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Mike Taylor, Ajay Duggal, Claire Walshe, Matthew Fyfe, Adele Rowley, Steve Webber; A Phase 2 randomized, double-masked, placebo-controlled study of novel narrow spectrum kinase inhibitor TOP1630 for the treatment of dry eye syndrome. Invest. Ophthalmol. Vis. Sci. 2018;59(9):947.
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© ARVO (1962-2015); The Authors (2016-present)
Dry Eye Syndrome (DES) is a common multifactorial condition with major impact on vision and quality of life. Inflammation has an important role in DES pathophysiology. TOP1630, a novel narrow spectrum kinase inhibitor (NSKI), selectively targets key kinases fundamental to inflammatory cell signalling in innate and adaptive immune responses. This Phase 2 study evaluated the safety and efficacy of topical TOP1630 in subjects with DES.
A randomized, double-masked, parallel-group trial of 0.1% TOP1630 topical ophthalmic solution TID or placebo was conducted in DES subjects (n=61). Key eligibility criteria, consistent with a moderate to severe DES population, included exacerbation in corneal staining and ocular discomfort in a Controlled Adverse Environment (CAE®; Ora, Inc.) challenge. After a 7-day run-in with placebo TID, eligible subjects were randomized to 28 days treatment. No supplemental artificial tears were allowed. Safety assessments included adverse event (AE) query, slit-lamp biomicroscopy and visual acuity. Efficacy assessments included environmental and CAE® change in DES symptoms and ocular surface staining. Analyses reported are pre-specified (i.e. there were no post hoc or subgroup analyses).
TOP1630 was safe, well tolerated and efficacious in treating DES symptoms and signs. No Serious AEs and no withdrawals due to treatment emergent AEs occurred. Drop comfort scores showed TOP1630 to be comfortable and comparable to placebo. Symptoms showing significant improvements for TOP1630 versus placebo included improvement in worst DES symptom (diary, p=0.03), ocular discomfort (p=0.02 CAE® only), grittiness/foreign body sensation (on 4 independent assessment scales, each p<0.05) and ocular pain (p=0.02). Total ocular surface (all-regions), corneal sum and conjunctival sum staining improved with TOP1630 compared to placebo (each p<0.05).
TOP1630 demonstrated an excellent safety and efficacy profile in subjects with DES. TOP1630 showed placebo-like tolerability and provided improvements in multiple symptom and sign endpoints in both environmental and challenge settings. Overall, the emergent benefit-risk profile for TOP1630 for the treatment of DES is highly favorable compared to existing treatments and supports advancement to later stage development.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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