Abstract
Purpose: :
To assess safety of E10030, an intravitreal anti-PDGF aptamer targeting pericytes, in combination with ranibizumab in subjects with NV-AMD.
Methods: :
Dose-escalating, uncontrolled, single- and multiple-dose, multicenter phase 1 study. Included were subjects with predominantly or minimally classic subfoveal NV-AMD ≤ 5 disc areas in total lesion size. Subjects were enrolled in a dose escalation scheme to a single injection of 0.03 mg/eye and 3 monthly injections of ranibizumab 0.5 mg/eye (n=3), or to three monthly injections of one of 4 different doses of E10030 (0.03, 0.3, 1.5, 3.0 mg/eye) and ranibizumab (0.5mg/eye) (n=3-8/dose). Assessments included vital signs and clinical lab tests, complete ocular examination with intraocular pressure, standardized ETDRS visual acuity, color fundus photos and fluorescein angiography, and optical coherence tomography.
Results: :
No evidence of drug related adverse events were detected. All of the ocular adverse events were associated with the intravitreal injection. In the combined analysis of all subjects to date, 7/22 (32%), 9/20 (45%) and 9/15 (60%) subjects gained ≥ 15 letters at weeks 4, 8, and 12 respectively. The mean change in visual acuity was +11.1, +13.4 and + 15.7 ETDRS letters at weeks 4 (n=22), 8 (n=20), and 12 (n=15). The mean center point retinal thickness was 395µm at baseline, 251µm at week 4, 231µm at week 8, and 229µm at week 12. 85% of lesions exhibited neovascular regression to date as assessed by fluorescein angiography.
Conclusions: :
E10030 combined with ranibizumab in patients with subfoveal NV-AMD was well tolerated in this Phase 1 study. Although limited by the small sample size, short follow-up, and lack of a control group, results suggest potential bioactivity associated with regression of the neovascular membrane.
Clinical Trial: :
www.clinicaltrials.gov NCT00569140
Keywords: age-related macular degeneration • vascular endothelial growth factor • choroid: neovascularization