Evaluation of Efficacy and Safety of Vismed Gel Multi 0.3% Versus Vismed Multi 0.18% on Treatment of Ocular Dryness

Study Overview
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Brief Summary
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This study is a multicentric, comparative, randomized, investigator-blinded, parallel group study to demonstrate the non-inferiority of Vismed® Gel Multi 0.3% in comparison with Vismed® Multi 0.18% in terms of cornea and conjunctiva staining (Oxford score) on patients with moderate to severe ocular dryness, after 35 days of treatment.

Detailed Description
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Evaluation of the non-inferiority of Vismed® Gel Multi 0.3% in comparison with Vismed® Multi 0.18%, in terms of cornea and conjunctiva staining (Oxford score), on worse eye, between Day 0 and Day 35. Evaluation of the non-inferiority of Vismed® Gel Multi 0.3% in comparison with Vismed® Multi 0.18%, in terms of cornea and conjunctiva staining (Oxford score), on worse eye, between Day 0 and Day 35. Comparison of Day 35 versus Day 0 and Day 84 versus Day 0 for each product and comparison between products for the following parameters: Evolution of cornea and conjunctiva staining (Oxford score) on worse eye. Evolution of DEQ-5 score (5-items Dry Eye Questionnaire). Evolution of Van Bijsterveld score (Lissamine green staining) in worse eye. Evolution of Schirmer test result in worse eye. Evolution of Tear film Break-Up Time (TBUT) in worse eye. Evolution of ocular dryness severity by evaluation of each main symptom by the patient and total score of all symptoms Evaluation of treatment performance by the investigator and the patient. Evaluation of the average frequency of use over 84 days for both products.

Official Title
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Evaluation of the Efficacy and Safety of Vismed® Gel Multi 0.3% Versus Vismed® Multi 0.18% on the Treatment of Moderate to Severe Ocular Dryness

Conditions
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Dry Eye

Intervention / Treatment
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* Device: Vismed gel Multi 0.3% eye drops
* Device: Vismed Multi 0.18% eye drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sex: male or female. Age: more than 18 years. Subject with a moderate to severe dry eye syndrome needing artificial tears in the 3 months preceding the inclusion. Subject having used only artificial tears without preservative (NaCl 0.9%, Hydrabak®) during 1 to 2 weeks before inclusion (up to 6 times a day). Subject with a score ≥ 6 for the 5-Item Dry Eye Questionnaire (DEQ-5) Subject with at least one eye with: Global ocular staining (cornea and conjunctiva) ≥4 and ≤9 on the Oxford scale (0 to 15) AND one of the following criteria: Schirmer test ≥ 3 mm/5 min and ≤ 9 mm/5 min OR Sum of 3 measurements of Tear film Break-Up Time (TBUT) ≤ 30s. Subject, having given freely and expressly his/her informed consent. Subject who is able to comply with the study requirements, as defined in the present CIP, at the Investigator's appreciation. In France: subject being affiliated to a health social security system. Female subjects of childbearing potential should use a medically accepted contraceptive regimen since at least 12 weeks before the beginning of the study, during all the study and at least 1 month after the study end. Exclusion Criteria: Pregnant or nursing woman or planning a pregnancy during the study. Subject deprived of freedom by administrative or legal decision. Subject in a social or health institution Subject who is under guardianship or who is not able to express his/her consent. Subject being in an exclusion period for a previous study. Subject suspected to be non-compliant according to the Investigator's judgment. Subject wearing contact lenses during the study. Far best corrected visual acuity < 1/10 Subject with severe ocular dryness with one of these conditions: Eyelid or blinking malfunction Corneal disorders not related to dry eye syndrome Ocular metaplasia Filamentous keratitis Corneal neovascularization Subject with severe meibomian gland dysfunction (MGD) History of ocular trauma, infection or inflammation, not related to dry eye syndrome within the last 3 months prior to the inclusion. History of ocular allergy or ocular herpes within the last 12 months. Subjects who underwent ocular surgery, including laser surgery, in either eye within the last 6 months. Any troubles of the ocular surface not related to dry eye syndrome. Subject having used artificial tears in the 6 hours preceding the inclusion visit. Use of the following ocular treatments: isotretinoïd, cyclosporine, tacrolimus, sirolimus, pimecrolimus, punctual plugs during the month preceding the inclusion. Subjects who have received ocular therapy (either eye) with any ophthalmic medication, except tear substitutes, within 2 weeks prior to study start or expected to receive ocular therapy during the study. Any not stabilised systemic treatment, which can have an effect on performance or safety criteria, at the investigator appreciation.

