A Phase IIIb Study to Evaluate the Safety of Ranibizumab in Subjects with Neovascular Age-related Macular Degeneration

doi:10.1016/j.ophtha.2009.05.024

Ophthalmology

Volume 116, Issue 9, September 2009, Pages 1731-1739

These data were presented at the American Academy of Ophthalmology, November 2008.

https://doi.org/10.1016/j.ophtha.2009.05.024 Get rights and content

Objective

To evaluate the safety and efficacy of intravitreal ranibizumab in a large population of subjects with neovascular age-related macular degeneration (AMD).

Design

Twelve-month randomized (cohort 1) or open-label (cohort 2) multicenter clinical trial.

Participants

A total of 4300 subjects with angiographically determined subfoveal choroidal neovascularization (CNV) secondary to AMD.

Methods

Cohort 1 subjects were randomized 1:1 to receive 0.3 mg (n = 1169) or 0.5 mg (n = 1209) intravitreal ranibizumab for 3 monthly loading doses. Dose groups were stratified by AMD treatment history (treatment-naïve vs. previously treated). Cohort 1 subjects were retreated on the basis of optical coherence tomography (OCT) or visual acuity (VA) criteria. Cohort 2 subjects (n = 1922) received an initial intravitreal dose of 0.5 mg ranibizumab and were retreated at physician discretion. Safety was evaluated at all visits.

Main Outcome Measures

Safety outcomes included the incidence of ocular and nonocular adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes included changes in best-corrected VA over time.

Results

Some 81.7% of cohort 1 subjects and 49.9% of cohort 2 subjects completed the 12-month study. The average total number of ranibizumab injections was 4.9 for cohort 1 and 3.6 for cohort 2. The incidence of vascular and nonvascular deaths during the 12-month study was 0.9% and 0.7% in the cohort 1 0.3 mg group, 0.8% and 1.5% in the cohort 1 0.5 mg group, and 0.7% and 0.9% in cohort 2, respectively. The incidence of death due to unknown cause was 0.1% in both cohort 1 dose groups and cohort 2. The number of vascular deaths and deaths due to unknown cause did not differ across cohorts or dose groups. Stroke rates were 0.7%, 1.2%, and 0.6% in the 0.3 mg and 0.5 mg groups and cohort 2, respectively. At month 12, cohort 1 treatment-naïve subjects had gained an average of 0.5 (0.3 mg) and 2.3 (0.5 mg) VA letters and previously treated subjects had gained 1.7 (0.3 mg) and 2.3 (0.5 mg) VA letters.

Conclusions

Intravitreal ranibizumab was safe and well tolerated in a large population of subjects with neovascular AMD. Ranibizumab had a beneficial effect on VA. Future investigations will seek to establish optimal dosing regimens for persons with neovascular AMD.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Materials and Methods

SAILOR was a 12-month, multicenter, phase IIIb study intended to further characterize the safety and efficacy profiles of intravitreal ranibizumab. Protocols were approved by the institutional review board at each study site, and the study was conducted according to the International Conference on Harmonisation E6 Guideline for Good Clinical Practice and any national requirements. All subjects provided informed consent before participation in the study. The SAILOR study is registered at //www.clinicaltrials.gov

Results

From November 2005 to June 30, 2006 (when ranibizumab was approved for the treatment of neovascular AMD by the Food and Drug Administration), 2378 cohort 1 subjects were randomly assigned to receive 0.3 mg (n = 1169) or 0.5 mg (n = 1209) intravitreal ranibizumab at 105 US centers. Cohort 1 subjects had an average age of 79 years, and 59% were female (Table 1). Approximately 60% of cohort 1 subjects in each dose group had been previously treated for AMD. The types of previous treatment were

Discussion

SAILOR is the largest study to date to evaluate safety (primary objective) and efficacy (secondary objective) of intravitreal ranibizumab in a population of subjects with CNV secondary to AMD. Ranibizumab was well tolerated, and the incidence of ocular SAEs and AEs was low and unrelated to dose. The rates of key nonocular SAEs and AEs, including APTC ATEs, MI, and vascular death, were similar across cohorts and dose groups.

The incidence of stroke in SAILOR was similar to that observed in

Acknowledgment

We thank Naveed Shams, MD, PhD, for contributions to the design and conduct of the study.

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Ranibizumab for neovascular age-related macular degeneration
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Ranibizumab versus verteporfin for neovascular age-related macular degeneration
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There are more references available in the full text version of this article.

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: Manuscript no. 2008-1521.

Financial Disclosure(s): The author(s) have made the following disclosure(s):

Genentech, Inc. (South San Francisco, California) provided support for the study and participated in study design; conducting the study; data collection, management, analysis, and interpretation; and manuscript preparation, review, and approval. David M. Boyer, consultant and lecturer for Genentech, Alcon, Pfizer, and Novartis. Jeffrey S. Heier, consultant and lecturer for Genentech, Regeneron, Jerini Ophthalmic, NeoVista, and ISTA; consultant for iScience, Pfizer, VisionCare, Allergan, Paloma, and Oxigene. David M. Brown, consultant and lecturer for Genentech, Alcon, and Regeneron; consultant for Novartis and Neovista. Steven F. Francom, employee of Genentech. Tsontcho Ianchulev, employee of Genentech. Roman G. Rubio, employee and equity owner, Genentech. Roberta Kelly, an employee and equity owner of Genentech, Inc., who is not an author and did not contribute to the scientific content of the manuscript, provided general writing and editorial assistance.

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Original articleA Phase IIIb Study to Evaluate the Safety of Ranibizumab in Subjects with Neovascular Age-related Macular Degeneration

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Materials and Methods

Results

Discussion

Acknowledgment

Ophthalmology

Ranibizumab for neovascular age-related macular degeneration

N Engl J Med

Ranibizumab versus verteporfin for neovascular age-related macular degeneration

N Engl J Med

Original article
A Phase IIIb Study to Evaluate the Safety of Ranibizumab in Subjects with Neovascular Age-related Macular Degeneration