Study on Safety and Performance of an Artificial Tear in Dry Eye Treatment in Subjects With Ocular Surface Inflammation

Study Overview
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Brief Summary
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This is post-market study to evaluate the safety and efficacy of MDI - 101 a novel tear substitute for the treatment of dry eye (DE) in subjects with evidence of inflammation of the ocular surface. In particular, this study intends to evaluate, in a cohort of 25 patients, the anti-inflammatory properties of the product under study over a period of 10 weeks

Detailed Description
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DE is a common eye condition that affects 1 to 2 out of 10 persons in the world. Regardless of the underlying ethology, DE is associated with increased inflammation of conjunctiva, cornea and adnexa. As consequence of the recognized role of the inflammation in the etiopathogenesis of DE, direct and indirect anti-inflammatory treatments are currently the cornerstone for the management of DE, leading to the inhibition of the expression of inflammatory mediators on the ocular surface, therefore restoring the secretion of a healthy tear film and consequently reducing signs and symptoms of DE. MDI - 101, the product under study containing arabinogalactan (AG), trehalose and hyaluronic acid (HA) ,is a medical device with European Conformity (CE) mark that, thanks to the muco-adhesive proprieties of AG enriches the natural mucous of the tear film providing enhanced lubrication and protection and anti-inflammatory properties, in combination with trehalose and HA. The aim of this study is to demonstrate that the reduced ocular discomfort and the improvement of the integrity of the ocular surface are due to the interruption of the vicious cycle of inflammation. This open-label study involves a cohort of 24 patients with clinical and instrumental signs of inflammation of the ocular surface and includes end-points of efficacy, safety and evaluation of inflammation markers. The study includes 6 visits over 10 weeks, 8 of which of active treatment. This study is conducted during the Covid-19 pandemic and for this reason, clinical assessments of all the 24 patients are carried out remotely, from patients' home, with the adoption of digital solutions that determine: reduction of 66% of physical contacts between investigator and patient, a total of 90% of efficacy and safety data collected remotely and a reduction of 100% of physical contacts between investigator and clinical monitor, keeping the study entirely within the Good Clinical Practice framework.

Official Title
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Pilot Study on Safety and Performance of an Artificial Tear Containing Arabinogalactan, Trehalose and Hyaluronic Acid in the Treatment of Dry Eye in Subjects With Inflammation of the Ocular Surface

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Device: Artificial tear MDI - 101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who gave their written consent for participation in the study and for personal data processing and willing to comply with all study procedures. Males or females 30-75 years old. Subjects who are familiar with the needs of the study in the use of mobile devices and internet. Subjects who successfully completed the electronic registration for the clinical trial using their own study electronic Patient Reported Outcome (ePRO) profile and completed the OSDI questionnaire. Subjects who had been diagnosed as having dry eye symptoms for at least 3 months, fulfilling all the following four criteria: i. OSDI score of >18 evaluated by the questionnaire of Ocular Surface Disease Index (OSDI); ii. Non-invasive breakup time (NIBUT) ≤10 seconds at least in one eye; iii. Levels of MMP-9 in tears ≥ 40 ng/ml as assessed by the Inflammatory assay at least in one eye; iv. Cornea surface scores ≥1 and <4, based on Efron grading system. - Exclusion Criteria: Contact lens wearers. Subjects who did use any artificial tear for at least 7 days before baseline. Severe corneal damage (cornea surface scores ≥4, based on Efron grading system) or cornea surface normal (scores <1 based on Efron grading system) Corneal abrasions or other corneal abnormalities, blepharitis, meibomitis, lid abnormalities. Conjunctivitis of infective or allergic origins, ongoing or resolved less than 4 weeks before baseline visit. Subjects participating in another clinical study, on-going or completed less than 4 weeks before. Subject using, or will use during the study, other artificial tear or other ophthalmic products including, but not limited, to: corticosteroids, antibiotics, vasoconstrictor agents.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Interventional Model Description: Open label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDI - 101<br>Artificial tear containing arabinogalactan, trehalose and hyaluronic acid | Device: Artificial tear MDI - 101<br>* Medical device CE marked - artificial tears containing arabinogalactan, trehalose and hyaluronic acid - 10 weeks treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Ocular Surface Disease Index (OSDI) | Change of OSDI score versus baseline at any study time-point. The main goal of the study is to gather information about the efficacy, assessed by OSDI (Ocular Surface Disease Index) questionnaire, of artificial tear containing AG, trehalose and HA (MDI - 101) used in the treatment of symptoms of DE of various aetiology, with evidence of inflammation of the ocular surface. The OSDI score ranges from 0 (better outcome) to 100 (worst outcome) | 1 week - 2 weeks - 4 weeks - 6 weeks - 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Additional efficacy parameters: Matrix Metalloproteinase 9 (MMP-9) | Change of tear matrix metalloproteinase(MMP)-9 at T0 vs final assessment. The result of the MMP test could be NEGATIVE if the level of MMP-9 is < 40 ng/ml (better outcome) or POSITIVE if the level of MMP-9 is ≥ 40 ng/ml (worst outcome) | 8 weeks | 
| Additional Efficacy parameters: EFRON SCALE | Change of Efron Grading Scales at T0 vs final assessment. The Efron grading scale range from 0 (cornea surface normale) to 4 (severe corneal damage) | 8 weeks | 
| Additional Efficacy parameters: Corneal and Conjunctival Staining | Change of Corneal and Conjunctival Staining at T0 vs final assessment. The Staining scale ranges from 0 (better outcome) to 3 (worst outcome) | 8 weeks | 
| Additional Efficacy parameters: NIBUT | Change of NIBUT at T0 vs final assessment. The result of the Non-Invasive Break-Up Time (NIBUT) test could be >10 seconds (better outcome) or ≤10 seconds (worst outcome) | 8 weeks | 
| Additional Efficacy parameters: Osmolarity | Change of Osmolarity at T0 vs final assessment. The higher the tear film osmolarity, the greater the severity of the ocular surface damage. | 8 weeks | 
| Additional Efficacy parameters: Ocular Protection Index | Change of Ocular Protection Index (OPI) at T0 vs final assessment The principle of the test is that when BUT is shorter than the blink interval, the eyes are exposed to the risk of focal ocular surface damage. | 8 weeks | 
| Additional Efficacy parameters: meniscometry | Change of meniscometry at T0 vs final assessment. The lowest tear meniscus radius, the higher the severity of the ocular surface health | 8 weeks | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Safety Adverse Event (AE) experienced with the artificial tear assessed by the patient, before the ocular examination or reported by the patient at any time during the study. | 8 weeks | 
| Incidence of change in the unaided and corrected visual acuity | Unaided and corrected visual acuity Snellen test will be performed to evaluate change in the unaided and corrected visual acuity at T0 vs final assessment. | 8 weeks | 
| Incidence of change in the Intraocular pressure | Change of Intraocular pressure at T0 vs final assessment. | 8 weeks | 
| Evaluation of the Tolerability Signs and symptoms of discomfort | Treatment adherence assessed by the patient at any study time-point (number of instillations in the past 24 hours). | 8 weeks | 
| Treatment adherence (24 hours) | Treatment adherence assessed by the patient at any study time-point (number of instillations in the past 24 hours) | 8 weeks | 
| Treatment adherence (total days) | Treatment adherence assessed by the patient at any study time-point (number of days of product usage). | 8 weeks |