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 > 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.

• Authors: Jeffrey S Heier, Andrew N Antoszyk, Peter Reed Pavan, Steven R Leff, Philip J Rosenfeld, Thomas A Ciulla, Richard F Dreyer, Ronald C Gentile, Judy P Sy, Gary Hantsbarger, Naveed Shams
• Journal: Ophthalmology (Ophthalmology) Vol. 113 Issue 4 Pg. 633.e1-4 (Apr 2006) ISSN: 1549-4713 [Electronic] United States
• PMID: 16483659 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Ranibizumab

Topics

• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Choroidal Neovascularization (drug therapy, etiology)
• Cross-Over Studies
• Female
• Fluorescein Angiography
• Follow-Up Studies
• Fundus Oculi
• Humans
• Injections
• Intraocular Pressure
• Macular Degeneration (complications, drug therapy)
• Male
• Ranibizumab
• Retreatment
• Visual Acuity (physiology)
• Vitreous Body