In addition to data from the 2 phase III clinical trials, data from phase I/II studies were also included in the FDA review. In an open-label, 2-center, uncontrolled, randomized, phase I clinical trial, Rosenfeld and colleagues (2006) examined if multiple intravitreal doses of up to 2 mg of ranibizumab can be tolerated and are biologically active when injected using a dose-escalating strategy in eyes of patients with neovascular AMD. A total of 32 patients with primary or recurrent sub-foveal choroidal neovascularization secondary to AMD were enrolled. Baseline best-corrected VA in the study eye was from 20/40 to 20/640 (Snellen equivalent). Treatment regimens consisted of 5, 7, or 9 intravitreal injections of ranibizumab at 2- or 4-week intervals for 16 weeks, with escalating doses ranging from to mg. Patients were evaluated through day 140, 4 weeks after their last injection. Safety was assessed based on ocular and non-ocular adverse events, changes in VA, changes in intraocular pressure (IOP), slit-lamp ocular examination, changes in lesion characteristics based on fluorescein angiography and color fundus photography, and the presence of anti-ranibizumab antibodies. A total of 29 patients received an injection at baseline, and 27 patients completed the study through day 140. Results were similar across the 3 treatment groups. All patients experienced ocular adverse events, most of which were mild. The most common ocular adverse events were iridocyclitis (83 %), and injection-site reactions (72 %). Inflammation did not increase with repeated injections, despite the increasing ranibizumab doses. Transient mild IOP elevations were common after ranibizumab injection. No serum anti-ranibizumab antibodies were detected. In general, median and mean VAs in the study eyes improved by day 140 in all 3 groups. Only 3 of the 27 patients lost significant vision. There was no significant lesion growth, and a decrease in area of leakage from choroidal neovascularization was detected through day 140. The authors concluded that multiple intravitreal injections of ranibizumab at escalating doses ranging from to mg were well-tolerated and biologically active in eyes with neovascular AMD through 20 weeks. Mild transient ocular inflammation was the most common post-injection adverse event.
The following reactions have been identified during post-marketing use of OZURDEX® in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to OZURDEX® , or a combination of these factors, include: complication of device insertion ( implant misplacement), device dislocation with or without corneal edema, endophthalmitis, hypotony of the eye (associated with vitreous leakage due to injection), and retinal detachment .