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

• Sponsor: Kala Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02188160
• Collaborator: (none)
• Enrollment: 150
• Locations: 11
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 13.6
• Patients Per Site Per Month: 1.5

Study Details

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
• 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: Jun 1, 2014
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Mar 1, 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 Names: Vehicle of KPI-121 0.25% Ophthalmic Suspension

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Sall Research Medical Center	Artesia	California	United States	90701
2	North Valley Eye Medical Group	Mission Hills	California	United States	91345
3	Martel Eye Medical Group	Rancho Cordova	California	United States	95670
4	Eye Center of Southern CT, P.C.	Hamden	Connecticut	United States	06518
5	Price Vision Group	Indianapolis	Indiana	United States	46260
6	Ophthalmology Associates	Saint Louis	Missouri	United States	63131
7	Comprehensive Eye Care, Ltd. / Vision Research Institute, LLC	Washington	Missouri	United States	63090
8	South Shore Eye Center, LLP	Wantagh	New York	United States	11793
9	Abrams Eye Center	Cleveland	Ohio	United States	44115
10	Total Eye Care, PA	Memphis	Tennessee	United States	38119
11	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)

• Study Protocol and Statistical Analysis Plan - Sep 26, 2014

More Information

Publications

None provided.

• Responsible Party: Kala Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02188160
• Other Study ID Numbers: KPI-121-C-002
• First Posted: Jul 11, 2014
• Last Update Posted: Jan 6, 2021
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kala Pharmaceuticals, Inc.: Pain; Corticosteroid; Dry Eye; Hyperemia; Ocular Discomfort
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Keratoconjunctivitis; Loteprednol Etabonate

Study Results

Participant Flow

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle
Arm/Group Description	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease 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.	Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease 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.
Period Title: Overall Study
STARTED	73	77
COMPLETED	72	76
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle	Total
Arm/Group Description	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease 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.	Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease 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.	Total of all reporting groups
Overall Participants	73	77	150
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.3 (17.17)	54.9 (12.29)	55.6 (14.83)
Sex: Female, Male (Count of Participants)
Female	53 72.6%	61 79.2%	114 76%
Male	20 27.4%	16 20.8%	36 24%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 20.5%	16 20.8%	31 20.7%
Not Hispanic or Latino	58 79.5%	61 79.2%	119 79.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 4.1%	4 5.2%	7 4.7%
Native Hawaiian or Other Pacific Islander	2 2.7%	1 1.3%	3 2%
Black or African American	10 13.7%	8 10.4%	18 12%
White	54 74%	63 81.8%	117 78%
More than one race	0 0%	1 1.3%	1 0.7%
Unknown or Not Reported	4 5.5%	0 0%	4 2.7%
Region of Enrollment (participants) [Number]
United States	73 100%	77 100%	150 100%

Outcome Measures

1. Primary Outcome

Title	Bulbar Conjunctival Hyperemia
Description	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.
Time Frame	Visit 6 (Day 29)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle
Arm/Group Description	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease 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.	Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease 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.
Measure Participants	73	77
Mean (Standard Deviation) [score on a scale]	1.22 (0.633)	1.36 (0.626)

2. Primary Outcome

Title	Ocular Discomfort
Description	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.
Time Frame	Visit 6 (Day 29)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle
Arm/Group Description	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease 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.	Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease 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.
Measure Participants	73	77
Mean (Standard Deviation) [score on a scale]	57.05 (23.892)	60.47 (19.770)

3. Secondary Outcome

Title	Corneal Fluorescein Staining Scores
Description	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.
Time Frame	Visit 4 (Day 15) and Visit 6 (Day 29)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle
Arm/Group Description	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease 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.	Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease 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.
Measure Participants	73	77
Visit 4 (Day 15)	6.15 (2.582)	7.00 (2.920)
Visit 6 (Day 29)	5.64 (2.889)	6.16 (3.445)

4. Secondary Outcome

Title	Bulbar Conjunctival Hyperemia Scores
Description	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.
Time Frame	Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle
Arm/Group Description	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease 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.	Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease 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.
Measure Participants	73	77
Mean (Standard Deviation) [score on a scale]	1.36 (0.586)	1.42 (0.676)

5. Secondary Outcome

Title	Ocular Discomfort
Description	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.
Time Frame	Visit 4 (Day 15)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension	Vehicle
Arm/Group Description	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease 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.	Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease 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.
Measure Participants	73	77
Mean (Standard Deviation) [score on a scale]	58.83 (20.745)	63.63 (17.844)

Adverse Events

Time Frame	Adverse event data was collected from Visit 2 (Day 1) through Visit 6 (Day 29).
Adverse Event Reporting Description	One Subject was randomized to KPI-121 0.25% but received vehicle. Therefore, 72 subjects are included in the KPI-121 0.25% group and 78 subjects are included in the vehicle group in the safety analyses.
Arm/Group Title	KPI-121 0.25% Ophthalmic Suspension		Vehicle
Arm/Group Description	KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease 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.		Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease 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.
All Cause Mortality
	KPI-121 0.25% Ophthalmic Suspension		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/72 (0%)		0/78 (0%)
Serious Adverse Events
	KPI-121 0.25% Ophthalmic Suspension		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/72 (1.4%)		0/78 (0%)
Hepatobiliary disorders
Cholelithiasis	1/72 (1.4%)	1	0/78 (0%)	0
Other (Not Including Serious) Adverse Events
	KPI-121 0.25% Ophthalmic Suspension		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/72 (9.7%)		8/78 (10.3%)
General disorders
Instillation site pain	7/72 (9.7%)	18	8/78 (10.3%)	16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The institution and Investigators participating in this trial shall have no right to publish or present the results of this study without the prior written consent of the sponsor.