Evaluation of the Efficacy and Safety of DM05 Versus Optive™ on the Treatment of Moderate to Severe Ocular Dryness

Study Overview
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Brief Summary
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This study is a multicentric, comparative, randomized, investigator-blinded, in parallel groups study to demonstrate the non-inferiority of DM05 in comparison with Optive™, 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 DM05 in comparison with OptiveTM, in terms of cornea and conjunctiva staining (Oxford score), on worse eye, between D0 and D35. Comparison of D35 versus D0 and D84 versus D0 for each product and comparison between products for the following parameters: Evolution of cornea and conjunctiva staining (Oxford score) on worse eye. Evolution of OSDI score (Ocular Surface Disease Index). 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 during 84 days for DM05 and OptiveTM. Selection visit: D-14 to D-7 Wash-out period: 1 to 2 weeks with preservative-free 0.9% NaCl at 3 drops per day (Hydrabak®): D0 : inclusion visit Follow-up visits: D35, D84

Official Title
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Evaluation of the Efficacy and Safety of DM05 Versus Optive™ on the Treatment of Moderate to Severe Ocular Dryness

Conditions
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Dry Eye

Intervention / Treatment
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* Device: DM05 eye drops
* Device: Optive™ 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 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 or 2 weeks before inclusion (at 3 drops per day). Diagnosis of moderate to severe ocular dryness defined by a score OSDI (Ocular Surface Disease Index) ≥18. Subject with at least one eye with: Global ocular staining (cornea and conjunctiva) ≥4 and ≤9 (Oxford scale from 0 to 15) AND one the following criteria: Schirmer test ≥ 3mm/5 min and ≤9mm/ 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 protocol, 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 sanitary establishment. Major subject who is under guardianship or who is not able to express his 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) Within the last 3 months prior to the inclusion, history of ocular trauma, infection or inflammation not related to dry eye syndrome. Within the last 12 months, history of ocular allergy or ocular herpes. Refractive or cataract surgery within the last 6 months. Any laser other than refractive surgery within the last 3 months. Any troubles of the ocular surface not related to dry eye syndrome. Ocular hypertension or glaucoma needing an hypotonic treatment Subject having used artificial tears in the 6 hours preceding the inclusion visit. Use during the month preceding the inclusion or during the study of: isotretinoïd, cyclosporine, tacrolimus, sirolimus, pimecrolimus, punctual plugs. Any not stabilized 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: 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 (DM05 or Optive®).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: the investigational device: DM05<br>DM05 eye drops, multidose sterile emulsion, will be administered in the DM05 Arm at one to two drops instilled in each eye from 4 to 6 times per day during 84 days | Device: DM05 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>|
| Active Comparator: The comparative device : Optive™<br>Optive™ eye drops, multidose sterile solution, will be administered in the Optive Arm at one to two drops instilled in each eye from 4 to 6 times per day during 84 days | Device: Optive™ 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 DM05 in comparison with OptiveTM, 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 by schirmer test, at day 35 | 35 days | 
| Volume tear fluid secretion as assessed by schirmer test | Mean change from Baseline ( D0) in Volume tear fluid secretion as assessed by schirmer test, at day 84 | 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 |