Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration: A Phase I/II Multicenter, Controlled, Multidose Study
Presented in part at: American Society of Retinal Specialists Annual Meeting, August, 2003; New York, New York, and American Academy of Ophthalmology Annual Meeting, November, 2003; Anaheim, California.
Received 24 May 2005; accepted 20 October 2005. published online 14 February 2006.
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.
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.
1Ophthalmic Consultants of Boston, Boston, Massachusetts
2Charlotte Eye, Ear, Nose, & Throat Associates, Charlotte, North Carolina
3University of South Florida College of Medicine, Tampa, Florida
4Retina Vitreous Center, New Brunswick, New Jersey
5Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida
Reprint requests to Jeffrey S. Heier, MD, Ophthalmic Consultants of Boston, 50 Staniford Street, Suite 600, Boston, MA 02114
Manuscript no. 2005-448.
This study was supported by Genentech, Inc., South San Francisco, California.
Financial disclosure/conflict of interest: Drs Heier, Antoszyk, Rosenfeld, and Gentile have served on the Lucentis Advisory Board; Dr Pavan has served as a consultant to Genentech for Lucentis; and Drs Sy, Hantsbarger, and Shams are employees of Genentech, Inc.
ABSTRACT