Ocular Infections, Irritations and Inflammations
Conditions
Keywords
postsurgical, postoperative, ocular, cataract, inflammation, pain, corticosteroid
Brief summary
The primary purpose of this study is to determine the efficacy and safety of KPI-121 ophthalmic suspension compared to placebo in subjects who have undergone cataract surgery. The efficacy and safety of two different concentrations and two different dosing regimens of KPI-121 are also being assessed.
Detailed description
This is a Phase III, multicenter, double-masked, randomized, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of two doses and two dosing regimens of KPI-121 ophthalmic suspension versus placebo in subjects who require treatment of postoperative anterior ocular inflammation. Approximately 500 subjects will be screened and up to 402 subjects with one study eye each will be randomized in this study at approximately 25 centers located in the United States. Subjects who experience postoperative inflammation on the first day following routine, uncomplicated, cataract surgery and who meet all other eligibility criteria will be randomized to one of four study groups (0.25% four times daily or 1.0% two times daily) or Placebo A four times daily or Placebo B two times daily. Drug product or placebo will be initiated on the day following surgery and instilled as one to two drops in the study eye according to the assigned dosing regimen for 14 days. This study will include up to 7 clinic visits (including the surgery day) over 18 to 33 days total study duration. Visit 1 (Screening) will occur between 14 to 1 day(s) prior to surgery, and subjects who meet preoperative screening inclusion/exclusion criteria will be entered into the study. At Visit 2 (Surgery/Day 0) subjects will undergo routine cataract surgery according to the Investigator's normal procedures. Visit 3 (Randomization/Day 1) will occur on the day following surgery. Following randomization, subjects will be instructed to return to the clinic to be evaluated at Visit 4 (Day 3 +2 day), Visit 5 (Day 8 ±1 day), and Visit 6 (Day 15 ±1 day). The last dose of study product will be administered upon completion of 14 days of evaluation. Following the End of Study Product Use Visit (Visit 6; Day 15 ±1 day), subjects will be asked to return to the clinic on Day 17-19 for Visit 7 (Follow-Up) and will be released from the study.
Interventions
DRUGKPI-121 0.25%
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.
DRUGKPI-121 1.0%
KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
DRUGVehicle of KPI-121 0.25%
Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.
DRUGVehicle of KPI-121 1.0%
Placebo control arms will receive the same bottles containing vehicle of KPI-121 including 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
FURTHER STUDY DETAILS PROVIDED BY KALA PHARMACEUTICALS, INC. Inclusion Criteria: * Candidates for routine, uncomplicated cataract surgery * In Investigator's opinion, potential postoperative Snellen Distance VA by pinhole method of at least 20/200 in study eye.
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 or 19 days following surgery. * 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 |
|---|---|---|
| Resolution of Anterior Chamber Cells | Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15) | Subjects with complete resolution of anterior chamber cells (cell score = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6. 0= No cells seen 1. 1 to 5 cells 2. 6 to 15 cells 3. 16 to 30 cells 4. greater than 30 cells |
| Resolution of Ocular Pain | Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15) | Subjects with complete resolution of pain (grade = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anterior Chamber Cell Grade at Visit 5. | Visit 5 (postoperative day 8) | Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 5/Day 8. The difference in mean grade of AC cell count grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. 1 - 5 cells 2. 6 - 15 cells 3. 16 - 30 cells 4 = greater than 30 cells |
| Anterior Chamber Cell Grade at Visit 6. | Visit 6 (postoperative day 15) | Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 6/Day 15. The difference in mean grade of AC cell count grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. 1 - 5 cells 2. 6 - 15 cells 3. 16 - 30 cells 4 = greater than 30 cells |
| Ocular Pain Grades at Day 8. | Visit 5 (postoperative day 8) | Mean Grade of Ocular Pain (Scale 0-5) at Visit 5/Day 8. The difference in mean grade of ocular pain grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None 1. Minimal 2. Mild 3. Moderate 4. Moderately Severe 5. Severe |
| Ocular Pain Grades at Day 15. | Visit 6 (postoperative day 15) | Mean Grade of Ocular Pain (Scale 0-5) at Visit 6/Day 15. The difference in mean grade of ocular pain grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None 1. Minimal 2. Mild 3. Moderate 4. Moderately Severe 5. Severe |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| KPI-121 0.25% QID KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant.
KPI-121 0.25%: 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. | 129 |
| KPI-121 1.0% BID KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant.
KPI-121 1.0%: KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate. | 125 |
| Vehicle of KPI-121 Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily or 1.0% Ophthalmic Suspension dose 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant.
