Phase 3 Study of OTX-101 in the Treatment of Keratoconjunctivitis Sicca

Study Overview
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Brief Summary
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This is a randomized, double-masked, vehicle-controlled study of the safety and efficacy of OTX-101 (0.09% cyclosporine nanomicellar solution) in the treatment of keratoconjunctivitis sicca to be conducted at approximately 50 sites.

Official Title
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A Randomized, Multicenter, Double-Masked, Vehicle-Controlled Study of the Safety and Efficacy of OTX-101 in the Treatment of Keratoconjunctivitis Sicca

Conditions
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Keratoconjunctivitis Sicca

Intervention / Treatment
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* Drug: cyclosporine
* Drug: vehicle of OTX-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of dry eye syndrome (KCS) for a period of at least 6 months Clinical diagnosis of bilateral KCS Lissamine green conjunctival staining sum score of ≥ 3 to ≤ 9 out of a total possible score of 12 (scoring excludes superior zones 2 and 4) in the same eye at both the Screening and Baseline Visits. Global symptom score (SANDE) ≥ 40 mm at both the Screening and Baseline Visits Corrected Snellen visual acuity (VA) of better than 20/200 in each eye. Exclusion Criteria: Use of cyclosporine ophthalmic emulsion 0.05% (Restasis®) within 3 months prior to the Screening Visit. Previous treatment failure (lack of efficacy) with cyclosporine ophthalmic emulsion 0.05% (Restasis). Diagnosis of Sjögren's disease ˃ 5 years prior to the Screening Visit. Clinical diagnosis or any history of seasonal and/or perennial allergic conjunctivitis. Use of systemic or topical medications within 7 days prior to the Screening Visit or during the study period that are known to cause dry eye. Use of any topical ophthalmic medications, prescription (including anti-glaucoma medications) or over the counter (including artificial tears), other than the assigned study medication during the study period. Current active eye disease other than dry wyw syndrome (i.e., any disease for which topical or systemic ophthalmic medication is necessary). History of herpes keratitis. Corneal transplant Corneal refractive surgery within 6 months prior to the Screening Visit or postoperative refractive surgery symptoms of dryness that have not resolved. Cataract surgery within 3 months prior to the Screening Visit.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OTX-101 0.09%<br>0.09% cyclosporine nanomicellar ophthalmic solution | Drug: cyclosporine<br> <br> * Other names: Seciera;|
| Placebo Comparator: Vehicle<br>vehicle of OTX-101 | Drug: vehicle of OTX-101<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tear Production | Percentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conjunctival Staining | change from baseline in total conjunctival staining score (lissamine green, modified National Eye Institute scale) at 12 weeks. Conjunctival Lissamine Green Staining Grades ranged from 0 (No punctate stain in zone) to 3 (Densely concentrated micropunctate stain spots) | Baseline and 12 weeks | 
| Central Corneal Staining | change from baseline in central corneal staining score (fluorescein, modified NEI/FDA scale) at 12 weeks. The Expanded National Eye Institute (NEI)/Industry Workshop Scale for Corneal Staining Score was used to grade each of the 5 areas of the cornea on a 0 (No punctate stain in area) to 4 (Severe diffuse (coalescent) macropunctate stain of the area) scale. | Baseline and 12 weeks | 
| Symptom Score | change from baseline in modified Symptom Assessment in Dry Eye (SANDE) score at 12 weeks. A modified SANDE instrument was used to evaluate dry eye symptoms at each visit. Subjects were asked to indicate: frequency of dry and irritated eyes on a scale of 0 (rarely) to 100 (all the time); and severity of dry eyes on a scale of 0 (very mild) to 100 (severe) The global symptom score is the square root of the frequency score times the severity score and will be completed at each visit. (range 0 to 100) Negative change from baseline indicates improvement. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KCS, dry eye, cyclosporine