Ranibizumab in Patients With Choroidal Neovascularization Secondary to Causes Other Than Age-Related Macular Degeneration: A Phase I Study

Abstract

Purpose:: Vascular endothelial growth factor A (VEGF-A) has been implicated in the development of choroidal neovascularization (CNV) and in the increased vascular permeability of CNV, which can lead to central vision loss. Because the most common cause of CNV is age-related macular degeneration (AMD), most FDA-approved treatments are for CNV secondary to AMD, and there is an unmet clinical need for treatment for patients with CNV secondary to other causes. One recently FDA-approved treatment of CNV secondary to AMD is ranibizumab (Lucentis^TM), a humanized antigen-binding antibody fragment that inhibits all active isoforms and cleavage products of VEGF-A and has been shown to stabilize and improve vision in patients with neovascular AMD. This study evaluates the safety and efficacy of ranibizumab in patients with CNV secondary to causes other than AMD.

Methods:: In this ongoing, single-center, open-label, 12-month trial, patients with CNV secondary to causes other than AMD are randomized to receive 3 monthly intravitreal injections of either 0.3 mg or 0.5 mg ranibizumab, with the potential for additional injections at the physician’s discretion. The primary objective is to assess the safety and tolerability of ranibizumab in this patient population, and the secondary objective is to assess the efficacy of ranibizumab by ETDRS visual acuity (VA) testing, fluorescein angiography, and optical coherence tomography (OCT).

Results:: To date, 6 enrolled patients with myopic macular degeneration (4), angioid streaks (1), and idiopathic CNV (1) have received a mean of 3.7 injections of ranibizumab (range, 2-5) with a mean of 4.8 months (range, 1-7) of follow-up. Four patients received 0.3-mg ranibizumab injections, and 2 received 0.5-mg ranibizumab injections. No serious local or systemic adverse events have been observed. At 6 months of follow-up (n = 4), the mean change in VA was +6.3 letters, and the mean reduction in central retinal thickness as measured by OCT was 56.3 µm.

Conclusions:: Based on preliminary data, this is the first report that ranibizumab appears to be well-tolerated and effective in patients with CNV secondary to causes other than AMD.

Clinical Trial:: www.clinicaltrials.gov NCT00395551

Keywords: choroid: neovascularization • growth factors/growth factor receptors