Safety and Efficacy of KPI-121 in Subjects With Dry Eye Disease

Study Overview
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Brief Summary
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The primary purpose of this study is to determine the efficacy and safety of KPI-121 0.25% ophthalmic suspension compared to vehicle (placebo) in subjects who have a documented clinical diagnosis of dry eye disease. The product will be studied over 14 days, with 1-2 drops instilled in each eye four times daily (QID).

Detailed Description
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This is a Phase 3, multi-center, double-masked, randomized, vehicle-controlled, parallel-group study designed to evaluate the safety and efficacy of KPI-121 0.25% ophthalmic suspension versus vehicle in subjects with dry eye disease.

Official Title
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A Phase 3, Double-Masked, Randomized, Controlled Study of KPI-121 0.25% Ophthalmic Suspension Compared to Vehicle in Subjects With Dry Eye Disease

Conditions
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Dry Eye Syndromes, Keratoconjunctivitis Sicca

Intervention / Treatment
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* Drug: KPI-121 0.25% Ophthalmic Suspension
* Drug: Vehicle of KPI-121 0.25% Ophthalmic Suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a documented clinical diagnosis of dry eye disease in both eyes Exclusion Criteria: Known hypersensitivity or contraindication to the investigational product(s) or components History of glaucoma, Intraocular Pressure (IOP) >21 mmHg at the screening or randomization visits, or being treated for glaucoma in either eye. Diagnosis of: ongoing ocular infection; severe/serious ocular condition that in judgment of Investigator could confound study assessments or limit compliance; or have been exposed to an investigational drug within 30 days prior to screening. In the opinion of the Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.

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 |
| --- | --- |
| Active Comparator: KPI-121 0.25% Ophthalmic Suspension<br> | Drug: KPI-121 0.25% Ophthalmic Suspension<br> <br> * Other names: Loteprednol etabonate;|
| Placebo Comparator: Vehicle of KPI-121 0.25% Ophthalmic Suspension<br> | Drug: Vehicle of KPI-121 0.25% Ophthalmic Suspension<br> <br> * Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15) | Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe. | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) | Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) in Corneal Fluorescein Staining Score at Visit 4 (Day 15) | Comparison of mean corneal fluorescein staining between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe. | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) Ocular Discomfort Severity at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort | Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse, in a sub-group of participants with more severe ocular discomfort at baseline. | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Conjunctival Hyperemia Scores at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort at Baseline (Day 1) | Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe. | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | 
| Proportion of Subjects With ≥1 Improvement in Conjunctival Hyperemia at Visit 4 (Day 15) | Proportion of subjects with ≥1 improvement from baseline in conjunctival hyperemia scores. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe. | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) Conjunctival Hyperemia Scores at Visit 4 (Day 15) for the Mean of All Regions (Nasal, Temporal, Frontal) | Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe. | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | 
| Change in Ocular Discomfort Severity Scores Prior to Visit 3 (Day 8) Minus the Mean of the Scores to Baseline/Visit 2 (Day 1) | Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8) | 
| Change in Ocular Discomfort Severity Scores Prior to Visit 3 (Day 8) Minus Baseline/Visit 2 (Day 1) in the Subgroup of Participants With More Severe Ocular Discomfort. | Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8) | 
| Change in Ocular Discomfort Severity Scores on Day 4 (Diary) Minus Baseline/Visit 2 (Day 1) | Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8) | 
| Change in Ocular Discomfort Severity Scores on Day 4 Day 4 (Diary) Minus Baseline/Visit 2 (Day 1) in the Subgroup of Participants With More Severe Ocular Discomfort | Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse, in a sub-group of participants with more severe ocular discomfort at baseline. | Baseline/Visit 2 (Day 1) and to Visit 3 (Day 8) | 
| Change From Baseline/Visit 2 (Day 1) in Conjunctival Hyperemia Scores With a Day 1 Conjunctival Hyperemia Score of ≥ 2 in the Subgroup of Participants With More Severe Ocular Discomfort | Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale in a sub-group of participants with more severe ocular discomfort at baseline.. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe. | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | 
| Subjects With a Grade of 0 in Conjunctival Hyperemia Score at Visit 4 (Day 15) | Comparison of mean bulbar conjunctival hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe | Visit 4 (Day 15) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ocular Discomfort, Pain, Corticosteroid, Hyperemia, Dry Eye