Results of a Phase I, Dose–Escalation, Safety, Tolerability, and Bioactivity Study of Intravitreous VEGF Trap in Patients With Neovascular Age–Related Macular Degeneration

Abstract

Purpose: : To determine the safety, tolerability, maximum tolerated dose, and bioactivity of intravitreous injection of VEGF Trap in patients with neovascular age–related macular degeneration (AMD).

Methods: : Patients with neovascular AMD who had lesions < 12 disc areas in size with at least 50% active choroidal neovascularization and best–corrected visual acuity (VA) of ≤ 20/40 (ETDRS protocol) received a single intravitreous injection of VEGF Trap at day 0. Safety assessments included eye examinations, vital signs, and laboratory tests (hematology, chemistry, urinalysis, levels of VEGF Trap and antibodies directed against VEGF Trap). Measures of bioactivity were changes from baseline in VA, excess foveal thickness and excess macular volume determined by optical coherence tomography, and lesion size and leakage determined by fluorescein angiography. Patients were monitored for 12 weeks following VEGF Trap administration.

Results: : Three patients at each of 4 dose levels, 0.05, 0.15, 0.5, and 1 mg, have been enrolled. There have been no serious adverse events and no identifiable intraocular inflammation. Excess foveal thickness and excess macular volume decreased rapidly after injection of VEGF Trap. At day 29, excess foveal thickness was reduced by at least 70% in 75% of patients and VA was stable or improved in 75% of patients.

Conclusions: : Intravitreous injection of up to 1 mg of VEGF Trap has been well–tolerated. Although the number of patients in each cohort is small, preliminary evidence of bioactivity in patients with neovascular AMD has been seen. Higher doses are being investigated to identify the ideal dose of VEGF Trap for a phase II trial in patients with neovascular AMD.

Keywords: macula/fovea • choroid: neovascularization • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials