Clinical trial NCT02510235: Tolerability, Safety and Efficacy of Lubricin vs Sodium Hyaluronate Eye Drops in Subjects With Moderate Dry Eye
Official title: A Multicenter, Randomized, Double-masked, Controlled, Non-inferiority Study to Evaluate Tolerability, Safety and Efficacy of Lubricin vs Sodium Hyaluronate in Subjects With Moderate Dry Eye.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dry Eye Syndrome
Tear Film Insufficiency
Keywords: Dry Eye
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2015-07-29
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a 4-week randomised (1:1), controlled, double-masked, non-inferiority clinical investigation in subjects with moderate dry eye disease. Subjects with moderate dry eye will be evaluated at screening (from day -14 to day -8), baseline (day 1), week 2 (day 14±2 days), week 4 (day 28±4 days, or early exit) and at week 5 (at least 7 days but not more than 9 days after V4).

Treatment duration 28 days (4weeks) ± 4 days (maximum total study duration 32 days).

During the Run-in period of 7 days only a saline solution 0.9%, Nebul®, was allowed to the subject in both eyes four times a day (QID) every 4 h±1 h. No ocular topical treatments were allowed, including artificial tears/lubricants.

During the follow-up period (7-9 days) only Sodium hyaluronate (Na-HY) 0.13% eye drops monodose supplied by the Investigator will be allowed, to all subjects participating to the study, in both eyes as needed.
Primary purpose: TREATMENT

Brief summary: The objective of the clinical investigation was to evaluate tolerability, safety and efficacy of the tested medical device, eye drop containing Lubricin 150 µg/mL, as compared with a standard sodium hyaluronate 0.13% eye drop solution in subjects with moderate dry eye disease.

Primary objective:

• Symptom Assessment in Dry Eye (SANDE)

Secondary objectives:

* Treatment-emergent adverse events (TEAEs);
* Visual analogue scale (VAS) for ocular tolerability (foreign body sensation, burning/stinging, itching, pain, stick feeling, blurred vision and photophobia);
* Tear film osmolarity;
* Assessment of best corrected distance visual acuity (BCDVA)
* Slit lamp examination (SLE) to assess the Eyelid - Meibomian glands, Eyelid Erythema, Eyelid Oedema, Lashes, Conjunctiva Erythema, Lens, Iris, Anterior Chamber, Corneal transparency, Corneal neovascularization;
* Tear film break-up time (TFBUT);
* Corneal fluorescein surface staining (scored using the Oxford scale);
* Schirmer-I test (without anaesthesia) values;
* Intraocular Pressure (IOP)

All parameters will be evaluated at screening visit, baseline (day 1), visit 3 (day 14±2) and visit 4 (day 28±4) and at follow-up (final visit) at least 7 days but not more than 9 days after the last treatment.

The results for both the SANDE questionnaire and adverse events are reported at the patient level, without distinguishing between Study Eye and Non-Study Eye. This approach reflects the overall condition and experiences of the patient rather than attributing outcomes to individual eyes.

The Study Eye was identified as the eye with the worst overall tolerability score at Visit 2 (Day 1).

Detailed description: This study is a multicenter, randomized, double-masked, controlled, non-inferiority study to evaluate tolerability, safety and efficacy of Lubricin eye drops versus sodium hyaluronate eye drops (Ocuyal®) administered four times a day for 4 weeks and 1 week follow-up in subjects with moderate dry eye.

Eligibility criteria: 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 form approved by the 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 test device or the comparator
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.

Primary outcomes:
measure: Change From Baseline (V2) in Frequency and Severity of Dry Eye Symptoms (SANDE) Questionnaire Scores at Day 28±4 (End of Treatment)
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
Secondary outcomes:
measure: Treatment-emergent Adverse Events (TEAEs), Including Adverse Device Effects (ADEs)
timeFrame: From Visit 2 (Day 1)" i.e., the day of the first IMD administration to Visit 5 - Final visit/Follow up - Day 31- 41
measure: Changes From Baseline (Visit 2, Day 1) in Ocular Tolerability Using a Visual Analogue Scale (VAS)
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
measure: Change From Baseline in Tear Film Osmolarity
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
measure: Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) - ETDRS Score
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
measure: Change From Baseline in Permanence of Lubricin on the Ocular Surface - Tear Film Break-up Time (TFBUT)
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
measure: Change From Baseline in Slit Lamp Examination (SLE) Values
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
measure: Change From Baseline in Corneal Fluorescein Surface Staining (Oxford Score)
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
measure: Change From Baseline in Schirmer's Test Type I (Without Anaesthesia)
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
measure: Change From Baseline in Intraocular Pressure (IOP)
timeFrame: Visit 3 - Day 14±2, Visit 4 - Day 28±4, Visit 5 - Final visit/Follow up - Day 31- 41
Other outcomes:
Locations:
city: Catania
country: Italy
facility: Azienda OspedalieroUniversitaria "Policlinico Vittorio Emanuele" Presidio Ospedaliero S.Marta Clinica oculistica
city: Messina
country: Italy
facility: Ambulatorio Studio delle Malattie della Superficie Oculare, Unità Operativa Complessa di Oftalmologia, Azienda Ospedaliero Universitaria di Messina
Study officials:
affiliation: Dompé farmaceutici
name: Flavio Mantelli, MD
role: STUDY_DIRECTOR
References: