Elsevier

Ophthalmology

Volume 118, Issue 6, June 2011, Pages 1089-1097
Ophthalmology

Original article
Primary Endpoint Results of a Phase II Study of Vascular Endothelial Growth Factor Trap-Eye in Wet Age-related Macular Degeneration

Presented at: the Retina Society, October, 2009; American Academy of Ophthalmology Annual Meeting, October, 2009; International Symposium on Ocular Pharmacology and Therapeutics, December 2009; Association for Research in Vision and Ophthalmology Annual Meeting, April, 2010.
https://doi.org/10.1016/j.ophtha.2011.02.039Get rights and content

Objective

To evaluate the biologic effects and safety of vascular endothelial growth factor (VEGF) Trap-Eye during a 12-week fixed-dosing period in patients with neovascular (wet) age-related macular degeneration (AMD).

Design

Multicenter, prospective, randomized, double-masked clinical trial with initial 12-week fixed dosing period. Data were analyzed to week 16.

Participants

We included 159 patients with subfoveal choroidal neovascularization secondary to wet AMD.

Methods

Patients were randomized 1:1:1:1:1 to VEGF Trap-Eye during the fixed-dosing phase (day 1 to week 12): 0.5 or 2 mg every 4 weeks (0.5 mg q4wk, 2 mg q4wk) on day 1 and at weeks 4, 8, and 12; or 0.5, 2, or 4 mg every 12 weeks (0.5 mg q12wk, 2 mg q12wk, or 4 mg q12wk) on day 1 and at week 12.

Main Outcome Measures

The primary endpoint was change from baseline in central retinal/lesion thickness (CR/LT) at week 12; secondary outcomes included change in best-corrected visual acuity (BCVA), proportion of patients with a gain of ≥15 letters, proportion of patients with a loss of >15 letters, and safety.

Results

At week 12, treatment with VEGF Trap-Eye resulted in a significant mean decrease in CR/LT of 119 μm from baseline in all groups combined (P<0.0001). The reduction in CR/LT with the 2 mg q4wk and 0.5mg q4wk regimens was significantly greater than each of the quarterly dosing regimens. The BCVA increased significantly by a mean of 5.7 letters at 12 weeks in the combined group (P<0.0001), with the greatest mean gain of >8 letters in the monthly dosing groups. At 8 weeks, BCVA improvements were similar with 2 mg q4wk and 2 mg q12wk dosing. After the last required dose at week 12, CR/LT and visual acuity were maintained or further improved at week 16 in all treatment groups. Ocular adverse events were mild and consistent with safety profiles reported for other intraocular anti-VEGF treatments.

Conclusions

Repeated monthly intravitreal dosing of VEGF Trap-Eye over 12 weeks demonstrated significant reductions in retinal thickness and improvements in visual acuity, and was well-tolerated in patients with neovascular AMD.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Design

The primary objectives of the study were to assess the effect of intravitreal VEGF Trap-Eye on central retinal/lesion thickness (CR/LT) and to assess the ocular and systemic safety and tolerability of repeated doses of VEGF Trap-Eye in patients with CNV associated with wet AMD. A key secondary objective was to assess the effect of VEGF Trap-Eye on BCVA.

The CLEAR-IT 2 was a prospective, double-masked, randomized study conducted at 33 sites in the United States. Patients were enrolled between May

Disposition

Patient disposition is shown in Table 1. Among the 159 patients who were randomized, 157 received treatment. Two patients, 1 each in the 2-mg monthly and 2-mg quarterly groups, were withdrawn before receiving treatment. Of the 157 patients who received treatment, 152 (96.8%) completed the 12-week visit, and 5 patients were withdrawn. Reasons for withdrawal were death (n = 1, 4q12 group), AE (n = 1, 2q12 group), inability to attend visits (n = 1, 2q12 group), investigator decision (n = 1, 0.5q12

Discussion

During the 12-week fixed-dosing period of this phase 2 study, intravitreally administered VEGF Trap-Eye demonstrated significant anatomic and visual improvements from baseline at week 12 after repeated monthly dosing. Treatment with VEGF Trap-Eye 0.5 mg and 2 mg dosed every 4 weeks resulted in the greatest improvements in both measures at the 12-week endpoint. The CR/LT decreased by a mean of −153.5 and −169.2 μm from baseline, and BCVA mean letter score improved by 8.8 and 8.3 letters with

Acknowledgments

Technical writing and editorial assistance was provided by Meher Dustoor, PhD.

