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E. Zimmer, B.J. Christian, P.E. Miller, M.T. Nork, J.N. VerHoeve, C.J. Murphy, J.M. Miller, R.A. Leedle, J. Lesniak, E. Bentley; Safety Evaluation of Intravitreal Administration of VEGF Trap in Cynomolgus Monkeys for 13 Weeks . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1751.
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This study was conducted to evaluate the safety of VEGF Trap, a potent VEGF inhibitor composed of portions of the extracellular domains of human VEGF receptors–1 and –2 fused to the Fc segment of IgG1.
VEGF Trap was given by intravitreal (IVT) injection once every 4 weeks to cynomolgus monkeys for 13 weeks. Animals (4/sex/group) were given bilateral IVT injections of vehicle (control) or VEGF Trap at 50, 250, or 500 mcg/eye on the first day of Weeks 1, 5, 9, and 13. Two additional animals/sex in the control and two highest dose groups were evaluated for 10 weeks after the final dose. Slit–lamp biomicroscopic, indirect ophthalmoscopic and intraocular pressure (IOP) evaluations were done at least weekly during treatment. Scotopic and photopic electroretinography (ERG) tests (Weeks 6, 10 and 21), and fundus photography/fluorescein angiography (Weeks 7 and 22) were performed. Clinical observations, body weight and clinical pathology tests were also assessed and ocular and nonocular tissues were evaluated microscopically.
Mild ocular inflammation (cell score generally 1+ or less; maximum 2+) was observed in the anterior chamber (AC) and vitreous. The transient AC response was greatest at 2 days postdose. By 4 weeks after each dose, AC cell had completely resolved in all animals, except one given 500 mcg/eye (trace level). Although the response was only mildly greater than that of controls, there was a weak trend for an increase in incidence of inflammation with dose. There was no accumulation of the vitreal cells with successive doses. No test article–related effects on IOP, or ERG tests were noted, and no evidence for test article–related toxicity was found following photographic, fluorescein angiographic, or histomorphologic evaluations.
VEGF Trap up to 500 mcg/eye, (4 doses) was well tolerated, and a four–week dosing interval allowed for complete or near–complete resolution of the mild inflammatory response.
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