreal vascular endothelial growth factor trap-eye in patients with neovascular age-related macular degeneration.

PURPOSE: To determine the safety, tolerability, maximum tolerated dose, and bioactivity of an intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye, a fusion protein of binding domains from human VEGF receptors 1 and 2 with human immunoglobulin-G Fc that binds VEGF family members, in patients with neovascular age-related macular degeneration (AMD). DESIGN: Dose-escalation, multicenter, interventional clinical trial. PARTICIPANTS: Twenty-one patients (13 female, 8 male) with neovascular AMD (NVAMD) and lesions or=50% active choroidal neovascularization (CNV) with best-corrected visual acuity (BCVA) or=3 lines and 3 patients requiring no adjunctive treatment of any type for 12 weeks. Some showed elimination of fluorescein leakage and reduction in area of CNV. CONCLUSIONS: Intravitreal injection of up to 4 mg of VEGF Trap-Eye in patients with NVAMD was well tolerated with no evidence of ocular inflammation. Although the number of patients in each cohort was small, there was evidence of bioactivity, because several patients, especially those receiving 2 or 4 mg of VEGF Trap-Eye, showed substantial improvement in BCVA associated with reductions in foveal thickness. Phase III trials to investigate the efficacy of intraocular VEGF Trap-Eye in patients with NVAMD are under way.