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Safety and Efficacy of KPI-121 in Subjects With Postsurgical Inflammation and Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02793817
Recruitment Status : Completed
First Posted : June 8, 2016
Results First Posted : April 17, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Kala Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Post Surgical Ocular Inflammation and Pain
Interventions Drug: KPI-121 1% Ophthalmic Suspension dosed BID
Drug: Vehicle of KPI-121 Ophthalmic Suspension dosed BID
Enrollment 520
Recruitment Details  
Pre-assignment Details  
Arm/Group Title KPI-121 1.0% Ophthalmic Suspension Vehicle of KPI-121 Ophthalmic Suspension
Hide Arm/Group Description

dosed BID

KPI-121 1% Ophthalmic Suspension dosed BID

dosed BID

Vehicle of KPI-121 Ophthalmic Suspension dosed BID

Period Title: Overall Study
Started 261 259
Completed 258 254
Not Completed 3 5
Arm/Group Title KPI-121 1.0% Ophthalmic Suspension Vehicle of KPI-121 Ophthalmic Suspension Total
Hide Arm/Group Description

dosed BID

KPI-121 1% Ophthalmic Suspension dosed BID

dosed BID

Vehicle of KPI-121 Ophthalmic Suspension dosed BID

Total of all reporting groups
Overall Number of Baseline Participants 261 259 520
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 261 participants 259 participants 520 participants
67.5
(38 to 89)
69.3
(40 to 90)
68.4
(38 to 90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 259 participants 520 participants
Female
144
  55.2%
144
  55.6%
288
  55.4%
Male
117
  44.8%
115
  44.4%
232
  44.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 259 participants 520 participants
Hispanic or Latino
38
  14.6%
36
  13.9%
74
  14.2%
Not Hispanic or Latino
223
  85.4%
223
  86.1%
446
  85.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 259 participants 520 participants
American Indian or Alaska Native
1
   0.4%
1
   0.4%
2
   0.4%
Asian
17
   6.5%
19
   7.3%
36
   6.9%
Native Hawaiian or Other Pacific Islander
2
   0.8%
2
   0.8%
4
   0.8%
Black or African American
27
  10.3%
24
   9.3%
51
   9.8%
White
206
  78.9%
207
  79.9%
413
  79.4%
More than one race
2
   0.8%
0
   0.0%
2
   0.4%
Unknown or Not Reported
6
   2.3%
6
   2.3%
12
   2.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 261 participants 259 participants 520 participants
261 259 520
1.Primary Outcome
Title Complete Resolution of Anterior Chamber (AC) Cells at Day 8
Hide Description

Number and percentage of subjects with complete resolution of AC cells in the surgical eye (study eye) at Day 8 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID.

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 (Day 8) maintained through Visit 6 (Day 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat - All subjects randomized
Arm/Group Title KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Hide Arm/Group Description:
KPI-121 1% Ophthalmic Suspension dosed BID
Vehicle of KPI-121 1% Ophthalmic Suspension dosed BID
Overall Number of Participants Analyzed 261 259
Measure Type: Count of Participants
Unit of Measure: Participants
54
  20.7%
32
  12.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KPI-121 1% Ophthalmic Suspension, Vehicle of KPI-121 1% Ophthalmic Suspension
Comments P-values were based on 2-sided chi-squared tests (unadjusted) wherein the a priori significance level was 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0105
Comments To account for multiplicity, a step-down testing procedure was applied, whereby inference for a test in the pre-defined hierarchy was dependent upon statistical significance having been demonstrated for the previous test in the hierarchy.
Method Chi-squared
Comments Without adjustment for any covariates
Method of Estimation Estimation Parameter Difference in percentage of responders
Estimated Value 8.3
Confidence Interval (2-Sided) 95%
2.0 to 14.7
Estimation Comments Estimated Value is the between-group difference for % of responders and is expressed as a percentage.
2.Primary Outcome
Title Complete Resolution of Ocular Pain at Day 8
Hide Description

Number and percentage of subjects with complete resolution of ocular pain in the surgical eye (study eye) at Day 8 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID.

Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain at Days 1, 4, 8, 15, and the follow-up visit between Days 17 and 19. 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 (Day 8) maintained through Visit 6 (Day 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat - All subjects randomized
Arm/Group Title KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Hide Arm/Group Description:
KPI-121 1% Ophthalmic Suspension dosed BID
Vehicle of KPI-121 1% Ophthalmic Suspension dosed BID
Overall Number of Participants Analyzed 261 259
Measure Type: Count of Participants
Unit of Measure: Participants
149
  57.1%
96
  37.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KPI-121 1% Ophthalmic Suspension, Vehicle of KPI-121 1% Ophthalmic Suspension
Comments P-values were based on 2-sided chi-squared test (unadjusted), wherein a priori significance level was 0.05
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To account for multiplicity, a step-down closed testing procedure was applied, whereby inference for a test in the pre-defined hierarchy was dependent upon statistical significance having been demonstrated for the previous test in the hierarchy.
Method Chi-squared
Comments Without adjustment for any covariates
Method of Estimation Estimation Parameter Difference in percentage of responders
Estimated Value 20.0
Confidence Interval (2-Sided) 95%
11.6 to 28.4
Estimation Comments Estimated Value is the between-group difference for % of responders and is expressed as a percentage.
3.Secondary Outcome
Title Complete Resolution of Ocular Pain at Day 4
Hide Description

Number and percentage of subjects with complete resolution of ocular pain in the surgical eye (study eye) at Day 4 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID.

Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain at Days 1, 4, 8, 15, and the follow-up visit between Days 17 and 19. 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 4 (Day 4) maintained through Visit 6 (Day 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat - All subjects randomized
Arm/Group Title KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Hide Arm/Group Description:
KPI-121 1% Ophthalmic Suspension dosed BID
Vehicle of KPI-121 1% Ophthalmic Suspension dosed BID
Overall Number of Participants Analyzed 261 259
Measure Type: Count of Participants
Unit of Measure: Participants
109
  41.8%
64
  24.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KPI-121 1% Ophthalmic Suspension, Vehicle of KPI-121 1% Ophthalmic Suspension
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was based on a 2-sided chi-squared test (unadjusted) wherein the a priori significance level was 0.0167 for each secondary endpoint. Overall alpha for all secondary endpoints was controlled at 0.05.
Method Chi-squared
Comments Without adjustment for any covariates
Method of Estimation Estimation Parameter Difference in percentage of responders
Estimated Value 17.1
Confidence Interval (2-Sided) 95%
9.1 to 25.0
Estimation Comments Estimated Value is the between-group difference for % of responders and is expressed as a percentage.
4.Secondary Outcome
Title Complete Resolution of Anterior Chamber (AC) Flare at Day 4
Hide Description

Number and percentage of subjects with complete resolution of AC flare in the surgical eye (study eye) at Day 4 maintained through Day 15, without receiving rescue medication prior to Day 15, for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID.

Investigators were asked to grade AC flare based on the following scale wherein higher scores indicate a higher degree of flare present and a decrease across time indicates the condition is getting better.

Anterior Chamber Flare 0 = None

  1. = Mild (trace to clearly noticeable, visible)
  2. = Moderate (without plastic aqueous humor)
  3. = Marked (with plastic aqueous humor)
  4. = Severe (with fibrin deposits and/or clots)
Time Frame Visit 4 (Day 4) maintained through Visit 6 (Day 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat - All subjects randomized
Arm/Group Title KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Hide Arm/Group Description:
KPI-121 1% Ophthalmic Suspension dosed BID
Vehicle of KPI-121 1% Ophthalmic Suspension dosed BID
Overall Number of Participants Analyzed 261 259
Measure Type: Count of Participants
Unit of Measure: Participants
113
  43.3%
63
  24.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KPI-121 1% Ophthalmic Suspension, Vehicle of KPI-121 1% Ophthalmic Suspension
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was based on a 2-sided chi-squared test (unadjusted) wherein the a priori significance level was 0.0167 for each secondary endpoint. Overall alpha for all secondary endpoints was controlled at 0.05.
Method Chi-squared
Comments Without adjustment for any covariates
Method of Estimation Estimation Parameter Difference in percentage of responders
Estimated Value 19.0
Confidence Interval (2-Sided) 95%
11.0 to 26.9
Estimation Comments Estimated Value is the between-group difference for % of responders and is expressed as a percentage.
5.Secondary Outcome
Title Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 4
Hide Description

The difference in mean changes from BL in AC cell count grade at Day 4 for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID.

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 1 (Baseline) and Visit 4 (Day 4)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat - All subjects randomized
Arm/Group Title KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Hide Arm/Group Description:
KPI-121 1% Ophthalmic Suspension dosed BID
Vehicle of KPI-121 1% Ophthalmic Suspension dosed BID
Overall Number of Participants Analyzed 258 257
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.7  (0.84) -0.5  (0.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KPI-121 1% Ophthalmic Suspension, Vehicle of KPI-121 1% Ophthalmic Suspension
Comments P-value was based on a 2-sided chi-squared test (unadjusted) wherein the a priori significance level was 0.0167 for each secondary endpoint. Overall alpha for all secondary endpoints was controlled at 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0078
Comments [Not Specified]
Method Chi-squared
Comments Without adjustment for any covariates
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.31 to -0.05
Estimation Comments Estimated Value is the between-group difference for change from BL.
6.Post-Hoc Outcome
Title Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 8
Hide Description

The difference in mean changes from BL in AC cell count grade at Day 8 for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID.

