Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial

Lei Tian; Xiuming Jin; Jibing Wang; Yonggen Xu; Chengwei Lu; Shaozhen Zhao; Qian Zhu; Hong Dai; Hao Gu; Mingchang Zhang; Linnong Wang; Xiaohe Lu; Lixiao Ma; Lei Zhu; Qingyan Zeng; Hong Zhang; Yao Fu; Suxia Li; Liming Tao; Qian Ren; Faming Ding; Shenglin Zhang; Shaopin Zhu; Zhiping Li; Ying Jie

doi:10.1016/j.lanwpc.2024.101032

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial

Lancet Reg Health West Pac. 2024 Feb 27:45:101032. doi: 10.1016/j.lanwpc.2024.101032. eCollection 2024 Apr.

Authors

Lei Tian¹, Xiuming Jin², Jibing Wang³, Yonggen Xu⁴, Chengwei Lu⁵, Shaozhen Zhao⁶, Qian Zhu⁷, Hong Dai⁸, Hao Gu⁹, Mingchang Zhang¹⁰, Linnong Wang¹¹, Xiaohe Lu¹², Lixiao Ma¹³, Lei Zhu¹⁴, Qingyan Zeng¹⁵, Hong Zhang¹⁶, Yao Fu¹⁷, Suxia Li¹⁸, Liming Tao¹⁹, Qian Ren²⁰, Faming Ding²¹, Shenglin Zhang²¹, Shaopin Zhu²¹, Zhiping Li²¹, Ying Jie¹

Affiliations

¹ Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.
² Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
³ Department of Ophthalmology, Weifang Eye Hospital, Shandong, China.
⁴ Department of Ophthalmology, Peking University Third Hospital, Beijing, China.
⁵ Department of Ophthalmology, Bethune First Hospital of Jilin University, Changchun, China.
⁶ Department of Ophthalmology, Tianjin Medical University Eye Hospital, Tianjin, China.
⁷ Department of Ophthalmology, Tongji Hospital of Tongji University, Shanghai, China.
⁸ Department of Ophthalmology, Beijing Hospital, Beijing, China.
⁹ Department of Ophthalmology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
¹⁰ Department of Ophthalmology, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Hubei, China.
¹¹ Department of Ophthalmology, Nanjing First Hospital, Nanjing, China.
¹² Department of Ophthalmology, Zhujiang Hospital of Southern Medical University, Guangdong, China.
¹³ Department of Corneal, Hebei Eye Hospital, Xing Tai, China.
¹⁴ Department of Ophthalmology, Henan Eye Hospital, Henan Provincial People's Hospital, Zhengzhou, China.
¹⁵ Department of Ophthalmology, Wuhan Aier Eye Hospital Hankou Hospital, Hubei, China.
¹⁶ Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
¹⁷ Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁸ Department of Ophthalmology, Eye Hospital of Shandong First Medical University, Shandong, China.
¹⁹ Department of Ophthalmology, The Second Hospital of Anhui Medical University, Anhui, China.
²⁰ Department of Ophthalmology, Shijiazhuang People's Hospital, Hebei, China.
²¹ Jixing Pharmaceutical Co Ltd., Shanghai, China.

Abstract

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease.

Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4.

Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred.

Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population.

Funding: Jixing Pharmaceutical Co. Ltd.

Keywords: Dry eye disease; Eye dryness score; Nicotinic acetylcholine receptor agonist; Randomized clinical trial; Schirmer's test score; Varenicline nasal spray.