Kerato Conjunctivitis Sicca
Conditions
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 14 days, with 1-2 drops instilled in each eye four times daily (QID).
Detailed description
This is a Phase 3, 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.
Interventions
DRUGKPI-121 Ophthalmic Suspension
KPI-121 Ophthalmic Suspension
DRUGVehicle
Vehicle for KPI-121 0.25% ophthalmic suspension
Sponsors
Kala Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a documented clinical diagnosis of dry eye disease in both eyes
Exclusion criteria
* Known hypersensitivity or contraindication to the investigational 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; or have been exposed to an investigational drug within 30 days prior to screening. * In the opinion of the Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) | Baseline/Visit 2 (Day 1) and to 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. |
| Change From Baseline/Visit 2 (Day 1) Ocular Discomfort Severity at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort | Baseline/Visit 2 (Day 1) and to 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, in a sub-group of participants with more severe ocular discomfort at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Conjunctival Hyperemia Scores at Visit 4 (Day 15) by Alternate Assessor | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | Comparison of mean bulbar conjunctival hyperemia 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. |
| Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15) | Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15) | Comparison of mean bulbar conjunctival hyperemia 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. |
| Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) Using 7 Day Mean | Baseline/Visit 2 (Day 1) to 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. |
| Change From Baseline/Visit 2 (Day 1) in Corneal Fluorescein Staining Score at Visit 4 (Day 15) | Baseline/Visit 2 (Day 1) to Visit 4 (Day 15) | Comparison of mean corneal fluorescein staining 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. |
| Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 3 (Day 8) | Baseline/Visit 2 (Day 1) to Visit 3 (Day 8) | 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. |
Countries
United States
Participant flow
Pre-assignment details
901 subjects were randomized and all were included in the ITT population.
Participants by arm
| Arm | Count |
|---|---|
| KPI-121 0.25% Ophthalmic Suspension KPI-121 Ophthalmic Suspension: KPI-121 Ophthalmic Suspension | 447 |
| Vehicle of KPI-121 0.25% Ophthalmic Suspension Vehicle: Vehicle for KPI-121 0.25% ophthalmic suspension | 454 |
| Total | 901 |
Baseline characteristics
| Characteristic | KPI-121 0.25% Ophthalmic Suspension | Total | Vehicle of KPI-121 0.25% Ophthalmic Suspension |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 15.26 | 57.4 years STANDARD_DEVIATION 15.39 | 57.3 years STANDARD_DEVIATION 15.53 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 26 Participants | 63 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 71 Participants | 144 Participants | 73 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 348 Participants | 689 Participants | 341 Participants |
| Region of Enrollment United States | 447 participants | 901 participants | 454 participants |
| Sex: Female, Male Female | 339 Participants | 669 Participants | 330 Participants |
| Sex: Female, Male Male | 108 Participants | 232 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 449 | 0 / 452 |
| other Total, other adverse events | 39 / 449 | 26 / 452 |
| serious Total, serious adverse events | 3 / 449 | 1 / 452 |
Outcome results
Primary
Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at 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.
Time frame: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)
Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) | -13.58 score on a scale | Standard Deviation 19.379 |
| Vehicle of KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) | -8.91 score on a scale | Standard Deviation 17.579 |
Primary
Change From Baseline/Visit 2 (Day 1) Ocular Discomfort Severity at Visit 4 (Day 15) in the Subgroup of Participants With More Severe 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, in a sub-group of participants with more severe ocular discomfort at baseline.
Time frame: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)
Population: Sub-group of Intent to Treat population with more severe ocular discomfort minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) Ocular Discomfort Severity at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort | -15.59 score on a scale | Standard Deviation 20.373 |
| Vehicle of KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) Ocular Discomfort Severity at Visit 4 (Day 15) in the Subgroup of Participants With More Severe Ocular Discomfort | -10.15 score on a scale | Standard Deviation 18.739 |
Secondary
Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15)
Comparison of mean bulbar conjunctival hyperemia 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: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)
Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15) | -0.35 score on a scale | Standard Deviation 0.575 |
| Vehicle of KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15) | -0.18 score on a scale | Standard Deviation 0.546 |
Secondary
Change From Baseline/Visit 2 (Day 1) in Corneal Fluorescein Staining Score at Visit 4 (Day 15)
Comparison of mean corneal fluorescein staining 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.
Time frame: Baseline/Visit 2 (Day 1) to Visit 4 (Day 15)
Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Corneal Fluorescein Staining Score at Visit 4 (Day 15) | -0.53 score on a scale | Standard Deviation 0.8 |
| Vehicle of KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Corneal Fluorescein Staining Score at Visit 4 (Day 15) | -0.43 score on a scale | Standard Deviation 0.739 |
Secondary
Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 3 (Day 8)
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: Baseline/Visit 2 (Day 1) to Visit 3 (Day 8)
Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 3 (Day 8) | -8.05 score on a scale | Standard Deviation 15.009 |
| Vehicle of KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 3 (Day 8) | -5.83 score on a scale | Standard Deviation 15.176 |
Secondary
Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) Using 7 Day Mean
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: Baseline/Visit 2 (Day 1) to Visit 4 (Day 15)
Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) Using 7 Day Mean | -11.76 score on a scale | Standard Deviation 18.035 |
| Vehicle of KPI-121 0.25% Ophthalmic Suspension | Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) Using 7 Day Mean | -7.91 score on a scale | Standard Deviation 16.298 |
Secondary
Change in Conjunctival Hyperemia Scores at Visit 4 (Day 15) by Alternate Assessor
Comparison of mean bulbar conjunctival hyperemia 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: Baseline/Visit 2 (Day 1) and to Visit 4 (Day 15)
Population: Intent to Treat population minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Change in Conjunctival Hyperemia Scores at Visit 4 (Day 15) by Alternate Assessor | -0.61 score on a scale | Standard Deviation 0.646 |
| Vehicle of KPI-121 0.25% Ophthalmic Suspension | Change in Conjunctival Hyperemia Scores at Visit 4 (Day 15) by Alternate Assessor | -0.48 score on a scale | Standard Deviation 0.657 |