Cyclosporine A (0.05%) Ophthalmic Gel in the Treatment of Dry Eye Disease: A Multicenter, Randomized, Double-Masked, Phase III, COSMO Trial

Abstract

Wenyan Peng,1,* Xiuying Jiang,1,* Lei Zhu,2,* Xiaofeng Li,3,* Qizhi Zhou,4,* Ying Jie,5 Zhipeng You,6 Miaoqin Wu,7 Xiuming Jin,8 Xiaoyi Li,9 Shiyou Zhou1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of China; 2Henan Provincial People’s Hospital, Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450003, People’s Republic of China; 3Department of Ophthalmology, Chengdu Aier Eye Hospital, Sichuan, People’s Republic of China; 4Department of Ophthalmology, Chongqing Aier Eye Hospital, Chongqing, People’s Republic of China; 5Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 7Department of Ophthalmology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 8Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 9Zhaoke Ophthalmology Ltd, Guangzhou, 511458, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shiyou Zhou, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: To confirm the efficacy and safety of a novel ophthalmic cyclosporine A gel (CyclAGel, 0.05% CsA) in treating patients with moderate-to-severe dry eye disease (DED).Patients and Methods: The COSMO trial was a randomized, multicenter, double-masked, vehicle-controlled, phase III trial. Patients with moderate-to-severe DED were enrolled in 37 hospitals in China between November 2020 and April 2021. Eligible patients were randomized 1:1 to receive CyclAGel 0.05% or vehicle eye drops once nightly (QD). The primary endpoint was the proportion of subjects with at least a 1-point improvement in ICSS at day 84. Treatment-emergent adverse events (TEAEs) were recorded.Results: The full analysis set (FAS) included 315 and 312 participants in the CyclAGel and vehicle groups, respectively. The primary efficacy endpoint was achieved. The proportion of subjects with at least a 1-point improvement in ICSS from baseline to day 84 was significantly higher in the CyclAGel group than in the vehicle group (73.7% [232/315] vs 53.2% [166/312], P< 0.0001). Significant improvements relative to the vehicle were also observed in the ICSS and Oxford scale scoring of corneal and conjunctival fluorescein staining at day 14, 42, and 84. The Schirmer tear test results were significantly higher in the CyclAGel group than in the vehicle group on days 14 and 84 (all P< 0.05). The CyclAGel 0.05% was well tolerated, and the TEAEs were mostly mild. The most frequent treatment-related TEAE was eye pain (6.9% vs 1.6% in the CyclAGel and vehicle groups, respectively). No serious treatment-related TEAEs were reported.Conclusion: Clinically and statistically significant improvements in ICSS, tear production, and symptoms were observed in participants administered CyclAGel 0.05% QD for moderate-to-severe DED. CyclAGel 0.05% QD is a new effective, safe, and well-tolerated therapeutic option that might bring additional benefits of convenience and compliance as a once-A-day treatment for DED.Keywords: dry eye disease, cyclosporine, ophthalmic gel, corneal staining, dryness score

Keywords

• dry eye disease
• cyclosporine
• ophthalmic gel
• corneal staining
• dryness score