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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).
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| KPI-121 0.25% Ophthalmic Suspension | Active Comparator | KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease |
|
| Vehicle | Placebo Comparator | Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KPI-121 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Visit 6 (Day 29) |
| 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. | Visit 6 (Day 29) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
• Have a documented clinical diagnosis of dry eye disease in both eyes
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sall Research Medical Center | Artesia | California | 90701 | United States | ||
| North Valley Eye Medical Group |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32826644 | Derived | Korenfeld M, Nichols KK, Goldberg D, Evans D, Sall K, Foulks G, Coultas S, Brazzell K. Safety of KPI-121 Ophthalmic Suspension 0.25% in Patients With Dry Eye Disease: A Pooled Analysis of 4 Multicenter, Randomized, Vehicle-Controlled Studies. Cornea. 2021 May 1;40(5):564-570. doi: 10.1097/ICO.0000000000002452. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 26, 2014 |
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| Placebo | Drug | 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. |
|
|
| Visit 4 (Day 15) and Visit 6 (Day 29) |
| 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. | Visit 4 (Day 15) |
| 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. | Visit 4 (Day 15) |
| Ecomprehensive Eye Care, Ltd / Vision Research Institute LLC |
| Principal Investigator |
| Jodi Luchs, MD | South Shore Eye Center | Principal Investigator |
| Mission Hills |
| California |
| 91345 |
| United States |
| Martel Eye Medical Group | Rancho Cordova | California | 95670 | United States |
| Eye Center of Southern CT, P.C. | Hamden | Connecticut | 06518 | United States |
| Price Vision Group | Indianapolis | Indiana | 46260 | United States |
| Ophthalmology Associates | St Louis | Missouri | 63131 | United States |
| Comprehensive Eye Care, Ltd. / Vision Research Institute, LLC | Washington | Missouri | 63090 | United States |
| South Shore Eye Center, LLP | Wantagh | New York | 11793 | United States |
| Abrams Eye Center | Cleveland | Ohio | 44115 | United States |
| Total Eye Care, PA | Memphis | Tennessee | 38119 | United States |
| Whitsett Vision Group | Houston | Texas | 77055 | United States |
| FG001 |
| 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | Visit 6 (Day 29) |
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| 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | Visit 6 (Day 29) |
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| 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | Visit 4 (Day 15) and Visit 6 (Day 29) |
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| 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | Visit 4 (Day 15) |
|
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| 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | Visit 4 (Day 15) |
|
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Adverse event data was collected from Visit 2 (Day 1) through Visit 6 (Day 29).
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 72 | 1 | 72 | 7 | 72 |
| EG001 | 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. | 0 | 78 | 0 | 78 | 8 | 78 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholelithiasis | Hepatobiliary disorders | MedDRA Version 16.1. | Non-systematic Assessment | One subject reported an SAE (cholelithiasis; KPI-121 0.25% group), which was considered unrelated to the study treatment; it was severe in intensity, led the subject to discontinue the study treatment, and ultimately resolved without sequelae. |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Instillation site pain | General disorders | MedDRA Version 16.1. | Non-systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| VP, Clinical Development | Kala Pharmaceuticals, Inc. | 781-996-5252 | results002@kalarx.com |
| Nov 25, 2020 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D015352 | Dry Eye Syndromes |
| D007638 | Keratoconjunctivitis Sicca |
| D010146 | Pain |
| D006940 | Hyperemia |
| ID | Term |
|---|---|
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
| D007637 | Keratoconjunctivitis |
| D003231 | Conjunctivitis |
| D003229 | Conjunctival Diseases |
| D007634 | Keratitis |
| D003316 | Corneal Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000069559 | Loteprednol Etabonate |
| ID | Term |
|---|---|
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
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|---|---|
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