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

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

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 28 days, with 1-2 drops instilled in each eye four times daily (QID).

Study Overview

• Status: Completed
• Conditions: Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Intervention / Treatment: Drug: KPI-121; Drug: Placebo

Detailed Description

This is a Phase II, 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.

Approximately 400 subjects will be screened and up to 150 subjects will be randomized at up to 12 centers located in the United States. Subjects will be randomized to 1 of 2 study arms in an approximate 1:1 ratio. The study arms are: 1) KPI-121 0.25% ophthalmic suspension administered 1-2 drops in each eye QID for up to 28 days or 2) vehicle administered as 1-2 drops in each eye QID for up to 28 days.

This study will include up to 6 clinic visits over 6 weeks. At Visit 1 Screening (14 ± 1 days prior to Day 1), subjects who meet screening inclusion/exclusion criteria will begin a 2-week run-in period during which they will be treated with 1-2 drops of single-masked vehicle in each eye QID for 14 ± 1 days.

At Visit 2, Randomization (Day 1), subjects who continue to meet inclusion/exclusion criteria will be eligible for randomization to 1 of the 2 arms of the study (i.e., KPI-121 0.25% ophthalmic suspension or vehicle). Following randomization, subjects will be instructed to return to the clinic to have a complete study evaluation at Study Visits 4 and 6 (Days 15 ± 1 day and 29 ± 1 day, respectively). Subjects will further be instructed to return to the clinic for diary collection and in-clinic symptom assessment only at Visits 3 and 5 (Days 8 ± 1 day and 22 ± 1 day, respectively). The last dose of investigational product and the final study visit will occur upon completion of 28 ± 1 days of exposure to investigational product. Subjects will be released from the study at the end of Visit 6 (Day 29 ± 1 day).

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Artesia, California, United States, 90701
      • Sall Research Medical Center
    • Mission Hills, California, United States, 91345
      • North Valley Eye Medical Group
    • Rancho Cordova, California, United States, 95670
      • Martel Eye Medical Group
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Eye Center of Southern CT, P.C.
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Price Vision Group
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Ophthalmology Associates
    • Washington, Missouri, United States, 63090
      • Comprehensive Eye Care, Ltd. / Vision Research Institute, LLC
  • New York
    • Wantagh, New York, United States, 11793
      • South Shore Eye Center, LLP
  • Ohio
    • Cleveland, Ohio, United States, 44115
      • Abrams Eye Center
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care, PA
  • Texas
    • Houston, Texas, United States, 77055
      • Whitsett Vision Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a documented clinical diagnosis of dry eye disease in both eyes

Exclusion Criteria:

• Known hypersensitivity/contraindication to study product(s) or components.
• History of glaucoma, 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; 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.
• In the opinion of Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: KPI-121 0.25% Ophthalmic Suspension; KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease	Drug: KPI-121; KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.; Other Names: Loteprednol etabonate; KPI-121 0.25% Ophthalmic Suspension
Placebo Comparator: Vehicle; Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease	Drug: Placebo; Subjects randomized to placebo control arms 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.; Other Names: Vehicle of KPI-121 0.25% Ophthalmic Suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bulbar Conjunctival Hyperemia	Comparison of mean bulbar conjunctival hyperemia in the study eye 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 6 (Day 29)
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.	Visit 6 (Day 29)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal Fluorescein Staining Scores	Comparison of mean corneal fluorescein staining scores in the study eye 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. The total score is obtained by summing each of the 5 sections of the cornea. The NEI score will be from 0-15.	Visit 4 (Day 15) and Visit 6 (Day 29)
Bulbar Conjunctival Hyperemia Scores	Comparison of mean bulbar conjunctival hyperemia scores in the study eye 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)
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.	Visit 4 (Day 15)

Collaborators and Investigators

• Sponsor: Kala Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Gregg Berdy, MD, Ophthalmology Associates; Principal Investigator: David Evans, OD, Total Eye Care, PA; Principal Investigator: Kathy Kelley, OD, Price Vision Group; Principal Investigator: Joseph Martel, MD, Martel Eye Medical Group; Principal Investigator: Mark Milner, MD, Eye Center of Southern CT, P.C.; Principal Investigator: Steven Rauchman, MD, North Valley Eye Medical Group; Principal Investigator: Kenneth Sall, MD, Sall Research Medical Center; Principal Investigator: Jeffrey Whitsett, MD, Whitsett Vision Group; Principal Investigator: Marc Abrams, MD, Abrams Eye Center; Principal Investigator: Michael Korenfeld, MD, Ecomprehensive Eye Care, Ltd / Vision Research Institute LLC; Principal Investigator: Jodi Luchs, MD, South Shore Eye Center

Publications and helpful links

General Publications

• Korenfeld M, Nichols KK, Goldberg D, Evans D, Sall K, Foulks G, Coultas S, Brazzell K. Safety of KPI-121 Ophthalmic Suspension 0.25% in Patients With Dry Eye Disease: A Pooled Analysis of 4 Multicenter, Randomized, Vehicle-Controlled Studies. Cornea. 2021 May 1;40(5):564-570. doi: 10.1097/ICO.0000000000002452.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: July 9, 2014
• First Submitted That Met QC Criteria: July 10, 2014
• First Posted (Estimate): July 11, 2014

Study Record Updates

• Last Update Posted (Actual): January 6, 2021
• Last Update Submitted That Met QC Criteria: January 4, 2021
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Pain; Corticosteroid; Dry Eye; Ocular Discomfort; Hyperemia
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratoconjunctivitis; Anti-Allergic Agents; Loteprednol Etabonate
• Other Study ID Numbers: KPI-121-C-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO