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

• ClinicalTrials.gov Identifier: NCT02188160
• Recruitment Status: Completed
• First Posted: July 11, 2014
• Results First Posted: January 6, 2021
• Last Update Posted: January 6, 2021
• Sponsor: Kala Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Kala Pharmaceuticals, Inc.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Dry Eye Syndromes; Keratoconjunctivitis Sicca	Drug: KPI-121; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-Masked, Randomized, Controlled Study of KPI-121 0.25% Ophthalmic Suspension Compared to Vehicle in Subjects With Dry Eye Disease
• Study Start Date: June 2014
• Actual Primary Completion Date: January 2015
• Actual Study Completion Date: March 2015

Arms and Interventions

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: KPI-121 0.25% Ophthalmic Suspension; Loteprednol etabonate
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 Name: Vehicle of KPI-121 0.25% Ophthalmic Suspension

Outcome Measures

Primary Outcome Measures :

1. Bulbar Conjunctival Hyperemia [ Time Frame: Visit 6 (Day 29) ]
   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.
2. Ocular Discomfort [ Time Frame: Visit 6 (Day 29) ]
   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.

Secondary Outcome Measures :

1. Corneal Fluorescein Staining Scores [ Time Frame: Visit 4 (Day 15) and Visit 6 (Day 29) ]
   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.
2. Bulbar Conjunctival Hyperemia Scores [ Time Frame: Visit 4 (Day 15) ]
   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.
3. Ocular Discomfort [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Sall Research Medical Center

Artesia, California, United States, 90701

North Valley Eye Medical Group

Mission Hills, California, United States, 91345

Martel Eye Medical Group

Rancho Cordova, California, United States, 95670

United States, Connecticut

Eye Center of Southern CT, P.C.

Hamden, Connecticut, United States, 06518

United States, Indiana

Price Vision Group

Indianapolis, Indiana, United States, 46260

United States, Missouri

Ophthalmology Associates

Saint Louis, Missouri, United States, 63131

Comprehensive Eye Care, Ltd. / Vision Research Institute, LLC

Washington, Missouri, United States, 63090

United States, New York

South Shore Eye Center, LLP

Wantagh, New York, United States, 11793

United States, Ohio

Abrams Eye Center

Cleveland, Ohio, United States, 44115

United States, Tennessee

Total Eye Care, PA

Memphis, Tennessee, United States, 38119

United States, Texas

Whitsett Vision Group

Houston, Texas, United States, 77055

Sponsors and Collaborators

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

  Study Documents (Full-Text)

Documents provided by Kala Pharmaceuticals, Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] September 26, 2014

More Information

• Responsible Party: Kala Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02188160
• Other Study ID Numbers: KPI-121-C-002
• First Posted: July 11, 2014
• Results First Posted: January 6, 2021
• Last Update Posted: January 6, 2021
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Kala Pharmaceuticals, Inc.:

Pain; Corticosteroid; Dry Eye; Hyperemia; Ocular Discomfort

Additional relevant MeSH terms:

Keratoconjunctivitis Sicca; Dry Eye Syndromes; Eye Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Lacrimal Apparatus Diseases; Loteprednol Etabonate; Anti-Allergic Agents