Vehicle of KPI-121: Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate. | 126 |
| Total | 380 |
Baseline characteristics
| Characteristic | KPI-121 0.25% QID | Total | Vehicle of KPI-121 | KPI-121 1.0% BID |
|---|---|---|---|---|
| Age, Continuous | 68.4 years | 68.7 years | 69.8 years | 67.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 36 Participants | 13 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 121 Participants | 344 Participants | 113 Participants | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants | 61 Participants | 21 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 30 Participants | 14 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 8 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 96 Participants | 274 Participants | 87 Participants | 91 Participants |
| Region of Enrollment United States | 129 participants | 380 participants | 126 participants | 125 participants |
| Sex: Female, Male Female | 73 Participants | 226 Participants | 78 Participants | 75 Participants |
| Sex: Female, Male Male | 56 Participants | 154 Participants | 48 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 129 | 0 / 125 | 0 / 126 |
| other Total, other adverse events | 13 / 129 | 6 / 125 | 20 / 126 |
| serious Total, serious adverse events | 2 / 129 | 1 / 125 | 2 / 126 |
Outcome results
Primary
Resolution of Anterior Chamber Cells
Subjects with complete resolution of anterior chamber cells (cell score = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6. 0= No cells seen 1. 1 to 5 cells 2. 6 to 15 cells 3. 16 to 30 cells 4. greater than 30 cells
Time frame: Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15)
Population: Intent to treat- all subjects randomized
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KPI-121 0.25% QID | Resolution of Anterior Chamber Cells | 48 Participants |
| KPI-121 1.0% BID | Resolution of Anterior Chamber Cells | 39 Participants |
| Vehicle of KPI-121 | Resolution of Anterior Chamber Cells | 19 Participants |
Comparison: All statistical tests of hypotheses performed for the pairwise comparison of means were two-sided.~All statistical tests employed a level of significance of alpha = 0.05.p-value: 0.002495% CI: [5.9, 26.4]Chi-squared
Comparison: All statistical tests of hypotheses performed for the pairwise comparison of means were two-sided.~All statistical tests employed a level of significance of alpha = 0.05.p-value: <0.000195% CI: [11.7, 32.6]Chi-squared
Primary
Resolution of Ocular Pain
Subjects with complete resolution of pain (grade = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6.
Time frame: Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15)
Population: Intent to Treat- all subjects randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KPI-121 0.25% QID | Resolution of Ocular Pain | 73 Participants |
| KPI-121 1.0% BID | Resolution of Ocular Pain | 67 Participants |
| Vehicle of KPI-121 | Resolution of Ocular Pain | 43 Participants |
Comparison: All statistical tests of hypotheses performed for the pairwise comparison of means were two-sided.~All statistical tests employed a level of significance of alpha = 0.05.p-value: 0.001995% CI: [7.4, 31.5]Chi-squared
Comparison: All statistical tests of hypotheses performed for the pairwise comparison of means were two-sided.~All statistical tests employed a level of significance of alpha = 0.05.p-value: 0.000395% CI: [10.6, 34.4]Chi-squared
Secondary
Anterior Chamber Cell Grade at Visit 5.
Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 5/Day 8. The difference in mean grade of AC cell count grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. 1 - 5 cells 2. 6 - 15 cells 3. 16 - 30 cells 4 = greater than 30 cells
Time frame: Visit 5 (postoperative 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 (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% QID | Anterior Chamber Cell Grade at Visit 5. | 0.7 score on a scale | Standard Deviation 0.73 |
| KPI-121 1.0% BID | Anterior Chamber Cell Grade at Visit 5. | 0.9 score on a scale | Standard Deviation 0.74 |
| Vehicle of KPI-121 | Anterior Chamber Cell Grade at Visit 5. | 1.0 score on a scale | Standard Deviation 0.86 |
p-value: 0.0007ANCOVA
p-value: 0.044ANCOVA
Secondary
Anterior Chamber Cell Grade at Visit 6.
Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 6/Day 15. The difference in mean grade of AC cell count grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen 1. 1 - 5 cells 2. 6 - 15 cells 3. 16 - 30 cells 4 = greater than 30 cells
Time frame: Visit 6 (postoperative 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% QID | Anterior Chamber Cell Grade at Visit 6. | 0.4 score on a scale | Standard Deviation 0.65 |
| KPI-121 1.0% BID | Anterior Chamber Cell Grade at Visit 6. | 0.5 score on a scale | Standard Deviation 0.69 |
| Vehicle of KPI-121 | Anterior Chamber Cell Grade at Visit 6. | 0.6 score on a scale | Standard Deviation 0.75 |
p-value: 0.0391ANCOVA
p-value: 0.1811ANCOVA
Secondary
Ocular Pain Grades at Day 15.
Mean Grade of Ocular Pain (Scale 0-5) at Visit 6/Day 15. The difference in mean grade of ocular pain grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None 1. Minimal 2. Mild 3. Moderate 4. Moderately Severe 5. Severe
Time frame: Visit 6 (postoperative 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% QID | Ocular Pain Grades at Day 15. | 0.2 score on a scale | Standard Deviation 0.5 |
| KPI-121 1.0% BID | Ocular Pain Grades at Day 15. | 0.2 score on a scale | Standard Deviation 0.51 |
| Vehicle of KPI-121 | Ocular Pain Grades at Day 15. | 0.3 score on a scale | Standard Deviation 0.73 |
p-value: 0.2589ANCOVA
p-value: 0.2132ANCOVA
Secondary
Ocular Pain Grades at Day 8.
Mean Grade of Ocular Pain (Scale 0-5) at Visit 5/Day 8. The difference in mean grade of ocular pain grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None 1. Minimal 2. Mild 3. Moderate 4. Moderately Severe 5. Severe
Time frame: Visit 5 (postoperative 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 (MEAN) | Dispersion |
|---|---|---|---|
| KPI-121 0.25% QID | Ocular Pain Grades at Day 8. | 0.4 score on a scale | Standard Deviation 0.74 |
| KPI-121 1.0% BID | Ocular Pain Grades at Day 8. | 0.4 score on a scale | Standard Deviation 0.64 |
| Vehicle of KPI-121 | Ocular Pain Grades at Day 8. | 0.5 score on a scale | Standard Deviation 0.89 |
p-value: 0.1953ANCOVA
p-value: 0.0307ANCOVA