Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration. A Phase I/II Multicenter, Controlled, Multidose Study

Abstract

Objective: To assess safety of repeated intravitreal injections of ranibizumab in treating neovascular age-related macular degeneration (AMD), and to assess changes in visual acuity (VA) and AMD lesion characteristics. Design: Multicenter, controlled, open-label, clinical trial. Participants: Sixty-four patients with subfoveal predominantly or minimally classic AMD-related choroidal neovascularization. Methods: In part 1, subjects were randomized to monthly intravitreal ranibizumab for 3 months (4 injections of 0.3 mg or 1 injection of 0.3 mg followed by 3 injections of 0.5 mg; n = 53) or usual care (UC; n = 11). In part 2, subjects could continue their regimen for 3 additional months or cross over to the alternative treatment. Main Outcome Measures: Adverse events (AEs), intraocular pressure (IOP), VA, and lesion characteristics assessed by fluorescein angiography and fundus photography. Results: Of the 64 randomized subjects, 62 completed the 6-month study. Twenty of 25 subjects (80%) randomized to 0.3 mg, and 22 of 28 subjects (79%) randomized to 0.5-mg ranibizumab in part 1 continued on that treatment in part 2; 9 of 11 (82%) subjects randomized to UC in part 1 crossed over to ranibizumab treatment in part 2. The most common AEs with ranibizumab were reversible inflammation and minor injection-site hemorrhages. Serious AEs were iridocyclitis, endophthalmitis, and central retinal vein occlusion (1 subject each). Postinjection, IOP increased transiently in 22.6% of ranibizumab-treated eyes in parts 1 and 2. After 4 ranibizumab injections (day 98), mean (± standard deviation) VA had increased 9.4±13.3 and 9.1±17.2 letters in the 0.3- and 0.5-mg groups, respectively, but had decreased 5.1±9.6 letters with UC. In part 2 (day 210), VA increased from baseline 12.8±14.7 and 15.0±14.2 letters in subjects continuing on 0.3 and 0.5 mg, respectively. Visual acuity improved from baseline ≥15 letters in 26% (day 98) and 45% (day 210) of subjects initially randomized to and continuing on ranibizumab, respectively, and areas of leakage and subretinal fluid decreased. No UC subject had a ≥15-letter improvement at day 98. Conclusions: Repeated intravitreal injections of ranibizumab had a good safety profile and were associated with improved VA and decreased leakage from choroidal neovascularization in subjects with neovascular AMD. © 2006 American Academy of Ophthalmology.