Lawrence Brian D, Karpecki Paul M, Infanger David W, Levy Brian
From the Silk Technologies, Ltd. (B.D.L., D.W.I.), Maple Grove, Minnesota, USA.
Kentucky Eye Institute (P.M.K.), Lexington, Kentucky, USA.
Am J Ophthalmol. 2025 Jan;269:315-326. doi: 10.1016/j.ajo.2024.08.034. Epub 2024 Aug 31.
In this study the safety and efficacy of silk-derived protein 4 (SDP-4), also known as amlisimod, eye drops against a vehicle control formulation in patients with moderate to severe dry eye disease (DED) was assessed. SDP-4 is a novel, naturally derived, anti-inflammatory wetting agent that enhances coating on the ocular surface.
Exploratory Phase 2, 12- and 8-week, serial cohort, multicenter, double-masked, randomized, vehicle-controlled study.
In the first cohort (N = 305), patients were randomized 1:1:1:1 to SDP-4 (0.1%, 1%, 3% wt./wt.) or vehicle control and dosed 2 times per day (BID), while in the second cohort patients were randomized 1:1 with 1% wt./wt. SDP-4, the best performing formulation from the first cohort, or vehicle control BID (N = 151). Diagnosed DED patients were treated in the United States between April 2019 and May 2021. The first cohort of subjects had moderate to severe baseline symptoms, while the second cohort had moderate baseline symptoms to study the impact of baseline symptoms on SDP-4 performance. Key sign and symptom end points were mean change from baseline in TBUT and total SANDE score (0-100 visual analog scale) throughout the study.
SDP-4 (1%) significantly increased TBUT vs the vehicle control (P < .05) at days 28 and 56 in the first cohort, and patient symptomatology from baseline was reduced by 46% based on subject reported SANDE VAS scores at day 84. Patients with more severe baseline DED symptoms experienced a significantly greater amount of relief than when compared to patients with moderate DED (P < .05). All treatment groups were well tolerated with a 2.6% total discontinuation rate.
To the best of our knowledge, this was the first-in-human use of SDP-4 in a clinical trial. SDP-4 is a first-in-class protein ingredient that offers a safe and multi-modal treatment approach for alleviating severe DED symptoms within a novel formulation.
本研究评估了丝源蛋白4（SDP-4，也称为阿利西莫德）滴眼液相对于赋形剂对照制剂治疗中重度干眼症（DED）患者的安全性和有效性。SDP-4是一种新型的天然来源的抗炎性湿润剂，可增强眼表的覆盖。
探索性2期、为期12周和8周的系列队列、多中心、双盲、随机、赋形剂对照研究。
在第一个队列（N = 305）中，患者按1:1:1:1随机分为SDP-4（0.1%、1%、3%重量/重量）组或赋形剂对照组，每天给药2次（每日两次），而在第二个队列中，患者按1:1随机分为1%重量/重量的SDP-4组（第一个队列中表现最佳的制剂）或赋形剂对照组，每日两次（N = 151）。2019年4月至2021年5月期间，在美国对确诊的DED患者进行了治疗。第一个队列的受试者有中重度基线症状，而第二个队列有中度基线症状，以研究基线症状对SDP-4性能的影响。关键体征和症状终点是整个研究过程中泪膜破裂时间（TBUT）相对于基线的平均变化以及总SANDE评分（0-100视觉模拟量表）。
在第一个队列中，第28天和第56天时，SDP-4（1%）组的TBUT较赋形剂对照组显著增加（P < 0.05），根据受试者在第84天报告的SANDE视觉模拟量表评分，患者自基线以来的症状减轻了46%。与中度DED患者相比，基线DED症状更严重的患者缓解程度明显更大（P < 0.05）。所有治疗组耐受性良好，总停药率为2.6%。
据我们所知，这是SDP-4在临床试验中的首次人体应用。SDP-4是一流的蛋白质成分，在一种新型制剂中提供了一种安全且多模式的治疗方法，用于缓解严重的DED症状。
