OC-01（伐尼克兰溶液）鼻喷雾剂治疗干眼病体征和症状的疗效与安全性：ONSET-2 3期随机试验
Efficacy and Safety of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease: The ONSET-2 Phase 3 Randomized Trial.
作者信息
Wirta David, Vollmer Patrick, Paauw James, Chiu Kuei-Hsun, Henry Eugenia, Striffler Kristen, Nau Jeffrey
机构信息
Eye Research Foundation, Newport Beach, California.
Vita Eye Clinic, Shelby, North Carolina.
出版信息
Ophthalmology. 2022 Apr;129(4):379-387. doi: 10.1016/j.ophtha.2021.11.004. Epub 2021 Nov 10.
PURPOSE
To evaluate the efficacy and safety of OC-01 (varenicline solution) nasal spray for treatment of patients with dry eye disease.
DESIGN
Randomized, multicenter, double-masked, vehicle-controlled, phase 3 study.
PARTICIPANTS
Adults 22 years of age or older with a diagnosis of dry eye disease, artificial tear use, Ocular Surface Disease Index score of 23 or more, and Schirmer test score (STS) of 10 mm or less. Eligibility was not restricted by eye dryness score (EDS).
METHODS
Patients (N = 758) were randomized in a 1:1:1 ratio to twice-daily treatment with 50-μl intranasal spray in each nostril of OC-01 0.03 mg (n = 260), OC-01 0.06 mg (n = 246), or vehicle (control; n = 252) for 4 weeks (ClinicalTrials.gov identifier, NCT04036292).
MAIN OUTCOME MEASURES
The primary efficacy end point was the percentage of patients achieving a 10-mm improvement or more in STS at week 4. Secondary end points included change from baseline to week 4 in STS and EDS in a controlled adverse environment (CAE) chamber and in the clinic. Treatment-emergent adverse events (TEAEs) were assessed.
RESULTS
A statistically significantly greater percentage of patients achieved the primary end point in both OC-01 treatment groups compared with the vehicle group (OC-01 0.03 mg, 47.3%; OC-01 0.06 mg, 49.2%; vehicle, 27.8%; P < 0.0001 for both doses). Change from baseline in STS at week 4 was statistically significantly greater for patients receiving OC-01 than vehicle (P < 0.0001 for both doses). Eye dryness score assessed at week 4 improved with OC-01 treatment compared with vehicle, although the difference was not significant for EDS measured in the CAE chamber and showed (nominal) significance in the clinic. Overall, 86.5% of patients (654/756) reported at least 1 TEAE during the treatment period; most were mild, nonocular (sneezing, cough, throat irritation, and instillation site irritation) and were reported by fewer patients in the vehicle group than in the OC-01 treatment groups (OC-01 0.03 mg, 97.3%; OC-01 0.06 mg, 99.2%; vehicle, 57%).
CONCLUSIONS
OC-01 nasal spray was well tolerated and showed a clinically meaningful effect on signs and symptoms of dry eye disease.
目的
评估OC - 01（伐尼克兰溶液）鼻喷雾剂治疗干眼症患者的疗效和安全性。
设计
随机、多中心、双盲、赋形剂对照的3期研究。
参与者
年龄在22岁及以上，被诊断为干眼症，使用人工泪液，眼表疾病指数评分23分及以上，且泪液分泌试验评分（STS）为10毫米或更低的成年人。入选不受干眼评分（EDS）限制。
方法
患者（N = 758）按1:1:1比例随机分为三组，每组每天两次，分别在每个鼻孔内使用50微升的OC - 01 0.03毫克（n = 260）、OC - 01 0.06毫克（n = 246）或赋形剂（对照组；n = 252）进行治疗，为期4周（ClinicalTrials.gov标识符，NCT04036292）。
主要观察指标
主要疗效终点是在第4周时STS改善10毫米或更多的患者百分比。次要终点包括在可控不良环境（CAE）舱和诊所中从基线到第4周的STS和EDS变化。评估治疗中出现的不良事件（TEAE）。
结果
与赋形剂组相比，两个OC - 01治疗组中达到主要终点的患者百分比在统计学上显著更高（OC - 01 0.03毫克组为47.3%；OC - 01 0.06毫克组为49.2%；赋形剂组为27.8%；两种剂量的P值均<0.0001）。接受OC - 01治疗的患者在第4周时STS相对于基线的变化在统计学上显著大于赋形剂组（两种剂量的P值均<0.0001）。与赋形剂相比，OC - 01治疗在第4周时评估的干眼评分有所改善，尽管在CAE舱中测量的EDS差异不显著，而在诊所中显示（名义上）有显著性差异。总体而言，86.5%的患者（654/756）在治疗期间报告了至少1次TEAE；大多数为轻度、非眼部（打喷嚏、咳嗽、喉咙刺激和滴注部位刺激），赋形剂组报告这些症状的患者比OC - 01治疗组少（OC - 01 0.03毫克组为97.3%；OC - 01 0.06毫克组为99.2%；赋形剂组为57%）。
结论
OC - 01鼻喷雾剂耐受性良好，对干眼症的体征和症状显示出具有临床意义的效果。
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