Blepharitis
Conditions
Keywords
Pain, Corticosteroid, Meibomian Gland Disease, Blepharitis, Eyelid, Ocular Discomfort
Brief summary
The primary purpose of this study is to determine the efficacy and safety of KPI-121 ophthalmic suspension compared to vehicle (placebo) in subjects with signs and symptoms of inflammatory meibomian gland disease.
Detailed description
This is a Phase II, multicenter, double-masked, randomized, vehicle-controlled, parallel-group study designed to evaluate the efficacy and safety of KPI-121 ophthalmic suspension versus vehicle in subjects with signs and symptoms of inflammatory meibomian gland disease. The product will be studied over 28 days, with 1-2 drops instilled in each eye four times daily (QID).
Interventions
DRUGKPI-121
KPI-121 drug product will be supplied in 0.25% strength as a suspension in opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. Subjects randomized to placebo control arm 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.
DRUGVehicle
The vehicle control has the same composition as KPI-121 0.25% ophthalmic suspension except it does not contain loteprednol etabonate. The vehicle is essentially isotonic and is buffered to maintain pH 5.0 - 7.0. It is a sterile, aqueous solution supplied in the same white, low-density polyethylene plastic dropper bottle with the same white, controlled-drop polyethylene tip and white polypropylene closure as 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 inflammatory meibomian gland disease in both eyes.
Exclusion criteria
* Known hypersensitivity/contraindication to study product(s) or components. * Be currently receiving treatment for glaucoma, have history of or current glaucoma, or an IOP (intraocular pressure) over 21mmHg at Visit 1 (Screening) or Visit 2 (Randomization). * Be unwilling to discontinue warm compress therapy, lid expression, or lid massage 14 days prior to Day 1 and for the duration of the study. * 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. * Have had ocular surgery in the past 90 days or require ocular surgery during the study. * 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 |
|---|---|---|
| Change From Baseline in Ocular Discomfort | Visit 2 (Day 1) to Visit 4 (Day 15) | Comparison of change from baseline in ocular discomfort 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 at Visit 4 (Day 15). |
| Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline | Visit 2 (Day 1) to Visit 4 (Day 15) | Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group in subjects with greater baseline hyperemia at Visit 4 (Day 15). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal 1. mild 2. moderate 3. severe 4. very severe |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Ocular Discomfort | Visit 2 (Day 1) to Visit 6 (Day 29) | Comparison of change from baseline in ocular discomfort 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 at Visit 6 (Day 29). |
| Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline | Visit 2 (Day 1) to Visit 6 (Day 29) | Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group in the subgroup of subjects with greater hyperemia at baseline at Visit 6 (Day 29). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal 1. mild 2. moderate 3. severe 4. very severe |
| Change From Baseline in Posterior Lid Margin Hyperemia | Visit 2 (Day 1) to Visit 4 (Day 15) | Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group at Visit 4 (Day 15). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal 1. mild 2. moderate 3. severe 4. very severe |
Countries
United States
Participant flow
Pre-assignment details
206 subjects were randomized, 1 of which were not included in any analysis population as the individual did not receive randomized treatment.
