Efficacy and Safety of Ikervis Under Controlled Environmental Conditions Environment

Study Overview
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Brief Summary
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The proposed study is a prospective, open-label, unicentric, phase IV clinical trial. This study is design to find new efficacy biomarkers for IKERVIS® (1mg/mL ciclosporin) eye drops after 1 and 3 month after initiation of therapy. Additionally, this study intends to investigate whether IKERVIS® will help patients to better overcome situations of desiccating stress by exposing them to an adverse controlled environment (ACE) and analyzing both clinical and molecular parameters.

Official Title
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A Phase IV Open-Label Clinical Trial to Evaluate the Efficacy of Ikervis® on Clinical Parameters and Molecular/Cellular Biomarkers in Dry Eye Patients With Severe Keratitis Who Have Not Improved Despite Regular Use of Tear Substitutes Before and After Exposure to an Adverse Controlled Environment

Conditions
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Dry Eye, Dry Eye Syndromes, Severe Keratitis

Intervention / Treatment
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* Drug: IKERVIS®1mg/mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years. Diagnosis of DED with Severe Keratitis who have not improved despite regular use of tear substitutes by an ophthalmologist, at least 2 months previously. Not stable (as defined by the two items below) under at least 2 months of constant and regular use of artificial tears (at least 4 drops a day) Fluorescein corneal staining ≥ 2 (Oxford scale) in both eyes. DEQ-5 > 6 points Use of at least 4 times daily of an ocular artificial tears. Any concomitant medication that may affect DED, ocular surface condition or vision, must have a start date at least 3 months prior to baseline and dosage is not expected to change during the study. Best corrected visual acuity (BCVA) of at least 0.1 logMar at 6 meters with each eye. Signature of written informed consent form and data protection form. Exclusion Criteria: Known allergy or sensitivity to the study product(s) or its components. Any ocular pathology other than DED. History of severe ocular inflammation other than that due to DED or infection in the 6 previous months to the study inclusion. Any ocular surgery or trauma that may affect corneal sensitivity and/or normal tear distribution in the 6 previous months or any ocular or systemic surgery or procedure planned during the study duration that may affect the study as assessed by principal investigator. History of refractive surgery in the previous 18 months. Contact lens use in the ONE previous month to study inclusion and during the duration of the study. Use of any ocular topical medication for pathologies other than DED. Use of any other ocular topical medication for DED other than artificial tears during the last ONE (steroids) or THREE months (ciclosporine, tacrolimus) . Any uncontrolled severe systemic disease that may affect the eye (except for Sjögren's syndrome) The start date of any systemic medication that may affect DED, ocular surface condition or vision is < 3 months prior to baseline or a change in dosage is anticipated during the study. Occlusion of the lacrimal puncta either surgically or with plugs within one month prior to study, or anticipated use of the same during the study. Pregnancy or breastfeeding. Current enrolments in an investigational drug or device study or participation in such a study within 30 day of entry into this study at baseline.

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
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IKERVIS® (1mg/mL ciclosporin) eye drops<br> | Drug: IKERVIS®1mg/mL<br>* One drop of study medication once daily in each eye at bedtime during 90 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal fluoresceing staining | Significant reduction in corneal fluorescein staining | V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment); V2 (30 days of treatment) vs V3 (90 days of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response against adverse environmental conditions | Significant differences in the percentage of patients suffering a worsening in clinical signs and/or symptoms following exposure to adverse environmental conditions | V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment) | 
| Molecular changes | Significant reduction in median expression of HLA-DR by conjunctival epithelial cells. | V1 (baseline) vs V2 (30 days of treatment); V1 (baseline) vs V3 (90 days of treatment) |