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

Phase 2

Completed

• Conditions: Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Interventions: Drug: Placebo; Drug: KPI-121

• Registration Number: NCT02188160
• Lead Sponsor: Kala Pharmaceuticals, Inc.

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).

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 Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-07-09
• Study First Submitted QC: 2014-07-10
• Study First Posted: 2014-07-11
• Primary Completion: 2015-01
• Study Completion: 2015-03
• Disposition First Submitted: 2016-07-08
• Disposition First Submitted QC: 2016-07-08
• Disposition First Posted: 2016-07-12
• Status Verified: 2019-07
• Results First Submitted: 2020-11-25
• Results First Submitted QC: 2021-01-04
• Last Update Submitted: 2021-01-04
• Results First Posted: 2021-01-06
• Last Update Posted: 2021-01-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vehicle	Placebo	Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease
KPI-121 0.25% Ophthalmic Suspension	KPI-121	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease

Primary Outcome Measures

Name	Time	Method
Bulbar Conjunctival Hyperemia	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.
Ocular Discomfort	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

Name	Time	Method
Bulbar Conjunctival Hyperemia Scores	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.
Corneal Fluorescein Staining Scores	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.
Ocular Discomfort	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.

Trial Locations

Locations (11)

Eye Center of Southern CT, P.C.; 🇺🇸 Hamden, Connecticut, United States

Total Eye Care, PA; 🇺🇸 Memphis, Tennessee, United States

Martel Eye Medical Group; 🇺🇸 Rancho Cordova, California, United States

Sall Research Medical Center; 🇺🇸 Artesia, California, United States

North Valley Eye Medical Group; 🇺🇸 Mission Hills, California, United States

Price Vision Group; 🇺🇸 Indianapolis, Indiana, United States

Ophthalmology Associates; 🇺🇸 Saint Louis, Missouri, United States

Comprehensive Eye Care, Ltd. / Vision Research Institute, LLC; 🇺🇸 Washington, Missouri, United States

Abrams Eye Center; 🇺🇸 Cleveland, Ohio, United States

Whitsett Vision Group; 🇺🇸 Houston, Texas, United States

South Shore Eye Center, LLP; 🇺🇸 Wantagh, New York, United States