A Study to Evaluate the Performance and Safety of Artelac Rebalance® Versus Vismed in the Management of Dry Eye

Study Overview
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Brief Summary
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The objective of this investigation is to show that the performance of Artelac Rebalance eye drops is non-inferior to that of Vismed eye drops in subjects with moderate to severe dry eye, and to assess the safety of Artelac Rebalance after a 90-day (± 10 day) treatment administered 3 to 5 times per day.

Detailed Description
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Artelac Rebalance and Vismed are in compliance with European Directives (CE marked) products in the European Union (EU).

Official Title
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A Study to Evaluate the Performance and Safety of Artelac Rebalance® Versus Vismed in the Management of Dry Eye

Conditions
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Dry Eye

Intervention / Treatment
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* Device: Artelac Rebalance
* Device: Vismed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have been using tear substitutes for at least 3 months prior to inclusion, and who will use preservative-free ART (Artelac® UNO CL hypromellose 0.32% w/v eye drops, single dose unit) up to 6 times a day for at least 2 weeks immediately prior to randomization Subjects with at least 1 eye with the following signs of keratoconjunctivitis sicca at 2 consecutive visits (Visit 1[Screening] and Visit 2 [Randomization]) Schirmer test without anesthesia of ≤ 9 mm/5min Tear break-up time of ≤ 10sec (mean of 3 measurements) Total ocular surface staining score ≥ 4 and ≤ 9. This assessment combines corneal fluorescein staining and nasal and temporal bulbar conjunctival lissamine green staining, each graded 0-5 according to the Oxford Scheme Subjects who have a decimal visual acuity (VA) with habitual correction equal to or better than 0.1 (Snellen E chart) in both eyes Subjects who are receiving stable systemic treatment (unchanged for 1 month or longer) Exclusion Criteria: Subjects with moderate or severe blepharitis Subjects who have severe ocular dryness accompanied by 1 of the following: Lid abnormality (except mild blepharitis) Corneal disease Ocular surface metaplasia Filamentary keratitis Corneal neovascularization Subjects who currently wear contact lenses or have worn contact lenses within 90 days prior to study start Subjects who have received ocular surgery, including laser surgery, in either eye within 180 days prior to study start Subjects with a history of ocular trauma, non-dry eye ocular inflammation, or ocular infection within 90 days prior to study start Subjects with a history of ocular allergic disease or ocular herpes within 1 year prior to study start Subjects with a history of any inflammatory ulcerative keratitis, recurrent corneal erosion, or uveitis Subjects with known hypersensitivity or contraindications to any of the ingredients in the test or comparator products Subjects with planned initiation of, or changes to, concomitant medication that could affect dry eye within 30 days of Visit 1 (Screening) or during the study Subjects who have received ocular therapy (either eye) with any ophthalmic medication, except tear substitutes, within 2 weeks prior to study start Subjects expected to receive ocular therapy during the study Subjects treated with topical ocular steroidal or non-steroidal anti- inflammatory medication within 30 days prior to study start Subjects expected to receive ocular therapy with immunosuppressants (eg, cyclosporine) during the study or who have used ocular immunosuppressants within 90 days prior to study start Subjects who have received occlusion therapy with lacrimal or punctum plugs within 90 days prior to study start

Ages Eligible for Study
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Minimum Age: 18 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artelac Rebalance<br>Artelac Rebalance ophthalmic solution contains 0.15% hyaluronic acid, is unpreserved and presented in single dose units with a fill volume of 0.5 mL. | Device: Artelac Rebalance<br>* Instill 1 drop of the Artelac Rebalance eye drops in each eye 3 to 5 times per day for 90(± 10) day treatment.<br>|
| Active Comparator: Vismed<br>Vismed ophthalmic solution, contains 0.18% sodium hyaluronate, is unpreserved and presented in single dose units with a fill volume of 0.3 mL. | Device: Vismed<br>* Instill 1 drop of the Vismed eye drops in each eye 3 to 5 times per day for 90(± 10) day treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Ocular Surface Staining Score | Total combined ocular surface staining grade of 0-15 combining corneal fluorescein staining score, nasal and temporal bulbar conjunctiva lissamine green staining score (each graded 0-5 on the Oxford Scheme) in the study eye. | Mean change from baseline (CFB) to visit 4 (day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Ocular Surface Staining Score | Mean CFB in the study eye at Visits 3, 4 and 5 in total combined ocular surface staining score. | Mean CFB to visit 3 (Day 7) visit 4 (Day 28) and visit 5 (Day 90) | 
| Corneal Fluorescein Staining Score | Mean CFB in the study eye in corneal fluorescein staining score at each follow-up visit | Mean CFB at each follow-up visit: visit 3 (Day 7) visit 4 (Day 28) and visit 5 (Day 90) | 
| Nasal Conjunctival Lissamine Green Staining | Mean CFB in the study eye in nasal conjunctival lissamine green staining at each follow-up visit. | Mean CFB at each follow-up visit: visit 3 (Day 7) visit 4 (Day 28) and visit 5 (Day 90) | 
| Temporal Conjunctival Lissamine Green Staining | Mean CFB in the study eye in temporal conjunctival lissamine green staining at each follow-up visit | Mean CFB at each follow-up visit: visit 3 (Day 7) visit 4 (Day 28) and visit 5 (Day 90) | 
| Tear Film Break-up Time | Mean CFB in the study eye in tear film break-up time (TFBUT) at each follow-up visit. | Mean CFB at each follow-up visit: visit 3 (Day 7) visit 4 (Day 28) and visit 5 (Day 90) | 
| Study Drop Sensation | Study drop sensation, as reported by subject in subject diary | Each follow-up visit: visit 3 (Day 7) visit 4 (Day 28) and visit 5 (Day 90) |