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    Manuscript no. 2010-1365.

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

    David M. Brown – Alcon Laboratories – Consultant, Grant/Financial Support; Alimera – Grant/Financial Support; Allergan – Consultant, Grant/Financial Support; Carl Zeiss Meditec – Consultant; CoMentis – Grant/Financial Support; Eyemaginations – Consultant; Genentech – Consultant, Grant/Financial Support, Lecturer; Heidelberg Engineering – Consultant, Lecturer; Jerini Ophthalmics – Consultant, Grant/Financial Support, Lecturer; NeoVista – Consultant, Grant/Financial Support, Lecturer; Neurotech – Grant/Financial Support; Novartis Pharmaceuticals – Consultant, Grant/Financial Support; Oraya Therapeutics – Consultant; Othera – Grant/Financial Support; Oxigene – Grant/Financial Support; Pfizer Ophthalmics – Consultant, Grant/Financial Support; Regeneron – Consultant, Grant/Financial Support, Lecturer; Steba – Consultant.

    Jeffrey S. Heier: Acucela – Consultant; Alcon Laboratories – Consultant, Grant/Financial Support; Allergan – Consultant, Grant/Financial Support; Bausch & Lomb – Consultant; CoMentis – Grant/Financial Support; Eyemaginations – Consultant; Fovea – Consultant; Genentech – Consultant, Grant/Financial Support, Lecturer; Genzyme – Consultant; Heidelberg Engineering – Consultant, Lecturer; iScience – Consultant, Grant/Financial Support; Ista Pharmaceuticals – Consultant, Grant/Financial Support; Jerini Ophthalmics – Consultant, Grant/Financial Support, Lecturer; LPath – Consultant; NeoVista – Consultant, Grant/Financial Support, Lecturer; Neurotech – Grant/Financial Support; Notal Vision – Consultant; Novartis Pharmaceuticals – Consultant, Grant/Financial Support; Optherion – Consultant; Optimedica – Royalties; Oraya Therapeutics – Consultant; Oxigene – Grant/Financial Support; Paloma – Consultant, Grant/Financial Support; Pfizer Ophthalmics – Consultant, Grant/Financial Support; Regeneron – Consultant, Grant/Financial Support, Lecturer; Resolvyx Pharmaceuticals – Consultant; Schering Plough Research Institute – Consultant; Scyfix – Consultant; Steba – Consultant; VisionCare Ophthalmic Technologies – Consultant, Grant/Financial Support.

    Thomas Ciulla: Neovista – Consultant; Regeneron – Consultant; Pfizer – Consultant; Genentech – Grant/Financial Support; Regeneron – Grant/Financial Support; Allergan – Grant/Financial Support; Alimera – Grant/Financial Support; Othera – Grant/Financial Support; Glaxo-Smith-Kline – Grant/Financial Support; Optko – Grant/Financial Support; National Eye Institute/National Institutes of Health – Grant/Financial Support.

    Prema Abraham: Genentech – Consultant, Grant/Financial Support; Alcon – Consultant, Grant/Financial Support; Novartis – Consultant, Grant/Financial Support; Regeneron – Grant/Financial Support; Allergan – Grant/Financial Support; Opko Health – Grant/Financial Support; Jerini Ophthalmic – Grant/Financial Support; Pfizer – Grant/Financial Support; Eli Lilly – Grant/Financial Support; Alimera – Grant/Financial Support; VRT – Grant/Financial Support; Schering-Plough – Grant/Financial Support.

    George Yancopoulous, Neil Stahl, Avner Ingerman, Robert Vitti, Alyson J. Berliner, Ke Yang: Regeneron – Employee at the time the study was conducted.

    Quan Dong Nguyen: Bausch & Lomb – Consultant; Genentech – Grant/Financial Support; Regeneron – Grant/Financial Support.

    Supported by Regeneron Pharmaceuticals, Inc. and Bayer HealthCare AG. The sponsors participated in the design of the study, conducting the study, data collection, data management, data analysis, interpretation of the data, and the preparation, review, and approval of the manuscript.

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