Purchase this article with an account.
Vladimir Bantseev, Rebecca Erickson, Melissa Cheu, Caroline Amaya, Consuelo Alcalde, Yi Zhang, Joseph Beyer; Anti-Factor D Fab: In vivo Effects Following Intravitreous Administration to Cynomolgus Monkeys. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5657.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To characterize Anti-fD, a recombinant, humanized monoclonal Fab fragment directed against factor D in vivo effects following intravitreous (IVT) administration to cynomolgus monkeys.
Male and female cynomolgus monkeys were randomly assigned to dose groups of Anti-fD (0, 1, 3, 5 and 10 mg/eye/dose). Animals received a single or repeated dose (given once every 3 weeks for 10 total doses). Each dose was given as two bilateral IVT injections 15 minutes apart. Ocular toxicity was assessed by clinical ophthalmic examinations (OE), intraocular pressure measurements (IOP), ocular photography (OP), electroretinography (ERG), fluorescein angiography (FA), optical coherence tomography (OCT), and ocular anatomic pathology.
Systemic exposure to Anti-fD generally increased with the increase in dose level for single and repeat dose studies. The increases in mean Cmax and AUC values were roughly dose proportional. No accumulation of Anti-fD was observed following 10 doses of Anti-fD. In general, drug exposures were not affected by anti-therapeutic antibody (ATA) and ATA negative animals had similar exposure. OE evaluations showed Anti-fD as a single dose up to 10 mg/eye/dose or as a repeat dose up to 3 mg/eye/dose for 10 doses was were well tolerated. With repeat dosing at the highest dose variable ocular inflammatory response was seen and Anti-fD -related ophthalmic findings included severe anterior and posterior uveitis in two animals (after the sixth or the eighth dose). Drug-related microscopic findings consisted of ocular infiltrates including plasma cells within multiple structures in the eyes. No Anti-fD -related effects were noted on IOP or during ERG, OP, FA, or OCT evaluations.
Single dose administration of Anti-fD was well tolerated up to highest dose tested. Repeated dose administration was tolerated up to 3 mg/eye/dose. The anterior and posterior ocular inflammation at the highest dose in 2 animals after repeated dosing was likely the consequence of immune response to a heterologous protein. These findings were not observed in the Phase Ia single dose clinical study. A repeat dose Phase Ib/II is currently on-going.
This PDF is available to Subscribers Only