Results of a Phase I, Safety, Tolerability, and Bioactivity Study of Intravitreal VEGF Trap in Patients With Neovascular Age-Related Macular Degeneration: The CLEAR-IT 1 Study

Abstract

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

Methods:: In part A of the study, 21 patients who had neovascular AMD with lesions ≤ 12 disc areas and best-corrected visual acuity (VA) of ≤ 20/40 (ETDRS protocol) were administered a single intravitreal injection of VEGF Trap at day 0. Subsequently, in Part C, patients were randomly assigned to receive a single injection of 0.15 or 4 mg VEGF Trap. Safety assessments included eye examinations, vital signs, and laboratory tests. Measures of bioactivity included changes from baseline in VA, foveal thickness, determined by optical coherence tomography, as well as total lesion and CNV area determined by fluorescein angiography. Patients could receive injections of other anti-VEGF agents beginning 6 weeks post-injection in part A. Beginning 8 weeks post-injection, part C patients could receive follow-up injections of VEGF Trap based on criteria similar to those specified in the PRONTO study.

Results:: No serious adverse events and no identifiable intraocular inflammation have been reported. In part A, the mean decrease in excess foveal thickness for all patients was 126µ at 6 weeks, and the mean increase in BCVA was 4.75 letters; the mean decrease in CNV area was 34.5%. In the two highest dose groups (2 and 4 mg), the mean increase in BCVA was 13.5 letters, with 3 of 6 patients demonstrating improvement of ≥ 3 lines. Fifteen of 21 part-A patients received follow-up injections in the study eye after week 6; mean time to re-treatment for these patients, who received only a single intravitreal injection of VEGF Trap, was over 150 days (range 45-420 days).

Conclusions:: Intravitreal injection of up to 4 mg of VEGF Trap has been well-tolerated; no evidence of ocular inflammation has been detected. Although the number of patients in each cohort is small, VEGF Trap appears to produce rapid and durable clinical effects on BCVA, supported by improvements in anatomical features, in patients with neovascular AMD.

Clinical Trial:: www.clinicaltrials.gov NCT00320775

Keywords: age-related macular degeneration • choroid: neovascularization • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials