Taylor Mike, Ousler George, Torkildsen Gail, Walshe Claire, Fyfe Matthew C T, Rowley Adele, Webber Steve, Sheppard John D, Duggal Ajay
TopiVert Pharma Limited, London, UK,
Ora Inc., Andover, MA, USA.
Clin Ophthalmol. 2019 Feb 12;13:261-275. doi: 10.2147/OPTH.S189039. eCollection 2019.
To evaluate the safety and efficacy of topical TOP1630, a novel nonsystemic kinase inhibitor, in dry eye disease (DED).
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.
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 (=0.02 post-CAE), grittiness/foreign body sensation (on four independent assessment scales, each <0.05), worst DED symptom (diary, =0.06), and ocular pain (VAS, =0.03). Sign improvements were seen for total ocular surface (all regions), corneal sum, and conjunctival sum staining with TOP1630 compared with placebo (each <0.05).
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.
评估新型非全身用激酶抑制剂TOP1630局部用药治疗干眼疾病（DED）的安全性和有效性。
在DED受试者（n = 61）中进行了一项随机、双盲、平行组试验，比较0.1% TOP1630眼药水每日三次（TID）与安慰剂（不含活性药物的赋形剂）。符合纳入中度至重度DED人群的关键入选标准包括：DED病史超过6个月；眼表疾病指数（OSDI）评分≥18；泪液分泌试验评分≤10且≥1毫米/5分钟；泪膜破裂时间>1秒且<7秒；以及在受控不良环境（CAE）中角膜染色出现干眼加重和眼部不适。在使用安慰剂每日三次进行7天导入期后，符合条件的受试者被随机分配至TOP1630组或安慰剂组，为期28天。不允许使用补充性人工泪液或急救药物。
TOP1630在治疗DED症状和体征方面安全、耐受性良好且有效。未发生严重不良事件（AE）或因治疗中出现的AE而停药的情况。滴眼液舒适度评分显示TOP1630使用舒适，与安慰剂相当。与安慰剂相比，TOP1630在眼部不适（CAE后P = 0.02）、沙砾感/异物感（在四个独立评估量表上，每个P<0.05）、最严重的DED症状（日记记录，P = 0.06）和眼部疼痛（视觉模拟评分，P = 0.03）方面症状有显著改善。与安慰剂相比，TOP1630在整个眼表（所有区域）、角膜染色总和及结膜染色总和方面有显著改善（每个P<0.05）。
TOP1630具有类似安慰剂的耐受性，并在环境和激发试验中多个症状和体征终点方面有所改善。新出现的TOP1630用于DED治疗的效益风险比非常有利，支持进一步研发。
