Efficacy, Safety, and Tolerability of a Novel Cyclosporine, a Formulation for Dry Eye Disease: A Multicenter Phase II Clinical Study

• Published in: Clinical therapeutics Vol. 43; no. 3; pp. 613 - 628
• Main Authors: Peng, Wen-yan, Chen, Rong-xin, Dai, Hong, Zhu, Lei, Li, Ying, Gao, Zi-qing, Li, Xiao-yi, Zhou, Shi-you
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2021; Elsevier Limited
• Subjects: Adverse events; Burning; Chronic fatigue syndrome; Clinical trials; Cornea; cyclosporine; Cyclosporins; Dosage; Drug dosages; dry eye disease; efficacy; Eye diseases; Fluorescein; Immunomodulators; Internal Medicine; multicenter Phase II clinical study; Patients; Pruritus; Safety; Statistical analysis; Surgery; tolerability; United States > US; China; cyclosporine; dry eye disease; multicenter Phase II clinical study; safety; efficacy; tolerability
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2020.12.023

The purpose of this study was to explore the efficacy, safety, and tolerability of a novel cyclosporine formulation for dry eye disease (DED). This is an exploratory, multicenter, single-blind, randomized, positive-controlled Phase II clinical trial between cyclosporine ophthalmic gel (CyclAGel) and an open-label comparator (Restasis, positive control). A total of 240 eligible patients with moderate to severe DED were randomized to 4 study groups: CyclAGel 0.05%/once daily (QD) (n = 59), CyclAGel 0.05%/BID (n = 60), CyclAGel 0.1%/QD (n = 60), and Restasis 0.05%/BID (n = 61). After receiving BID dosing of hypromellose eye drops during a 2-week run-in period, patients were randomized to the respective treatment group and dosed QD or BID for 12 weeks. Efficacy was assessed based on a number of sign and symptom end points, including eye dryness score (visual analog scale), 6 other parameters of symptoms for dryness (burning/stinging, itching, foreign body sensation, discomfort, sensitivity to light, and pain), and corneal fluorescein staining. The Schirmer test was used to assess dry eye symptoms (visual analog scale severity) at visit 3 (week 2), visit 4 (week 6), and visit 5 (week 12). CyclAGel showed a consistent improvement in eye dryness score and the 6 other parameters of symptoms for dryness, corneal fluorescein staining, breakup time, and Schirmer test scores compared with Restasis over the 12-week treatment period. However, there were no statistically significant differences between CyclAGel and Restasis after baseline corrections were made, and the results of the full analysis set remained consistent with those of the per-protocol set (P > 0.05). Moreover, each CyclAGel-treated group (0.05%/QD, 0.05%/BID, and 0.1%/QD) exerted better effects than the Restasis group, and CyclAGel 0.05%/QD showed the most significant improvement. The number of ocular-related treatment-emergent adverse events was low in all treatment groups, with no serious drug-related treatment-emergent adverse events. CyclAGel showed excellent safety, tolerability, and comfort profiles at 2 concentrations and frequency in moderate to severe DED. [Display omitted] •Dry eye disease (DED) is a most common chronic disease.•The pathogenesis of DED is contributed to multiple factors.•CyclAGel (0.05%/qd) will be selected as the drug of clinical phase III trial study to further expand the sample size and verify the effectivity and safety in the treatment of the patients with moderate to severe dry eye disease.