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

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.

Efficacy of Lifitegrast Ophthalmic Solution, 5.0%, in Patients With Moderate to Severe Dry Eye Disease

“…Artificial tears are the first-line treatment for DED and are designed to provide temporary symptomatic relief without addressing the underlying cause of inflammation. 13,16 However, artificial tear use is usually continued in all stages of DED in conjunction with other treatments. 38 Although artificial tear use was required to be discontinued before enrollment in the OPUS-2 and OPUS-3 studies, 9,10 Atallah et al 39 reported a significant improvement in the signs and symptoms of chronic DED with lifitegrast in a 6-month retrospective study, even in patients with concurrent use of artificial tears.…”

“…9,10 The EDS was measured with a VAS, which is an established symptom measure in DED. 16,17 Corneal fluorescein staining was performed with 2% unpreserved sodium fluorescein solution. Grading of corneal fluorescein staining was based on the Expanded National Eye Institute/Industry Workshop Corneal Fluorescein Staining Scale and methods modified from Lemp (1995) 18 and Shimmura et al (1995).…”

“…The EDS was measured with a VAS, which is an established symptom measure in DED . Corneal fluorescein staining was performed with 2% unpreserved sodium fluorescein solution.…”

Management of Sjogren’s Dry Eye Disease—Advances in Ocular Drug Delivery Offering a New Hope

“…This treatment was shown to be equivalent to placebo in terms of safety and tolerability. While the primary endpoint was not evaluation of TOP1360 efficacy in treatment of DED, significant improvement was observed by day 15 of treatment in patients receiving TOP1360, with patients reporting relief in ocular dryness, ocular discomfort, foreign body discomfort and grittiness [ 56 ].…”

A Randomised Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Palovarotene Ophthalmic Solution

“…Of these, only a cyclosporine 1 mg/mL emulsion is approved for the treatment of DED in Europe [ 9 ]. However, cyclosporine and lifitegrast have limited efficacy and a slow onset for some patients [ 10 , 11 ]. Ocular burning is a common side effect of topical cyclosporine (occurring in up to 17% of patients) and is the most common reason for discontinuing treatment by patients [ 5 , 6 ].…”