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 1 (Baseline) and Visit 5 (Day 8)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat - All subjects randomized
Arm/Group Title KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Hide Arm/Group Description:
KPI-121 1% Ophthalmic Suspension dosed BID
Vehicle of KPI-121 1% Ophthalmic Suspension dosed BID
Overall Number of Participants Analyzed 258 257
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.3  (0.90) -1.0  (0.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KPI-121 1% Ophthalmic Suspension, Vehicle of KPI-121 1% Ophthalmic Suspension
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments P-values have no inferential value for post hoc evaluations.
Method Chi-squared
Comments Without any adjustment for covariates
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.38 to -0.11
Estimation Comments Estimated Value is the between-group difference in change from BL
7.Post-Hoc Outcome
Title Change From Baseline (BL) Anterior Chamber (AC) Cells at Day 15
Hide Description

The difference in mean changes from BL in AC cell count grade at Day 15 for KPI-121 1% dosed twice daily (BID) compared with vehicle dosed BID.

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 1 (Baseline) and Visit 6 (Day 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat - All subjects randomized
Arm/Group Title KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Hide Arm/Group Description:
KPI-121 1% Ophthalmic Suspension dosed BID
Vehicle of KPI-121 1% Ophthalmic Suspension dosed BID
Overall Number of Participants Analyzed 257 254
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.8  (0.84) -1.6  (0.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KPI-121 1% Ophthalmic Suspension, Vehicle of KPI-121 1% Ophthalmic Suspension
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0169
Comments P-values have no inferential value for post hoc evaluations.
Method Chi-squared
Comments Without adjustments for any covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.28 to -0.03
Estimation Comments Estimated Value is the between-group difference for change from BL
Time Frame Adverse events were collected from the time a subjects signed the informed consent until they exited the study at the end of Visit 7 (up to 18 days).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Hide Arm/Group Description KPI-121 1% Ophthalmic Suspension dosed BID Vehicle of KPI-121 1% Ophthalmic Suspension dosed BID
All-Cause Mortality
KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Affected / at Risk (%) Affected / at Risk (%)
Total   0/261 (0.00%)      0/259 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/261 (0.38%)      2/259 (0.77%)    
Cardiac disorders     
Angina pectoris  1  0/261 (0.00%)  0 1/259 (0.39%)  1
Hepatobiliary disorders     
Cholecystitis  1  1/261 (0.38%)  1 0/259 (0.00%)  0
Nervous system disorders     
erebrovascular Accident  1  0/261 (0.00%)  0 1/259 (0.39%)  1
Vascular disorders     
Hypertensive emergency  1  0/261 (0.00%)  0 1/259 (0.39%)  1
1
Term from vocabulary, MedDRA (16.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
KPI-121 1% Ophthalmic Suspension Vehicle of KPI-121 1% Ophthalmic Suspension
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/261 (6.90%)      21/259 (8.11%)    
Eye disorders     
Cystoid macular oedema  1  3/261 (1.15%)  3 3/259 (1.16%)  4
Eye pain  1  3/261 (1.15%)  3 6/259 (2.32%)  6
Posterior capsule opacification  1  3/261 (1.15%)  3 4/259 (1.54%)  4
General disorders     
Instilation site pain  1  1/261 (0.38%)  2 3/259 (1.16%)  4
Infections and infestations     
Nasopharyngitis  1  4/261 (1.53%)  4 1/259 (0.39%)  1
Nervous system disorders     
Headache  1  4/261 (1.53%)  4 4/259 (1.54%)  4
1
Term from vocabulary, MedDRA (16.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
No submission for publication or public disclosure will be made by the PI until after the publication of the results of the multi-center clinical trial by the Sponsor. Thereafter, PI shall provide KALA with an advance copy of any proposed publication or public disclosure at least sixty (60) days prior to the planned date of submission or disclosure and KALA shall have forty-five (45) days from the date of its receipt to recommend changes.
Results Point of Contact
Name/Title: Head, Clinical Operations
Organization: Kala Pharmaceuticals, Inc.
Phone: 781-996-5252
Responsible Party: Kala Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02793817     History of Changes
Other Study ID Numbers: KPI-121-C-005
First Submitted: June 3, 2016
First Posted: June 8, 2016
Results First Submitted: October 25, 2018
Results First Posted: April 17, 2019
Last Update Posted: April 17, 2019