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Charles D Blizzard, Chintan Patel, Jeremy Hartman, Sean Serell, Kevin Yeh, Andrew Vanslette, Peter K Jarrett, Michael Goldstein, Rabia Gurses-Ozden; Safety and Pharmacodynamic Assessment of Repeated Intracameral Travoprost Implant Administration in Beagle Dogs. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2852 – A0375.
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Hydrogel-based, intracameral travoprost implant (OTX-TIC) is designed to deliver sustained-release travoprost to the anterior chamber for the treatment of glaucoma and is currently in a Phase 2 clinical trial. The purpose of this study was to evaluate the safety, tolerability and pharmacodynamic (PD) profile of repeated OTX-TIC administrations in a canine model.
Normotensive female beagle dogs received either one placebo vehicle implant (Group 1), one 26 µg OTX-TIC (Group 2), two 26 µg OTX-TIC (Group 3) or one 13 µg OTX-TIC (Group 4) implant injected intracamerally into the right eye (n = 8/group). Groups 1, 2 and 3 were dosed on Days 1 and 127, and Group 4 was dosed on Days 1, 57, 113, and 169. Group 2 represented an intended clinical dose and Group 3 provided a 2X dose multiple and 2X implant safety factor for travoprost drug and implant biomaterial. Group 4 used a shorter persisting hydrogel with a daily travoprost dose comparable to Group 2. Intraocular pressure (IOP), endothelial cell count and corneal thickness were collected. Ocular exams were performed with slit lamp and graded using a modified Hackett-McDonald Scoring System which included conjunctival hyperemia (0 = normal to 3 = severe) and pupillary reflex (0 = normal to 3 = miotic pupil).
OTX-TIC was well-tolerated following repeated administration through 30 weeks. No signs of intraocular inflammation (aqueous cell or flare, vitreous cell) were observed in any eyes of all groups during the study. Mean reduction in IOP (standard deviation) compared to baseline was 7.7% (10.2), 25.7% (13.4), 25.3% (16.2), and 31.0% (12.0) for Groups 1, 2, 3 and 4, respectively throughout the study period. Conjunctival hyperemia and miosis, both known PD responses to travoprost in dogs, were observed in OTX-TIC treated eyes for 30 weeks. Mean conjunctival hyperemia scores and pupillary reflex scores were higher in OTX-TIC treated eyes (Groups 2, 3 and 4) compared to placebo vehicle (Group 1) at all study timepoints.
Multiple, repeated OTX-TIC administrations were generally safe and well-tolerated with no signs of inflammation observed and produced a clinically meaningful reduction in IOP through 30 weeks in beagles. OTX-TIC is currently being investigated in a Phase 2 clinical trial in the US.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
Mean Reduction in Intraocular Pressure from Baseline
Mean Conjunctival Hyperemia and Pupillary Reflex Scores
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