ESSENCE 2: CyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (DED)

Study Overview
=================
Brief Summary
-----------------
The objective of this pivotal trial is to assess the efficacy, safety and tolerability of CyclASol in comparison to the vehicle for the treatment of signs and symptoms of Dry Eye Disease (DED).

Detailed Description
-----------------
This Phase 3 study will assess the efficacy, safety and tolerability of CyclASol 0.1% Ophthalmic Solution administered bilaterally twice daily versus vehicle.

Official Title
-----------------
A Phase 3, Multi-center, Randomized, Double-masked, Vehicle-controlled Clinical Trial to Assess the Efficacy and Safety of Topical CyclASol® for the Treatment of Dry Eye Disease

Conditions
-----------------
Dry Eye Disease

Intervention / Treatment
-----------------
* Drug: CyclASol topical ocular, eye drops
* Drug: Vehicle topical ocular, eye drops


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed ICF (Informed Consent Form) Patient-reported history of DED in both eyes Current use of OTC (over-the-counter) and/or artificial tears for dry eye symptoms Ability and willingness to follow instructions, including participation in all study assessments and visits Exclusion Criteria: Women who are pregnant, nursing or planning a pregnancy Unwillingness to submit a urine pregnancy test at screening and the last visit (or early termination visit) if of childbearing potential, or unwillingness to use acceptable means of birth control Clinically significant slit-lamp findings or abnormal lid anatomy at screening Ocular/periocular malignancy History of herpetic keratitis Active ocular allergies or ocular allergies that may become active during the study period Ongoing ocular or systemic infection at screening or baseline Wear of contact lenses within 3 months prior to screening or anticipated use of contact lenses during the study Use of topical Cyclosporine A or Liftigrast within 2 months prior to screening Intraocular surgery or ocular laser surgery within the previous 6 months, or have any planned ocular and/or lid surgeries over the study period Presence of uncontrolled systemic diseases Presence of known allergy and/or sensitivity to the study drug or its components Randomized in a previous CyclASol trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CyclASol Ophthalmic Solution<br>Cyclosporine A solution in vehicle | Drug: CyclASol topical ocular, eye drops<br>* Cyclosporine A solution in vehicle<br>* Other names: Ciclosporine (CSA);|
| Placebo Comparator: Vehicle Ophthalmic solution<br>Vehicle only | Drug: Vehicle topical ocular, eye drops<br>* Vehicle<br>* Other names: Vehicle;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Corneal Fluorescein Staining | Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst). | baseline and 1 month [day 29] | 
| Change From Baseline in Eye Dryness Score | Eye dryness score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort. | baseline and 1 month [day 29] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Conjunctival Lissamine Green Staining | Conjunctival staining was assessed by the investigator in the nasal and temporal sections. The Oxford Scheme was used for each section, with a possible score of 0-5 for each section, where 0=absent and 5=severe. The nasal and temporal scores were summed, for a possible score of 0-10 for each eye. | baseline and 1 month [day 29] | 
| Proportion of Responders in Central Corneal Fluorescein Staining Score | ≥ 1 score improvement for cCFS on National Eye Institute (NEI) scale: Central Corneal Fluorescein Staining (cCFS) is graded based on the NEI scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). | baseline and 1 month [day 29] | 
| Proportion of Responders in Total Corneal Fluorescein Staining Score | ≥ 3 scores improvement for tCFS on National Eye Insititute (NEI) scale: Total Corneal Fluorescein Staining (tCFS) is graded based on the NEI scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) -15 (worst). | baseline and 1 month [day 29] | 
| Change From Baseline in Central Corneal Fluorescein Staining | Central Corneal Fluorescein Staining (cCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). | baseline and 1 month [day 29] | 
| Change From Baseline in Total Corneal Fluorescein Staining | Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst). | baseline and 2 weeks [day 15] | 
| Change From Baseline in Visual Analogue Scale (VAS) for Blurred Vision | Blurred vision score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort. | baseline and 1 month [day 29] |