Tolerability, Safety and Efficacy of Lubricin (150 µg/ml) Eye Drops Versus Sodium Hyaluronate (HA) 0.18% Eye Drops in Patients With Moderate Dry Eye (DE)

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 an 2007 international dry eye workshop (DEWS) defined the disease as follows: Dry eye is a multifactorial disease of the tears and oc symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied 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, 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, pr lubricin is a principal lubricating protein in joints. Besides the lubricating property, lubricin has been shown to exert anti-adhesive ac 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 the protein with most potent lubricant and anti-adhesive properties present on the ocular surface and on meibomian gland. The presence on the ocular surface was first described by the team of Sullivan D. Based on the available preclinical studies lubricin 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. A clinical investigation is currently ongoing to demonstrate that a Lubricin 150 µg/ml eye drop formulation is non-inferior to an ocular surface lubricant sodium hyaluronate 0.13%. Up to now, there are no known anticipated adverse events associated with the use of lubricin, anyway the occurrence of side effect It must be considered that topical treatment with lubricin or hyaluronic acid could cause local irritation or allergic reactions. There ar contraindications to the use of lubricin or hyaluronic acid eye drops. All examinations and assessments that will be carried out durin invasive, are commonly used in the management of subjects with dry eye and pose no risk to the subjects. There are no known co 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. The objective of this study is to evaluate tolerability, safety and efficacy of Lubricin 150 µg/ml eye drops when compared to a widely used commercial 0.18% sodium hyaluronate eye drop formulation in moderate dry eye patients.

Official Title
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A 2 Week, Randomized, Double-masked, Controlled, Parallel Group and 1 Week Follow-up Study to Evaluate Tolerability, Safety and Efficacy of Lubricin (150 µg/ml) Eye Drops Versus Sodium Hyaluronate (HA) 0.18% Eye Drops in Patients With Moderate Dry Eye (DE)

Conditions
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Dry Eye Syndrome

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) within 7 days before study treatment and confirmed at baseline visit (V2): Patients 18 years of age or older. Patients 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) Patients diagnosed with dry eye from at least 3 months (current use or recommended use of artificial tears for the treatment of Dry Eye) Average VAS score for typical symptoms of Dry Eye (foreign body sensation, burning/stinging, itching, pain, stick feeling, blurred vision and photophobia) ≥ 25 mm; Corneal staining score with fluorescein > 3 using the Oxford corneal grading system in the worst performing eye; Schirmer test without anaesthesia ≤ 10 mm/5 minutes in the worst performing eye; Tear film break-up time (TBUT) ≤ 10 seconds in the worst performing eye Best corrected distance visual acuity (BCDVA) score ≥ 0.1 decimal units in both eyes at the time of study enrollment. Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent form signed by patients and/or legal representative must have been approved by the Ethics Committee for the current study. Exclusion Criteria: Patients with a mild Dry Eye condition (severity level 1 according to the Report of the International Dry Eye Workshop -DEWS, 2007) Patients with a severe Dry Eye condition (severity level 4 according to the Report of the International Dry Eye Workshop -DEWS, 2007) Best corrected distance visual acuity (BCDVA) score of < 0.1 decimal units in either eye at the time of study enrolment Evidence of an active ocular infection in either eye History or presence of ocular surface disorders not related to dry eye in either eye Use of any ocular topical medication other than the study medications for the treatment of ocular diseases including artificial tears during the study period 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 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 screening/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 an Intra Uterine Device 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 0.18% eye drops | Device: Sodium Hyaluronate<br>* Sodium hyaluronate 0.18% eye drops<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTAE (pre-treatment adverse events) | Pre-treatment Adverse Events | Screening | 
| Foreign body sensation (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Baseline (Day 1) | 
| Foreign body sensation (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Day 14 | 
| Burning/Stinging (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Baseline (Day 1) | 
| Burning/Stinging (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Day 14 | 
| Itching (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Baseline (Day 1) | 
| Itching (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Day 14 | 
| Pain (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Baseline (Day 1) | 
| Pain (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Day 14 | 
| Sticky feeling (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Baseline (Day 1) | 
| Sticky feeling (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Day 14 | 
| Blurred vision (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Baseline (Day 1) | 
| Blurred vision (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Day 14 | 
| Photophobia (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Baseline (Day 1) | 
| Photophobia (VAS for Local Ocular Tolerability) | VAS for Local Ocular Tolerability | Day 14 | 
| TEAE (treatment-emergent adverse events) | Treatment-emergent Adverse Events | Baseline (Day 1) | 
| TEAE (treatment-emergent adverse events) | Treatment-emergent Adverse Events | Day 7 | 
| TEAE (treatment-emergent adverse events) | Treatment-emergent Adverse Events | Day 14 | 
| TEAE (treatment-emergent adverse events) | Treatment-emergent Adverse Events | Follo-up (Day 21) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal fluorescein surface staining (Oxford score) | Corneal fluorescein surface staining (Oxford score) | Screening | 
| Corneal fluorescein surface staining (Oxford score) | Corneal fluorescein surface staining (Oxford score) | Baseline (Day 1) | 
| Corneal fluorescein surface staining (Oxford score) | Corneal fluorescein surface staining (Oxford score) | Day 14 | 
| TFBUT (Tear Film Break Up Time) | Tear Film Break Up Time | Screening | 
| TFBUT (Tear Film Break Up Time) | Tear Film Break Up Time | Baseline (Day 1) | 
| TFBUT (Tear Film Break Up Time) | Tear Film Break Up Time | Day 14 | 
| SANDE (Symptom Assessment in Dry Eye) | Symptom Assessment in Dry Eye | Screening | 
| SANDE (Symptom Assessment in Dry Eye) | Symptom Assessment in Dry Eye | Baseline (Day 1) | 
| SANDE (Symptom Assessment in Dry Eye) | Symptom Assessment in Dry Eye | Day 14 | 
| Schirmer Test I (without anaesthesia) | Schirmer's test I (without anaesthesia) | Screening | 
| Schirmer Test I (without anaesthesia) | Schirmer's test I (without anaesthesia) | Baseline (Day 1) | 
| Schirmer Test I (without anaesthesia) | Schirmer's test I (without anaesthesia) | Day 14 | 
| Best corrected distance visual acuity (ETDRS Score) | Best corrected distance visual acuity | Screening | 
| Best corrected distance visual acuity (ETDRS Score) | Best corrected distance visual acuity | Baseline (Day 1) | 
| Best corrected distance visual acuity (ETDRS Score) | Best corrected distance visual acuity | Day 14 | 

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