Tolerability, Safety and Efficacy of Lubricin Eye Drops vs Sodium Hyaluronate Eye Drops in Subjects With Mod. Dry Eye

Study Overview
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Brief Summary
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Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Lubricin is a mucin-like glycoprotein originally discovered in synovial fluid, as a secreted product of cells that line the joint tissues, which is present at the surface of articular cartilage and it has been investigated on its roles at the ocular surface, in normal and pathologic conditions such as dry eye. The objective of the study is to assess the tolerability, safety and efficacy of Lubricin eye drops solution administered over 4 weeks versus sodium hyaluronate (Na-HY) eye drops solution in subjects with moderate dry eye.

Detailed Description
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Dry eye, or keratoconjunctivitis sicca, is a chronic inflammatory condition of the ocular surface that may cause severe symptoms and visual impairment. The 2007 international dry eye workshop (DEWS) defined the disease as follows: Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Lubricin is a mucin-like glycoprotein originally discovered in synovial fluid, as a secreted product of cells that line the joint tissues, which is present at the surface of articular cartilage. In vitro studies have shown that lubricin in saline buffer acts as a lubricant between various surfaces, as well as in synovial fluid, providing evidence that lubricin is a principal lubricating protein in joints. Besides the lubricating property, lubricin has been shown to exert anti-adhesive action, strain energy dissipation, and a protective effect on underlying cells. Lubricin has been investigated on its roles at the ocular surface, in normal and pathologic conditions such as dry eye. In fact, Lubricin is a natural human protein with most potent lubricant and anti-adhesive properties present on the ocular surface and on meibonian gland. The presence of this protein at the ocular surface was first described by the team of Sullivan D. Based on the available preclinical lubricin studies may be an important barrier to the development of corneal and conjunctival epitheliopathies in dry eyes and its use as a novel lubricating and anti-adhesive eye drop is under investigation in this clinical investigation. This clinical investigation has been designed to demonstrate that a Lubricin 150 µg/ml eye drop formulation is non-inferior to the currently most-widely used ocular surface lubricant sodium hyaluronate 0.13% in improving signs and symptoms in patients with moderate dry eye. Up to now, there are no known anticipated adverse events associated with the use of lubricin, anyway the occurrence of side effects cannot be excluded. It must be considered that topical treatment with lubricin or hyaluronic acid could cause local irritation or allergic reactions. There are no known contraindications to the use of lubricin or hyaluronic acid eye drops. All examinations and assessments that will be carried out during this study are non-invasive, are commonly used in the management of subjects with dry eye and pose no risk to the subjects. There are no known contraindications to the use of lubricin or hyaluronic acid eye drops. No data are available about the embryo and fetal toxicity, therefore the experimental treatment will not be allowed to pregnant women or nursing mothers and women of childbearing potential not using appropriate birth control methods.

Official Title
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A Randomized, Double-masked, Controlled, Non-inferiority Study to Evaluate Tolerability, Safety and Efficacy of Lubricin Eye Drops vs Sodium Hyaluronate Eye Drops Given 4 Times a Day for 4 Weeks & 1 Week Follow-up in Subjects With Dry Eye

Conditions
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Dry Eye Syndrome, Tear Film Insufficiency

Intervention / Treatment
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* Device: Lubricin
* Device: Sodium Hyaluronate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be checked at the screening visit (V1) from day -14 to day -8 days before run-in period and confirmed at baseline visit (V2): Subjects 18 years of age or older. Subjects with moderate dry eye characterized by tear film osmolarity > 312 mOsm Subjects with both VAS for frequency and severity of symptoms, SANDE items, at screening & baseline > 25 mm (SANDE overall score > 25 mm). Subjects with moderate dry eye characterized by at least one eye with signs and symptoms of moderate dry eye (grade 2 or 3 of the 2007 DEWS report) Subjects diagnosed with dry eye from at least 6 months (current use or recommended use of artificial tears/lubricants for the treatment of Dry Eye) Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units in both eyes at the time of study enrolment. The Informed Consent by approved Ethics Committees should be signed by the subject before any study procedures. Exclusion Criteria: Evidence of an active ocular infection in either eye History or presence of ocular surface disorders not related to dry eye in either eye History or evidence of eyelid abnormality in either eye Use of topical cyclosporine, topical corticosteroids or any other topical medication for the treatment of dry eye in either eye within 30 days of study enrolment History of any ocular surgery (including laser or refractive surgical procedures) in either eye within the 90 days before study enrolment. Ocular surgery will not be allowed during the study treatment period and elective ocular surgery procedures should not be planned during the duration of the follow-up period Presence or history of any ocular or systemic disorder or condition that might significantly hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the investigator to be incompatible with the study visit schedule or conduct of trail procedures (e.g. ocular trauma, progressive or degenerative corneal conditions, uveitis, systemic vasculitis, collagen vascular diseases, poorly controlled diabetes, autoimmune disease, systemic infection.) Known hypersensitivity to one of the components of the study or procedural medications Participation in another clinical study at the same time as the present study or within 90 days of baseline visit History of drug, medication or alcohol abuse or addiction. Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions: are currently pregnant or, have a positive result on the urine pregnancy test at the Screening/Baseline Visit or, intend to become pregnant during the study treatment period or, are breast-feeding or, not willing to use highly effective birth control measures, such as: Hormonal contraceptives - oral, implanted, transdermal, or injected and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or IUD during the entire course of and 30 days after the study treatment periods.

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lubricin<br>Lubricin 150 µg/ml eye drops solution | Device: Lubricin<br>* Lubricin 150 µg/ml eye drops<br>|
| Active Comparator: Sodium Hyaluronate<br>Sodium hyaluronate 0.13% eye drops | Device: Sodium Hyaluronate<br>* Sodium hyaluronate 0.13% eye drops<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SANDE | SANDE Questionnaire - TOTAL SCORE | day 28±4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Total Tolerability Score | VAS | day 28±4 | 
| Oxford score | Corneal fluorescein surface staining | day 28±4 | 
| Tear Osmolarity | Tear osmolarity is an important indicator of the eye surface health. <300 mOsm/L: normal; 300 < mOsm/L< 320: mild instability of the tear film; 320 < mOsm/L< 340: moderate; <340: severe. | day 28±4 | 
| Schirmer-I Test | Schirmer's test I (without anaesthesia) | day 28±4 | 
| Tear Film Break Up Time | TFBUT | day 28±4 | 
| Best corrected distance visual | BCVA | day 28±4 | 
| Corneal fluorescein surface staining (Oxford score) | The Oxford score divides corneal staining into six groups according to severity from 0 (absent) to 5 (severe). The examiner compares the overall appearance of the patient's corneal staining with a reference figure, simulating the pattern of staining encountered in dry eye disease. | day 28±4 | 
| IOP | Intraocular pressure | day 28±4 | 
| TEAE | Adverse Events occurring after the first dose of Device | day 28±4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry Eye