Trial Outcomes & Findings for Safety and Efficacy of KPI-121 Compared to Placebo in Subjects With Dry Eye Disease (NCT NCT02819284)

NCT ID: NCT02819284

Last Updated: 2021-01-05

Results Overview

Comparison of mean change from baseline for 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

909 participants

Primary outcome timeframe

Baseline/Visit 2 (Day 1) - Visit 4 (Day 15)

Results posted on

2021-01-05

Participant Flow

909 subjects were randomized, 4 of which were not included in any analysis population as agreed upon with the FDA. 3 individuals had participated in more than one study therefore the data for their second-participation were not included and 1 individual did not receive treatment.

Participant milestones

Participant milestones
Measure	KPI-121 0.25% Ophthalmic Suspension Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Overall Study STARTED	452	453
Overall Study COMPLETED	447	448
Overall Study NOT COMPLETED	5	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of KPI-121 Compared to Placebo in Subjects With Dry Eye Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KPI-121 0.25% Ophthalmic Suspension n=452 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=453 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension	Total n=905 Participants Total of all reporting groups
Age, Continuous	59.1 years STANDARD_DEVIATION 14.48 • n=5 Participants	59.3 years STANDARD_DEVIATION 15.01 • n=7 Participants	59.2 years STANDARD_DEVIATION 14.74 • n=5 Participants
Sex: Female, Male Female	332 Participants n=5 Participants	354 Participants n=7 Participants	686 Participants n=5 Participants
Sex: Female, Male Male	120 Participants n=5 Participants	99 Participants n=7 Participants	219 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	39 Participants n=5 Participants	35 Participants n=7 Participants	74 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	58 Participants n=5 Participants	54 Participants n=7 Participants	112 Participants n=5 Participants
Race (NIH/OMB) White	345 Participants n=5 Participants	352 Participants n=7 Participants	697 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	452 participants n=5 Participants	453 participants n=7 Participants	905 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 4 (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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=446 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=447 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15)	-0.3812 score on a scale Standard Deviation 0.60560	-0.2371 score on a scale Standard Deviation 0.62256

PRIMARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 4 (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.

Comparison of mean 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=445 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=444 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15)	-11.14 score on a scale Standard Deviation 19.901	-9.24 score on a scale Standard Deviation 17.002

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 4 (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.

Proportion of subjects with ≥1 improvement from baseline in conjunctival hyperemia scores in the study eye. 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=446 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=447 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Proportion of Subjects With ≥ 1 Unit Improvement From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia Worst Region at Visit 4 (Day 15)	171 Participants	127 Participants

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 3 (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.

Comparison of ocular discomfort scores 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 using 3-day mean scores.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=449 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=451 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/ Visit 2 (Day 1) in Ocular Discomfort Severity Scores at Visit 3 (Day 8)	-6.92 score on a scale Standard Deviation 15.541	-4.86 score on a scale Standard Deviation 14.911

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Day 4

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.

Comparison of mean 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=447 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=449 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Week 2 (Day 1) in Ocular Discomfort Scores to Day 4	-5.09 score on a scale Standard Deviation 14.523	-4.10 score on a scale Standard Deviation 14.894

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 4 (Day 15)

Population: Sub-group of Intent to Treat population with more severe ocular discomfort minus subjects in each treatment group that discontinued the study by this time point or otherwise did not have this assessment completed.

Comparison of mean 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, in a sub-group of participants with more severe ocular discomfort at baseline, using 3 day means.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=254 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=257 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Week 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) in a Subgroup	-12.45 score on a scale Standard Deviation 20.352	-9.45 score on a scale Standard Deviation 17.489

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Day 3

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.

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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=451 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=449 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity Scores at Day 3 (Diary)	-3.28 score on a scale Standard Deviation 13.697	-3.15 score on a scale Standard Deviation 14.126

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 4 (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.

Comparison of mean eye dryness 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=447 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=445 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Eye Dryness Scores at Visit 4 (Day 15)	-14.0 score on a scale Standard Deviation 22.78	-11.5 score on a scale Standard Deviation 20.53

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 3 (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.

