Assess the Safety and Efficacy of CsA Ophthalmic Gel in Subjects With Moderate to Severe Dry Eye Disease

Study Overview
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Brief Summary
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The purpose of this study is to explore the efficacy and safety of CsA ophthalmic gel in the treatment of moderate to severe dry eye disease .

Detailed Description
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A multicenter,randomized, double-blind, vehicle-controlled Study.Subjects will be randomly assigned to the experimental group and the control group,experimental group: CsA eye gel: 0.3 g: 0.15 mg, once daily;One drop into each eye when you use it.hypromellose eye drops:10ml：50mg,three times a day Control group: vehicle. One drop into the eye, once daily;One drop into each eye when you use it.hypromellose eye drops:10ml：50mg,three times a day

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

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: CsA Ophthalmic Gel
* Drug: Placebo
* Drug: Hypromellose Eye Drop


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1）18≤Age≤80, both male and female 2）According to the symptoms and signs and ophthalmologic examinations, the patients were diagnosed as moderate to severe dry eye EDS score is more than 40 points; BUT is less than 10 s; Schirmer test result is less than 10mm/5 min; ICSS≥2 points. 3）The ICSS score of baseline decreased by≤ 20% compared with that of screening period 4）Agree to participate in the study and voluntarily sign informed consent. Exclusion Criteria: Severe dry eye patients requiring surgical treatment Had inner eye surgery within 12 months prior to screening or required inner eye surgery during the study period;Eyelid surgery was performed within 6 months prior to screening Patients receiving permanent lacrimal insertion or patients receiving temporary lacrimal insertion within 6 months prior to screening; Operation-induced dry eye Glaucoma patients; Unwilling to avoid wearing contact lenses; Systemic inflammation or active eye infection and blepharitis; Patients with multiple episodes of viral keratitis Patients with ocular cicatricial pemphigoid, obvious conjunctival scar, ocular chemical burn and neurotrophic keratoconjunctivitis Patients with malignant tumors in the past 5 years, except the thoroughly cured basal cell carcinoma of skin, squamous cell carcinoma in situ of skin, and primordial cervical cancer; Perimenopausal women are taking hormone replacement therapy Patients who cannot stop using other eye drops and other ophthalmic preparations during the study period; Patients with severe cardiopulmonary diseases, uncontrolled hypertension and diabetes, etc. that affect the collection or compliance of study parameters; ALT and AST ≥ 2 times of the normal upper limit, and serum creatinine ≥ 1.5 times of the normal upper limit With a history of central nervous system disease or epilepsy, and/or a mental state that does not cooperate Pregnant women and lactating women, or women of childbearing age, do not adopt effective contraceptive measures; Participated in other clinical trials or participated in other clinical trials within 1 months before the election; Systemic or topical cyclosporine drugs within 1 months before the election; Allergy to CsA, fluorescein or any component of the drug is known； Patients who were not considered suitable for the study, including those who were unable or unwilling to comply with the protocol requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>322 subjects will be treated with CsA eye gel: 0.3 g: 0.15 mg, 1 times daily, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks. | Drug: CsA Ophthalmic Gel<br>* The CsA eye gel of 0.3 g: 0.15 mg<br>* Other names: CsA gel;Drug: Hypromellose Eye Drop<br>* Hypromellose Eye Drops of 10ml：50mg, 3 times daily, 1-2 drop<br>* Other names: zhenshishuang;|
| Placebo Comparator: Control group<br>322 subjects will be treated with Placebo : 0 g: 0mg, 1 times daily, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks. | Drug: Placebo<br>* Placebo<br>Drug: Hypromellose Eye Drop<br>* Hypromellose Eye Drops of 10ml：50mg, 3 times daily, 1-2 drop<br>* Other names: zhenshishuang;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients whose corneal fluorescein staining score (ICSS) decreased by ≥1 point from baseline at visit 5 (study eye) | ICSS：no staining = 0，few/rare punctate lesions = 1，discrete and countable lesions = 2，lesions too numerous to count，but not coalescent = 3，coalescent = 4 | 84 days after admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EDS score at the NO.3, NO.4 and NO.5 visit was compared with the baseline EDS score (binocular) | 0-100 points VAS score was evaluated | 14 days after admission ，42 days after admission ，84days days after admission | 
| Average changes in VAS scores of 6 dry eye symptoms (burning/needling sensation, pruritus, foreign body sensation, discomfort, photophobia and pain) at the NO.3, NO.4 and NO.5 visit were compared with baseline (binocular) | 0-100 points VAS score was evaluated | 14 days after admission ，42 days after admission ，84days days after admission | 
| corneal fluorescein staining score (ICSS)at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular) | ICSS：no staining = 0，few/rare punctate lesions = 1，discrete and countable lesions = 2，lesions too numerous to count，but not coalescent = 3，coalescent = 4 | 14 days after admission ，42 days after admission ，84days days after admission | 
| oxford score at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular) | 0 V grade was evaluated | 14 days after admission ，42 days after admission ，84days days after admission | 
| Tear break-up time(BUT) at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular) | The time taken for the first dry spot to appear on the cornea after a complete blink with fluorescein | 14 days after admission，42 days after admission ，84days days after admission | 
| Schirmer's II test (with anesthetic) at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular) | Basal tear secretion with topical anesthesia, determined by the moisture length on the filter paper in 5 minutes | 14 days after admission ，42 days after admission ，84days days after admission |