Safety and Efficacy of KPI-121 in Subjects With Inflammatory Meibomian Gland Disease

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to determine the efficacy and safety of KPI-121 ophthalmic suspension compared to vehicle (placebo) in subjects with signs and symptoms of inflammatory meibomian gland disease.

Detailed Description
-----------------
This is a Phase II, multicenter, double-masked, randomized, vehicle-controlled, parallel-group study designed to evaluate the efficacy and safety of KPI-121 ophthalmic suspension versus vehicle in subjects with signs and symptoms of inflammatory meibomian gland disease. The product will be studied over 28 days, with 1-2 drops instilled in each eye four times daily (QID).

Official Title
-----------------
A Phase II, Double-Masked, Randomized, Vehicle-Controlled Study to Evaluate the Effect of KPI-121 0.25% Ophthalmic Suspension on Signs and Symptoms of Inflammatory Meibomian Gland Disease

Conditions
-----------------
Blepharitis

Intervention / Treatment
-----------------
* Drug: KPI-121
* Drug: Vehicle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a documented clinical diagnosis of inflammatory meibomian gland disease in both eyes. Exclusion Criteria: Known hypersensitivity/contraindication to study product(s) or components. Be currently receiving treatment for glaucoma, have history of or current glaucoma, or an IOP (intraocular pressure) over 21mmHg at Visit 1 (Screening) or Visit 2 (Randomization). Be unwilling to discontinue warm compress therapy, lid expression, or lid massage 14 days prior to Day 1 and for the duration of the study. Diagnosis of: ongoing ocular infection; severe/serious ocular condition that in judgment of Investigator could confound study assessments or limit compliance; severe/serious systemic disease or uncontrolled medical condition that in judgment of Investigator could confound study assessments or limit compliance; or have been exposed to an investigational drug within the 30 days prior to screening. Have had ocular surgery in the past 90 days or require ocular surgery during the study. In the opinion of Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle<br>Vehicle (placebo) dosed QID for up to 30 days in subjects with inflammatory meibomian gland disease | Drug: Vehicle<br>* The vehicle control has the same composition as KPI-121 0.25% ophthalmic suspension except it does not contain loteprednol etabonate. The vehicle is essentially isotonic and is buffered to maintain pH 5.0 - 7.0. It is a sterile, aqueous solution supplied in the same white, low-density polyethylene plastic dropper bottle with the same white, controlled-drop polyethylene tip and white polypropylene closure as KPI-121 0.25% ophthalmic suspension.<br>* Other names: Placebo;|
| Active Comparator: KPI-121 0.25% Ophthalmic Suspension<br>KPI-121 0.25% Ophthalmic Suspension dosed QID for up to 30 days in subjects with inflammatory meibomian gland disease | Drug: KPI-121<br>* KPI-121 drug product will be supplied in 0.25% strength as a suspension in opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. Subjects randomized to placebo control arm will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.<br>* Other names: Loteprednol etabonate;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Ocular Discomfort | Comparison of change from baseline in ocular discomfort 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 at Visit 4 (Day 15). | Visit 2 (Day 1) to Visit 4 (Day 15) | 
| Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline | Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group in subjects with greater baseline hyperemia at Visit 4 (Day 15). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal mild moderate severe very severe | Visit 2 (Day 1) to Visit 4 (Day 15) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Ocular Discomfort | Comparison of change from baseline in ocular discomfort 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 at Visit 6 (Day 29). | Visit 2 (Day 1) to Visit 6 (Day 29) | 
| Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline | Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group in the subgroup of subjects with greater hyperemia at baseline at Visit 6 (Day 29). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal mild moderate severe very severe | Visit 2 (Day 1) to Visit 6 (Day 29) | 
| Change From Baseline in Posterior Lid Margin Hyperemia | Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group at Visit 4 (Day 15). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal mild moderate severe very severe | Visit 2 (Day 1) to Visit 4 (Day 15) | 
| Change From Baseline in Posterior Lid Margin Hyperemia | Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group at Visit 6 (Day 29). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal mild moderate severe very severe | Visit 2 (Day 1) to Visit 6 (Day 29) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pain, Corticosteroid, Meibomian Gland Disease, Blepharitis, Eyelid, Ocular Discomfort