Participants by arm
| Arm | Count |
|---|---|
| Vehicle Vehicle (placebo) dosed QID for up to 30 days in subjects with inflammatory meibomian gland disease
Vehicle: The vehicle control has the same composition as KPI-121 0.25% ophthalmic suspension except it does not contain loteprednol etabonate. The vehicle is essentially isotonic and is buffered to maintain pH 5.0 - 7.0. It is a sterile, aqueous solution supplied in the same white, low-density polyethylene plastic dropper bottle with the same white, controlled-drop polyethylene tip and white polypropylene closure as KPI-121 0.25% ophthalmic suspension. | 101 |
| KPI-121 0.25% Ophthalmic Suspension KPI-121 0.25% Ophthalmic Suspension dosed QID for up to 30 days in subjects with inflammatory meibomian gland disease
KPI-121: KPI-121 drug product will be supplied in 0.25% strength as a suspension in opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. Subjects randomized to placebo control arm 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. | 104 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Vehicle | Total | KPI-121 0.25% Ophthalmic Suspension |
|---|---|---|---|
| Age, Continuous | 58.6 years STANDARD_DEVIATION 13.13 | 59.4 years STANDARD_DEVIATION 12.22 | 60.2 years STANDARD_DEVIATION 11.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 63 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 142 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 26 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 80 Participants | 164 Participants | 84 Participants |
| Region of Enrollment United States | 101 participants | 205 participants | 104 participants |
| Sex: Female, Male Female | 72 Participants | 134 Participants | 62 Participants |
| Sex: Female, Male Male | 29 Participants | 71 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 104 |
| other Total, other adverse events | 8 / 101 | 8 / 104 |
| serious Total, serious adverse events | 0 / 101 | 0 / 104 |
Outcome results
Primary
Change From Baseline in Ocular Discomfort
Comparison of change from baseline in ocular discomfort 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 at Visit 4 (Day 15).
Time frame: Visit 2 (Day 1) to Visit 4 (Day 15)
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change From Baseline in Ocular Discomfort | -4.1 score on a scale | Standard Deviation 13.8 |
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline in Ocular Discomfort | -2.4 score on a scale | Standard Deviation 16.7 |
Primary
Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline
Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group in subjects with greater baseline hyperemia at Visit 4 (Day 15). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal 1. mild 2. moderate 3. severe 4. very severe
Time frame: Visit 2 (Day 1) to Visit 4 (Day 15)
Population: m1ITT- a subset of the ITT population with greater baseline hyperemia
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline | -0.5 score on a scale | Standard Deviation 0.7 |
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline | -04 score on a scale | Standard Deviation 0.7 |
Secondary
Change From Baseline in Ocular Discomfort
Comparison of change from baseline in ocular discomfort 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 at Visit 6 (Day 29).
Time frame: Visit 2 (Day 1) to Visit 6 (Day 29)
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change From Baseline in Ocular Discomfort | -8.2 score on a scale | Standard Deviation 17.1 |
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline in Ocular Discomfort | -5.0 score on a scale | Standard Deviation 15.8 |
Secondary
Change From Baseline in Posterior Lid Margin Hyperemia
Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group at Visit 4 (Day 15). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal 1. mild 2. moderate 3. severe 4. very severe
Time frame: Visit 2 (Day 1) to Visit 4 (Day 15)
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change From Baseline in Posterior Lid Margin Hyperemia | -0.56 score on a scale | Standard Deviation 0.72 |
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline in Posterior Lid Margin Hyperemia | -0.55 score on a scale | Standard Deviation 0.64 |
Secondary
Change From Baseline in Posterior Lid Margin Hyperemia
Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group at Visit 6 (Day 29). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal 1. mild 2. moderate 3. severe 4. very severe
Time frame: Visit 2 (Day 1) to Visit 6 (Day 29)
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change From Baseline in Posterior Lid Margin Hyperemia | -0.63 score on a scale | Standard Deviation 0.76 |
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline in Posterior Lid Margin Hyperemia | -0.65 score on a scale | Standard Deviation 0.8 |
Secondary
Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline
Comparison of change from baseline in posterior lid margin hyperemia between the KPI-121 0.25% ophthalmic suspension group and the vehicle group in the subgroup of subjects with greater hyperemia at baseline at Visit 6 (Day 29). The scale for posterior lid margin hyperemia was scored on a range from 0-4 with the following description: 0=normal 1. mild 2. moderate 3. severe 4. very severe
Time frame: Visit 2 (Day 1) to Visit 6 (Day 29)
Population: m1ITT- a subset of the ITT population with greater baseline hyperemia. m1ITT 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 |
|---|---|---|---|
| Vehicle | Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline | -0.4 score on a scale | Standard Deviation 0.7 |
| KPI-121 0.25% Ophthalmic Suspension | Change From Baseline in Posterior Lid Margin Hyperemia in the Subgroup of Subjects With Greater Hyperemia at Baseline | -0.6 score on a scale | Standard Deviation 0.7 |