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Clin Ophthalmol. 2019 Feb 12;13:261-275. doi: 10.2147/OPTH.S189039. eCollection 2019.

A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease.

Author information

1
TopiVert Pharma Limited, London, UK, mike.taylor@topivert.com.
2
Ora Inc., Andover, MA, USA.
3
Andover Eye Associates, Andover, MA, USA.
4
Virginia Eye Consultants, Norfolk, VA, USA.

Abstract

Purpose:

To evaluate the safety and efficacy of topical TOP1630, a novel nonsystemic kinase inhibitor, in dry eye disease (DED).

Patients and methods:

A randomized, double-masked, parallel-group trial of 0.1% TOP1630 ophthalmic solution TID or placebo (vehicle without active drug) was conducted in DED subjects (n=61). Key eligibility criteria consistent with enrolling a moderate to severe DED population included >6 months DED history; OSDI© score ≥18; Schirmer's test score ≤10 and ≥1 mm/5 minutes; tear film break-up time >1 and <7 seconds; and dry eye exacerbation in corneal staining and ocular discomfort in a Controlled Adverse Environment (CAE®). After a 7-day run-in period with placebo TID, eligible subjects were randomized to TOP1630 or placebo for 28 days. No supplemental artificial tears or rescue medication were allowed.

Results:

TOP1630 was safe, well-tolerated, and efficacious in treating DED symptoms and signs. No serious adverse events (AEs) or withdrawals due to treatment emergent AEs occurred. Drop comfort scores showed TOP1630 to be comfortable and comparable with placebo. Significant symptom improvements were seen for TOP1630 vs placebo for ocular discomfort (P=0.02 post-CAE), grittiness/foreign body sensation (on four independent assessment scales, each P<0.05), worst DED symptom (diary, P=0.06), and ocular pain (VAS, P=0.03). Sign improvements were seen for total ocular surface (all regions), corneal sum, and conjunctival sum staining with TOP1630 compared with placebo (each P<0.05).

Conclusion:

TOP1630 had placebo-like tolerability and produced improvements in multiple symptom and sign endpoints in both environmental and challenge settings. The emergent TOP1630 benefit-risk profile for DED treatment is highly favorable and supports further development.

KEYWORDS:

DED; TOP1630; dry eye; ocular inflammation

Conflict of interest statement

Disclosure MT, CW, MCTF, AR, and SW are employees of TopiVert Pharma Limited. GO, JDS, and AD are consultants of TopiVert Pharma Limited. GO is an employee of Ora Inc. GT reports grants from TopiVert Pharma Limited, during the conduct of the study; grants from Oculeve, Allergan, ReGentree, Hanall, Mimetogen, AB2Bio, Aldeyra, Axerovision, BRIM, Diagnostear, Novaliq, Oyster point and grants, personal fees from Ora, Inc., outside the submitted work. MCTF reports personal fees from TopiVert Pharma Limited, outside the submitted work. MCTF has a patent US9499486 issued. JDS reports grants from TopiVert Pharma Limited, during the conduct of the study; grants from Allergan, Shire, Bausch & Lomb, Sun Pharma and Novaliq, outside the submitted work. The authors report no other conflicts of interest in this work.

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