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

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

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.

Study Overview

• Status: Completed
• Conditions: Dry Eye Syndrome; Tear Film Insufficiency
• Intervention / Treatment: Device: Lubricin; Device: Sodium Hyaluronate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Catania, Italy, 95123
    • Azienda OspedalieroUniversitaria "Policlinico Vittorio Emanuele" Presidio Ospedaliero, Gaspare Rodolico Clinica Oculistica
  • Messina, Italy, 98125
    • Centro Eccellenza Regionale Malattie della Superficie Oculare - Università di Messina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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):

1. Subjects 18 years of age or older.
2. Subjects with moderate dry eye characterized by tear film osmolarity > 312 mOsm
3. Subjects with both VAS for frequency and severity of symptoms, SANDE items, at screening & baseline > 25 mm (SANDE overall score > 25 mm).
4. 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)
5. 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)
6. Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units in both eyes at the time of study enrolment.
7. The Informed Consent by approved Ethics Committees should be signed by the subject before any study procedures.

Exclusion Criteria:

1. Evidence of an active ocular infection in either eye
2. History or presence of ocular surface disorders not related to dry eye in either eye
3. History or evidence of eyelid abnormality in either eye
4. 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
5. 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
6. 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.)
7. Known hypersensitivity to one of the components of the study or procedural medications
8. Participation in another clinical study at the same time as the present study or within 90 days of baseline visit
9. History of drug, medication or alcohol abuse or addiction.

10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lubricin; Lubricin 150 µg/ml eye drops solution	Device: Lubricin; Lubricin 150 µg/ml eye drops
Active Comparator: Sodium Hyaluronate; Sodium hyaluronate 0.13% eye drops	Device: Sodium Hyaluronate; Sodium hyaluronate 0.13% eye drops

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dompé Farmaceutici S.p.A
• Investigators: Principal Investigator: Caterina Gagliano, MD, Policlinico Vittorio Emanuele, Pres. Osp. G. Rodolico Clinica Oculistica

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: July 28, 2015
• First Posted (Estimate): July 29, 2015

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 28, 2019
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Dry Eye
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Xerophthalmia; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: LUB0114MD