Ranibizumab for treatment of neovascular age-related macular degeneration: a phase I/II multicenter, controlled, multidose study.
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.


METHODS
Multicenter, controlled, open-label, clinical trial.


METHODS
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.


METHODS
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 > or =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 > or =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.
Ophthalmic Consultants of Boston, Boston, Massachusetts 02114, USA.
Jeffrey S
JS
Heier
Andrew N
AN
Antoszyk
Peter Reed
PR
Pavan
Steven R
SR
Leff
Philip J
PJ
Rosenfeld
Thomas A
TA
Ciulla
Richard F
RF
Dreyer
Ronald C
RC
Gentile
Judy P
JP
Sy
Gary
G
Hantsbarger
Naveed
N
Shams
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology; D018592:Cross-Over Studies; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D007267:Injections; D007429:Intraocular Pressure; D008268:Macular Degeneration / Q000150:complications / Q000188:drug therapy*; D008297:Male; D000069579:Ranibizumab; D019233:Retreatment; D014792:Visual Acuity / Q000502:physiology; D014822:Vitreous Body
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069579:Ranibizumab