A Study of the Efficacy and Safety of Cyclosporin Ophthalmic Gel in Subjects With Moderate to Severe Dry Eye Disease

A Phase 3, Multicenter, Randomized, Double-blind, Vehicle-controlled Efficacy and Safety Study of Cyclosporin Ophthalmic Gel in Subjects With Moderate to Severe Dry Eye Disease

This study is a multicenter, randomized, double-blind, placebo-controlled, superiority design Phase III clinical trial. The primary objective is to evaluate the efficacy and safety of cyclosporine ophthalmic gel versus placebo in the treatment of moderate to severe dry eye for 84 days.

Study Overview

• Status: Recruiting
• Conditions: Moderate to Severe Dry Eye
• Intervention / Treatment: Drug: Cyclosporine ophthalmic gel; Drug: Cyclosporine ophthalmic gel vehicle

Detailed Description

A total of 360 subjects are planned to be enrolled in this study. This study is divided into two stages. The first stage (double-blind treatment period) is the main efficacy and safety evaluation stage, which lasts for 84 days. During this period, subjects are randomly assigned to receive the experimental drug or control drug in a 1:1 ratio, with the analysis of the first stage as the main analysis. After completing the 84th day visit, the subjects will enter the second stage (open treatment period). The second stage is a safety observation period of 84 days, during which all subjects use the experimental drug.

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zuguo Liu; Phone Number: 13696984489; Email: zuguoliu@xmu.edu.cn

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China
      • Recruiting
      • Xiamen Eye Center of Xiamen University
      • Principal Investigator: Zuguo Liu
      • Contact: Zuguo Liu; Phone Number: 13696984489; Email: zuguoliu@xmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. aged ≥ 18 years old, males or females.
2. Subjects complained of ocular dryness in both eyes for at least 6 months at Visit 1.
3. Eye dryness score(EDS)(evaluated on a 0-100 VAS score) ≥40 at Visit 1 and Visit 2.
4. Ocular Surface Disease Index (OSDI) score ≥13 at Visit 1 and Visit 2.
5. Total corneal fluorescein staining score (tCFS) ≥2 in either eye and ≥1 in at least one region at Visit 1 and Visit 2.
6. Schirmer I test (without anesthesia) ≤ 5 mm/5 min in either eye at Visit 1 and Visit 2.

7. Subjects with moderate and severe dry eye in both eyes at Visit 1 and Visit 2:

   1. Moderate: ≥1 quadrant and no more than 2 quadrants of corneal damage and/or ≥5 and <30 corneal fluorescein staining spots on slit lamp microscopy;
   2. Severe: ≥2 quadrants of corneal damage and/or ≥30 corneal fluorescence staining spots on slit lamp microscopy.

Exclusion Criteria:

1. Subjects with severe dry eye requiring surgical treatment.
2. Systemic use of retinoids within the 12 months prior to Visit 1.
3. Subjects who have had intraocular surgery within 12 months prior to Visit 1 or who require intraocular surgery during the study; or subjects who have had eyelid surgery within 6 months prior to Visit 1.
4. Subjects treated with permanent lacrimal duct embolization; or subjects treated with temporary lacrimal duct embolization within 6 months prior to Visit 1.
5. Subjects with dry eye correlated with operation；
6. Subjects who had worn corneal contact lens within 3 months prior to Visit 1.
7. Those who have used cyclosporine preparations ocularly or systemically within 1 month prior to visit 1.
8. Those who have used lifitegrast eye drops or tacrolimus eye drops ocularly within 1 month prior to visit 1.
9. Subjects with dry eye secondary to scarring (e.g., radiation exposure, ocular chemical burns, Stevens-Johnson syndrome, keloid pemphigoid, conjunctival scarring) or severe conjunctival cup cells destruction (e.g., vitamin A deficiency).
10. Those with significant eyelid margin inflammation or meibomian gland dysfunction that, in the opinion of the investigator, may affect the outcome of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; 1 drop each time, once every night at bedtime	Drug: Cyclosporine ophthalmic gel; Administer to eyes; Other Names: Cyclosporine
Placebo Comparator: Control group; 1 drop each time, once every night at bedtime	Drug: Cyclosporine ophthalmic gel vehicle; Administer to eyes; Other Names: Vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eye Dryness Score(EDS)	Mean change from baseline in EDS scores (evaluated on a 0-100 VAS score) on Day 84 (binocular)	84 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eye Dryness Score(EDS)	Mean change from baseline in EDS scores (evaluated on a 0-100 VAS score) on Day 14 and Day 42 (binocular)	14 days and 42 days
Total VAS score for dry eye symptoms	Mean change from baseline in total VAS score of dry eye symptoms (evaluated on a 0-100 VAS score) on Day 14, Day 42 and Day 84 (binocular)	14 days, 42 days and 84 days
Total corneal fluorescein staining score(tCFS)	The proportion of subjects with a total corneal fluorescein staining score (tCFS, modified NEI scale) of 0 on Day 14, Day 42, and Day 84 (study eye)	14 days, 42 days and 84 days
Schirmer test	The proportion of subjects with a change of ≥ 10mm from baseline in the Schirmer test (tear secretion test) on Day 14, Day 42, and Day 84 (study eye)	14 days, 42 days and 84 days
tear film break-up time(BUT)	Mean change from baseline in tear film break-up time (BUT) measurements on Day 14, Day 42, and Day 84 (study eye)	14 days, 42 days and 84 days

Collaborators and Investigators

• Sponsor: Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.
• Investigators: Principal Investigator: Zuguo Liu, Xiamen Eye Center of Xiamen University

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 3, 2025
• First Submitted That Met QC Criteria: January 3, 2025
• First Posted (Actual): January 9, 2025

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Corneal Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Anti-Infective Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Dermatologic Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: ZKO-CSP-CSA-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No