Lacripep for the Treatment of Primary Sjögren-Associated Ocular Surface Disease: Results of the First-In-Human Study.
Lacripep for the Treatment of Primary Sjögren-Associated Ocular Surface Disease: Results of the First-In-Human Study.
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DOI：
10.1097/ico.0000000000003091
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发表时间：
2023-07-01
期刊：
影响因子：
2.8
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究的目的是评估活性19个氨基酸的lacritin片段（Lacripep）（一种广泛的眼表稳态调节剂）治疗原发性干燥综合征相关眼表疾病的安全性、耐受性、剂量和疗效。204例受试者随机接受溶媒、22 μM Lacripep或44 μM Lacripep，每日3次，持续28天，之前为14天导入期，随后为14天洗脱期。结果指标为角膜荧光素染色（CFS）、丽丝胺结膜染色、麻醉下的Schirmer、泪膜破裂时间、桑德评分和症状的视觉模拟量表评估。本研究确定了Lacripep局部治疗原发性干燥综合征患者的安全性和耐受性。不良事件很少：只有不到3%的患者服用Lacripep后出现轻度刺激。总CFS和眼干燥评分在第28天没有显著变化。对基线时眼干燥严重程度评分为60或更高的患者进行事后分析，发现14天和28天时下CFS显著改善，14天时烧灼感和刺痛感明显改善。在第14天和第28天观察到局部丽丝胺结膜染色显著改善。这项首次在原发性干燥综合征患者中进行的Lacripep人体研究表明，特定体征和症状有临床显著改善，可作为未来研究的基础。本研究确定了中重度疾病患者的安全性和耐受性以及潜在疗效指标。目前正在进一步研究适当的剂量和浓度。
The purpose of this study was to assess the safety, tolerability, dosing, and efficacy of the active 19 amino acid fragment of lacritin (Lacripep), a broad regulator of ocular surface homeostasis, in the treatment of ocular surface disease associated with primary Sjögren syndrome. Two hundred four subjects were randomized to receive vehicle, 22 μM Lacripep, or 44 μM Lacripep 3 times daily for 28 days, preceded by a 14-day run-in and followed by 14-day washout. Outcome measures were corneal fluorescein staining (CFS), lissamine conjunctival staining, Schirmer with anesthesia, tear break-up time, SANDE scoring, and visual analog scale assessment of symptoms. This study established the safety and tolerability of topical treatment with Lacripep in patients with primary Sjögren syndrome. There were few adverse events: Only mild irritation was found in less than 3 percent of patients dosed with Lacripep. Total CFS and Eye Dryness Score were not significantly changed at day 28. Post hoc analysis of patients with Eye Dryness Severity scores of 60 or greater at baseline revealed significant improvements in inferior CFS at 14 and 28 days and complaints of burning and stinging at 14 days. Significant improvement in regional lissamine conjunctival staining was seen at 14 and 28 days. This first-in-human study of Lacripep in patients with primary Sjögren syndrome demonstrated clinically significant improvements in specific signs and symptoms on which to base future studies. This study established safety and tolerability and potential metrics of efficacy in patients with moderate to severe disease. Further work on appropriate dosing and concentration is ongoing.
影响因子：
3.4
作者：
McKown, Robert L.;Wang, Ningning;Raab, Ronald W.;Karnati, Roy;Zhang, Yinghui;Williams, Patricia B.;Laurie, Gordon W.
通讯作者：
Laurie, Gordon W.
影响因子：
4.4
作者：
McNamara NA;Ge S;Lee SM;Enghauser AM;Kuehl L;Chen FY;Gallup M;McKown RL
通讯作者：
McKown RL