LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy of LME636 compared to vehicle in the reduction of ocular symptoms and to evaluate the safety and tolerability of LME636, when administered topically for up to 42 days, in subjects with severe dry eye disease.

Detailed Description
-----------------
This study is organized into 2 phases. Following a 2-week identification phase, eligible subjects with severe dry eye disease (DED) will be randomized into the treatment phase and will be dispensed study treatment for 10 weeks.

Official Title
-----------------
A Randomized, Double-masked, Vehicle-controlled Study of LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease

Conditions
-----------------
Dry Eye

Intervention / Treatment
-----------------
* Biological: LME636 ophthalmic solution
* Biological: LME636 Vehicle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must sign written informed consent. Physician diagnosis of DED of at least 6 months prior to Visit 1. Must use artificial tears, gels, lubricants or re-wetting drops on a regular basis. Respond as often or constantly to the question How often do your eyes feel uncomfortable?. Best Corrected Visual Acuity (BCVA) of 55 or greater in each eye as measured by ETDRS at Visit 1. Other protocol-specified inclusion criteria may apply. Exclusion Criteria: Presence of any acute infection or non-infectious ocular condition in either eye within 1 month of Visit 1. Contact lens wearers, defined as individuals who cannot be without their contact lenses for the entire duration of the study. Any chronic ocular degenerative condition that in the opinion of the Investigator could possibly advance during the time course of the study. Use of biologics treatments, such as systemic biologic anti-cytokines, including anti-TNFα drugs, or immunosuppressive therapy for the treatment of severe systemic autoimmune disorders. Diseases or conditions affecting the ocular surface that are associated with clinically significant scarring and or destruction of conjunctiva and/or cornea. Unwilling to abstain from topical ocular non-prescription medications during the course of the study, including concomitant use of artificial tears, gels, lubricants, re-wetting drops, allergy drops, etc. after Visit 2. Use of nasal, inhaled, systemic (including injections), or topical corticosteroids within 30 days of Visit 1. Women of child-bearing potential unwilling to use effective contraception methods as defined in the protocol. Other protocol-specified exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LME636<br>LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye 3 times a day (TID) for 6 weeks | Biological: LME636 ophthalmic solution<br> <br> |
| Placebo Comparator: Vehicle<br>LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks | Biological: LME636 Vehicle<br>* Inactive ingredients used as a placebo comparator<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Global Ocular Discomfort Score at Day 71 | Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a visual analog scale (VAS) displayed on a handheld digital Pad (electronic patient-reported outcome (ePRO)). Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the product of the discomfort frequency score multiplied by the discomfort severity score. Improvement results in a reduction of the discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline. A negative change from baseline indicates improvement. | Baseline (Day 43), Day 71 | 
| Best Corrected Visual Acuity (BCVA) | Visual Acuity (VA) with the subject's best spectacles or other visual corrective devices was measured using an ETDRS visual acuity chart at 3 meters (10 feet) and reported in letters read correctly. An increase (gain) in letters read indicates improvement. Both eyes contributed to the analysis. | Baseline (Day 43), Day 57, Day 71, Day 85 | 
| Intraocular Pressure (IOP) | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry or Tonopen and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Both eyes contributed to the analysis. | Baseline (Day 43), Day 57, Day 71, Day 85 | 
| Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit | Ocular signs (cornea, lens, and iris/anterior chamber) were assessed by slit-lamp biomicroscopy. An increase indicates worsening. Only one eye contributed to the analysis. | Baseline (Day 43), Day 57, Day 71, Day 85 | 
| Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit | The dilated fundus examination was performed to evaluate the health of the vitreous, retina, macula, choroid, and optic nerve. An increase indicates worsening. Only one eye contributed to the analysis. | Baseline (Day 43), Day 57, Day 71, Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With More Than 20 Units Improvement in Global Ocular Discomfort Score From Baseline at Day 71 | Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a VAS displayed on a handheld ePRO. Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the product of the discomfort frequency score multiplied by the discomfort severity score. Improvement results in a reduction of the discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline. | Baseline (Day 43), Day 71 | 
| Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ) | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. LLOQ is defined as 0.25 ng/mL. | Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 | 
| Percentage of Subjects With Anti-LME636 Antibodies by Visit | Samples were collected and assessed for anti-LME636 antibodies. | Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LME636, dry eye disease, efficacy, ocular discomfort