A Multi-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Efficacy and Safety of TOP1630 0.1% Ophthalmic Solution Compared to Placebo in Subjects With Moderate to Severe Dry Eye Syndrome

In subjects with Dry Eye Syndrome (DES):
The primary objective of this study is to confirm the efficacy of TOP1630 0.1% Ophthalmic Solution TID OU compared to placebo treatment at Day 29 on pre-specified sign and symptom endpoints in subjects with moderate to severe DES.

Start Date13 Feb 2019

Sponsor / Collaborator

Topivert Pharma Ltd.

NCT03088605 / CompletedPhase 2

A Single-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Safety and Efficacy of TOP1630 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Syndrome

In subjects with Dry Eye Syndrome:
The primary objective of this study is to compare the safety and tolerability of TOP1630 Ophthalmic Solution to placebo.
The secondary objectives are to compare the efficacy of TOP1630 Ophthalmic Solution to placebo for the treatment of the signs and symptoms of dry eye syndrome.

Start Date20 Feb 2017

Sponsor / Collaborator

Beijing Orange Xin Data Technology Co., Ltd

[+1]

100 Clinical Results associated with p38 MAPK x LCK x Syk x SRC

100 Translational Medicine associated with p38 MAPK x LCK x Syk x SRC

0 Patents (Medical) associated with p38 MAPK x LCK x Syk x SRC

Literatures (Medical) associated with p38 MAPK x LCK x Syk x SRC

15 Mar 2018·Investigative Opthalmology & Visual ScienceQ2 · MEDICINE

Narrow Spectrum Kinase Inhibitors Demonstrate Promise for the Treatment of Dry Eye Disease and Other Ocular Inflammatory Disorders

Q2 · MEDICINE

ArticleOA

Author: Foster, Martyn R. ; Hagan, Suzanne ; Taylor, Mike ; Fyfe, Matthew C. T. ; Doughty, Michael ; Webber, Steve ; Walshe, Claire A. ; Ofori-Frimpong, Boatemaa ; Rowley, Adele ; Solanke, Yemisi ; Oliver, Katherine ; Sirohi, Sameer

PurposeThe purpose of this study is to determine the potential of narrow spectrum kinase inhibitors (NSKIs) to treat inflammatory eye disorders.MethodsHuman conjunctival epithelial (HCE) cells were retrieved from subjects via impression cytology. Real-time quantitative PCR (qPCR) was performed on HCE cells to determine gene expression of NSKI kinase targets and proinflammatory cytokines in dry eye disease (DED) patients versus healthy controls. qPCR also assessed p38α expression in hyperosmolar-treated Chang conjunctival epithelial cells. Interaction of NSKI TOP1362 with the kinases was evaluated in ATP-dependent Z-LYTE and competition binding assays. Anti-inflammatory activity was assessed in human peripheral blood mononuclear cells and primary macrophages. In an endotoxin-induced uveitis (EIU) study, lipopolysaccharide (LPS) was administered intravitreally to Lewis rats. TOP1362, dexamethasone, or vehicle was administered topically, and inflammatory cytokine levels were measured 6 hours after LPS injection.ResultsHCE cells from DED patients showed significantly increased expression of p38α, spleen tyrosine kinase (Syk), Src, lymphocyte-specific protein tyrosine kinase (Lck), interleukin one beta (IL-1β), interleukin eight (IL-8), monocyte chemotactic protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9). TOP1362 strongly inhibited the kinase targets p38α, Syk, Src, and Lck, blocked the rise in p38α expression in hyperosmolar Chang cells, and potently reduced inflammatory cytokine release in cellular models of innate and adaptive immunities. In the EIU model, TOP1362 dose-dependently attenuated the LPS-induced rise in inflammatory cell infiltration and ocular cytokine levels with efficacy comparable to that of dexamethasone.ConclusionsTOP1362 is a potent inhibitor of kinases upregulated in DED and markedly attenuates proinflammatory cytokine release in vitro and in vivo, highlighting the therapeutic potential of NSKIs for treating ocular inflammation, such as that observed in DED.

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