Maximum tolerated dose of a humanized anti-vascular endothelial growth factor antibody fragment for treating neovascular age-related macular degeneration

被引:186
作者
Rosenfeld, PJ
Schwartz, SD
Blumenkranz, MS
Miller, JW
Haller, JA
Reimann, JD
Greene, WL
Shams, N
机构
[1] Univ Miami, Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA
[2] Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90024 USA
[3] Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA
[4] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA
[5] Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD 21218 USA
[6] Genentech Inc, San Francisco, CA 94080 USA
关键词
D O I
10.1016/j.ophtha.2005.01.043
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: To investigate the maximum tolerated dose of ranibizumab administered as a single intravitreal injection. Design: Open-label, 5-center, uncontrolled, prospective, dose-ranging, interventional case series. Participants: Twenty-seven patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) with best-corrected Snellen equivalent visual acuity (VA) of 20/100 or worse and considered ineligible for laser photocoagulation or photodynamic therapy. Methods: A single intravitreal injection of ranibizumab was to be administered at 1 of 6 escalating doses (50, 150, 300, 500, 1000, and 2000 fig), with escalation to the next dose level occurring only after the safety and tolerability of the lower dose level was established through postinjection day 14. Follow-up examinations were performed on postinjection days 1, 3, 7, 14, 42, and 90. Enrollment was stopped if >= 2 patients experienced dose-limiting toxicity. Main Outcome Measures: The primary safety measures were changes from baseline in VA, intraocular pressure (IOP), intraocular inflammation, and production of antiranibizumab antibody. Dose-limiting toxicity was defined by intraocular inflammation, elevated IOP, reduced VA, or hemorrhage within 90 days after injection. Results: All patients completed this single intravitreal injection study, and 500 mu g of ranibizumab was the maximum tolerated dose. At the higher dose of 1000 mu g, significant intraocular inflammation was noted. All adverse events were self-limited, and no infectious endophthalmitis occurred. Aqueous or vitreous ocular inflammation occurred in 12 subjects, with complete resolution within 42 days. In 9 of the subjects, the inflammation was graded as trace to 1 + and required no treatment; in 3 of the subjects, the inflammation was graded as 2+ or3+, and 2 of the 3 were treated with topical 1% prednisolone acetate. No serum antiranibizumab antibodies were detected. All patients had VA similar or improved compared with baseline values. Conclusion: The maximum tolerated single dose of ranibizumab in neovascular AMD patients was 500 mu g. Single intravitreal injections of ranibizumab up to a dose of 500 mu g were safe and well tolerated in this small group of patients.
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页码:1048 / 1053
页数:6
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