Dry Eye Syndromes, Keratoconjunctivitis Sicca
Conditions
Keywords
Pain, Corticosteroid, Dry Eye, Hyperemia, Ocular Discomfort
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).
Interventions
DRUGKPI-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.
DRUGPlacebo
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.
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/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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| KPI-121 0.25% Ophthalmic Suspension 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. | 73 |
| Vehicle 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. | 77 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Use of an excluded medication | 0 | 1 |
Baseline characteristics
| Characteristic | KPI-121 0.25% Ophthalmic Suspension | Total | Vehicle |
|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 17.17 | 55.6 years STANDARD_DEVIATION 14.83 | 54.9 years STANDARD_DEVIATION 12.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 31 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 119 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 18 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 117 Participants | 63 Participants |
| Region of Enrollment United States | 73 participants | 150 participants | 77 participants |
| Sex: Female, Male Female | 53 Participants | 114 Participants | 61 Participants |
| Sex: Female, Male Male | 20 Participants | 36 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 78 |
| other Total, other adverse events | 7 / 72 | 8 / 78 |
| serious Total, serious adverse events | 1 / 72 | 0 / 78 |
Outcome results
Primary
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.
Time frame: Visit 6 (Day 29)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Bulbar Conjunctival Hyperemia | 1.22 score on a scale | Standard Deviation 0.633 |
| Vehicle | Bulbar Conjunctival Hyperemia | 1.36 score on a scale | Standard Deviation 0.626 |
Primary
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.
Time frame: Visit 6 (Day 29)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Ocular Discomfort | 57.05 score on a scale | Standard Deviation 23.892 |
| Vehicle | Ocular Discomfort | 60.47 score on a scale | Standard Deviation 19.77 |
Secondary
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.
Time frame: Visit 4 (Day 15)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Bulbar Conjunctival Hyperemia Scores | 1.36 score on a scale | Standard Deviation 0.586 |
| Vehicle | Bulbar Conjunctival Hyperemia Scores | 1.42 score on a scale | Standard Deviation 0.676 |
Secondary
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.
Time frame: Visit 4 (Day 15) and Visit 6 (Day 29)
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Corneal Fluorescein Staining Scores | Visit 4 (Day 15) | 6.15 score on a scale | Standard Deviation 2.582 |
| KPI-121 0.25% Ophthalmic Suspension | Corneal Fluorescein Staining Scores | Visit 6 (Day 29) | 5.64 score on a scale | Standard Deviation 2.889 |
| Vehicle | Corneal Fluorescein Staining Scores | Visit 4 (Day 15) | 7.00 score on a scale | Standard Deviation 2.92 |
| Vehicle | Corneal Fluorescein Staining Scores | Visit 6 (Day 29) | 6.16 score on a scale | Standard Deviation 3.445 |
Secondary
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.
Time frame: Visit 4 (Day 15)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Ocular Discomfort | 58.83 score on a scale | Standard Deviation 20.745 |
| Vehicle | Ocular Discomfort | 63.63 score on a scale | Standard Deviation 17.844 |