Wolstan & Goldberg Eye Associates, Torrance, California.
Ophthalmology Associates, Cornea and LaserVision Institute, St. Louis, Missouri.
Ophthalmology. 2019 Sep;126(9):1230-1237. doi: 10.1016/j.ophtha.2019.03.050. Epub 2019 Apr 6.
To evaluate the safety and efficacy of OTX-101, a novel aqueous nanomicellar formulation of cyclosporine (0.09%), in the treatment of patients with dry eye disease (DED).
A randomized, multicenter, vehicle-controlled, double-masked, phase 3 clinical trial.
Adults (18-90 years of age) with a history and clinical diagnosis of DED, a global symptom score of 40 or more (range, 0-100), and a lissamine green conjunctival staining score of 3 or more and 9 or less (range, 0-12) in at least 1 eye.
Eligible patients entered a run-in period of 14 to 20 days in which all patients administered vehicle twice daily. Patients who remained eligible at the baseline (day 0) visit were randomized in a 1:1 ratio to twice-daily treatment with OTX-101 0.09% or vehicle for 84 days.
Efficacy assessments included signs (unanesthetized Schirmer tear test, corneal and conjunctival staining) and symptoms (global symptom score) of DED. The primary end point was the proportion of eyes with a clinically meaningful improvement (increase of ≥10 mm) in Schirmer test score at day 84. Safety evaluations included adverse events (AEs), visual acuity, and intraocular pressure monitoring, slit-lamp, dilated ophthalmoscopy, and fundus examinations.
A total of 744 patients were randomized and received study medication (371 to OTX-101 0.09% and 373 to vehicle). The primary end point was achieved; a significantly greater percentage of eyes in the OTX-101 0.09% treatment group achieved an increase of 10 mm or more in the Schirmer test score at day 84 (OTX-101 0.09%, 16.6%; vehicle, 9.2%; P < 0.001). Significant improvements relative to vehicle also were observed for corneal (days 28, 56, and 84) and conjunctival (days 56 and 84) staining. The global symptom score was reduced from baseline in both treatment groups by approximately 30%; however, no significant separation between groups was observed. The OTX-101 0.09% formulation was well tolerated. Treatment-emergent AEs were primarily mild in intensity.
Clinically and statistically significant improvements in tear production and ocular surface integrity were observed in patients treated with OTX-101 0.09% for DED.
评估新型环孢素（0.09%）水包纳米胶束制剂 OTX-101 治疗干眼症（DED）患者的安全性和疗效。
一项随机、多中心、对照剂双盲、3 期临床试验。
有 DED 病史和临床诊断、全球症状评分≥40 分（0-100 分）、至少 1 只眼丽丝胺绿结膜染色评分≥3 分且≤9 分（0-12 分）的成年人（18-90 岁）。
符合条件的患者先进入为期 14-20 天的导入期，所有患者每天接受对照剂治疗 2 次。在基线（第 0 天）访视时仍符合条件的患者，按 1:1 的比例随机接受 OTX-101 0.09%或对照剂每日 2 次治疗，共 84 天。
疗效评估包括 DED 的体征（非麻醉性 Schirmer 泪液测试、角膜和结膜染色）和症状（全球症状评分）。主要终点是第 84 天 Schirmer 测试评分增加≥10mm 的眼比例。安全性评估包括不良事件（AE）、视力和眼压监测、裂隙灯、散瞳眼底检查和眼底检查。
共 744 例患者随机接受研究药物治疗（OTX-101 0.09%组 371 例，对照剂组 373 例）。主要终点达到；在 OTX-101 0.09%治疗组中，Schirmer 测试评分增加≥10mm 的眼比例显著高于对照剂组（OTX-101 0.09%组为 16.6%，对照剂组为 9.2%；P<0.001）。与对照剂相比，角膜（第 28、56 和 84 天）和结膜（第 56 和 84 天）染色也有显著改善。两组的全球症状评分均从基线下降约 30%；然而，两组之间没有显著分离。OTX-101 0.09%制剂的耐受性良好。治疗出现的 AE 主要为轻度。
接受 OTX-101 0.09%治疗的 DED 患者泪液产生和眼表面完整性有临床和统计学意义上的改善。
