Original articlePrimary Endpoint Results of a Phase II Study of Vascular Endothelial Growth Factor Trap-Eye in Wet Age-related Macular Degeneration
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 Two patients, 1 each in the 2-mg monthly and 2-mg quarterly groups, were withdrawn before receiving treatment. Of the 157 patients who received treatment, 152 (96.8%) completed the 12-week visit, and 5 patients were withdrawn.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.
References (29)
- et al.
Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo
Exp Eye Res
(2007) - et al.
Use of soluble recombinant decoy receptor vascular endothelial growth factor trap (VEGF Trap) to inhibit vascular endothelial growth factor activity
Clin Colorectal Cancer
(2004) - et al.
The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing
Ophthalmology
(2011) - et al.
Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study
Arch Ophthalmol
(1998) Prevalence of age-related macular degeneration in the United States
Arch Ophthalmol
(2004)- et al.
Age-related macular degeneration and blindness due to neovascular maculopathy
Arch Ophthalmol
(1984) - et al.
Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor
Invest Ophthalmol Vis Sci
(1996) - et al.
Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate
Arch Ophthalmol
(1996) - et al.
Increased expression of angiogenic growth factors in age-related maculopathy
Br J Ophthalmol
(1997) - et al.
Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment
Arch Ophthalmol
(2002)
Vascular endothelial growth factor biology: clinical implications for ocular treatments
Br J Ophthalmol
Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization
Invest Ophthalmol Vis Sci
Vascular endothelial growth factor Trap-Eye for diabetic macular oedema
Br J Ophthalmol
VEGF receptor signalling—in control of vascular function
Nat Rev Mol Cell Biol
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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.