Comparison of mean eye dryness 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=442 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=447 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Eye Dryness Scores at Visit 3 (Day 8)	-9.6 score on a scale Standard Deviation 18.66	-8.0 score on a scale Standard Deviation 18.94

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Day 1

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.

Comparison of mean 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=451 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=447 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Ocular Discomfort Severity Scores on Day 2 (Diary) Minus Baseline/Visit 2 (Day 1)	-2.33 score on a scale Standard Deviation 13.707	-2.43 score on a scale Standard Deviation 13.364

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 4 (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.

Comparison of mean ocular discomfort frequency 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=445 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=444 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Frequency Scores at Visit 4 (Day 15)	-10.20 score on a scale Standard Deviation 20.722	-8.38 score on a scale Standard Deviation 17.974

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 3 (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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=449 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=451 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Subject-rated Ocular Discomfort Frequency Scores at Visit 3 (Day 8)	-5.96 score on a scale Standard Deviation 16.133	-4.42 score on a scale Standard Deviation 16.133

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 4 (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.

Comparison of mean corneal fluorescein staining 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=448 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=448 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Inferior Corneal Fluorescein Staining Score at Visit 4 (Day 15)	-0.6 score on a scale Standard Deviation 0.86	-0.5 score on a scale Standard Deviation 0.83

SECONDARY outcome

Timeframe: Baseline/Visit 2 (Day 1) - Visit 4 (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.

Comparison of mean nasal corneal fluorescein staining 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.

Outcome measures

Outcome measures
Measure	KPI-121 0.25% Ophthalmic Suspension n=448 Participants Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=448 Participants Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Change From Baseline/Visit 2 (Day 1) in Nasal Corneal Fluorescein Staining Score at Visit 4 (Day 15)	-0.6 score on a scale Standard Deviation 0.86	-0.4 score on a scale Standard Deviation 0.83

Adverse Events

KPI-121 0.25% Ophthalmic Suspension

Serious events: 3 serious events

Other events: 57 other events

Deaths: 0 deaths

Vehicle of KPI-121 0.25% Ophthalmic Suspension

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	KPI-121 0.25% Ophthalmic Suspension n=452 participants at risk Participants randomized to KPI-121 0.25% Ophthalmic Suspension	Vehicle of KPI-121 0.25% Ophthalmic Suspension n=453 participants at risk Participants randomized to Vehicle of KPI-121 0.25% Ophthalmic Suspension
Gastrointestinal disorders diverticulum intestinal	0.22% 1/452 • Number of events 1 • Adverse events were collected from Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15). Both treatment-related and non-treatment-related adverse events are reported here.	0.00% 0/453 • Adverse events were collected from Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15). Both treatment-related and non-treatment-related adverse events are reported here.
Musculoskeletal and connective tissue disorders hip fracture	0.22% 1/452 • Number of events 1 • Adverse events were collected from Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15). Both treatment-related and non-treatment-related adverse events are reported here.	0.00% 0/453 • Adverse events were collected from Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15). Both treatment-related and non-treatment-related adverse events are reported here.
Musculoskeletal and connective tissue disorders intervertebral disc protrusion	0.22% 1/452 • Number of events 1 • Adverse events were collected from Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15). Both treatment-related and non-treatment-related adverse events are reported here.	0.00% 0/453 • Adverse events were collected from Visit 2 (Day 1) until they exited the study at Visit 4 (Day 15). Both treatment-related and non-treatment-related adverse events are reported here.

Other adverse events

Additional Information

VP Clinical Development

Kala Pharmaceuticals, Inc.

Phone: (781) 996-5252

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The agreement between the Principal Investigator and the Sponsor restricts the PI's rights to discuss or publish trial results until after the first to occur of the following: (a) publication of such multi-center clinical trial results; (b) notification by sponsor that such a multi-center clinical trial submission is no longer planned; or ( c) the eighteen ( 18) month anniversary of the completion, abandonment or termination of such multi-center clinical trial.
Publication restrictions are in place

Restriction type: OTHER