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment Because the comparator will be in commercial packaging, the blinding of the subject is not possible. However, the study will be blinded for the investigator: evaluations will be done by an independent investigator, different than the person who will distribute the product. Subjects will be identified by a patient number. Each patient number will be associated to a treatment number, according to a randomization list provided before the beginning of the clinical investigation, and randomized either in one of both treatment groups (Vismed Gel Multi 3% or Vismed Multi 0.18%).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investig. device:Vismed Gel Multi 0.3%<br>Vismed gel Multi 0.3% eye drops: 1 to 2 drops in each eye between 4 and 6 times per day during 84 days | Device: Vismed gel Multi 0.3% eye drops<br>* Ophthalmic use. Vismed gel Multi 0.3% eye drops. One to two drops instilled in each eye from 4 to 6 times per day during 84 days of treatment.<br>|
| Active Comparator: Comparative device: Vismed Multi 0.18%<br>Vismed Multi 0.18% eye drops: 1 to 2 drops in each eye between 4 and 6 times per day during 84 days | Device: Vismed Multi 0.18% eye drops<br>* Ophthalmic use. One to two drops instilled in each eye from 4 to 6 times per day during 84 days of treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate the non-inferiority of Vismed® Gel Multi 0.3% in comparison with Vismed® Multi 0.18% in terms of cornea and conjunctiva staining (Oxford score) on patients with moderate to severe ocular dryness, after 35 days of treatment. | Assess the ocular surface fluorescein staining score- mean change from Baseline in the study at D35 in ocular surface fluorescein stainig score according to a scale from zero to 15 | 35 days | 
| To assess the total ocular surface fluorescein staining score at D84 | Mean change from Baseline (D0) in the study eye and D84 in the total ocular surface fluoresceine staining score | 0 and 84 days | 
| Evolution of DEQ-5 score | Evolution from Baseline of DEQ-5 questionnaire scores at day 35 | 35 days | 
| Evolution of DEQ-5 score | Evolution from Baseline of DEQ-5 questionnaire scores at day 84 | 84 days | 
| Evolution of Van Bijterveld score ( lissamine green staining) | Mean change from Baseline ( D0) and D 35 in the total Van Bijterveld score | 35 Days | 
| Evolution of Van Bijterveld score ( lissamine green staining) | Mean change from Baseline ( D0) and D 84 in the total Van Bijterveld score | 84 days | 
| Volume tear fluid secretion as assessed by schirmer test | Mean change from Baseline ( D0) in Volume tear fluid secretion as assessed | 35 days | 
| Volume tear fluid secretion as assessed by schirmer test | Mean change from Baseline ( D0) in Volume tear fluid secretion as assessed | 84 days | 
| Evolution of Tear film Break-Up Time | Mean change from Baseline (D0) in the study eye in TFBUT at Day 35 | 35 days | 
| Evolution of Tear film Break-Up Time | Mean change from Baseline (D0) in the study eye in TFBUT at Day 84 | 84 days | 
| Global sum score of dry eye symptoms at visit 3 - mean change from Baseline at visit 3 ( D35) | Mean change from Baseline in the global sum score of dry eye symptoms at D35 : discomfort,burning, stinging,eye dryness sensation, itching,foreign body sensation,photophobia, blurred vision.Each graded from 0 to 10 | 35 days | 
| Global sum score of dry eye symptoms at visit 4 - mean change from Baseline at visit 3 ( D84) | Mean change from Baseline in the global sum score of dry eye symptoms at D84 : discomfort,burning, stinging,eye dryness sensation, itching,foreign body sensation,photophobia, blurred vision.Each graded from 0 to 10 | 84 days | 
| Global treatment performance score assessed by the investigator at visit 3 | Total Treatment performance score graded from 0 to 4 | 35 days | 
| Global treatment performance score assessed by the investigator at visit 4 | Total Treatment performance score graded from 0 to 4 | 84 days | 
| Global treatment performance score assessed by the patient at visit 3 | Total Treatment performance score graded from 0 to 4 | 35 days | 
| Global treatment performance score assessed by the patient at visit 4 | Total Treatment performance score graded from 0 to 4 | 84 days |