Trial Outcomes & Findings for A Study Evaluating the Efficacy of SAR 1118 (0.1%, 1.0%, 5.0%) Ophthalmic Solution in Subjects With Dry Eye Conducted in a Controlled Adverse Environment (CAE) (NCT NCT00926185)

Results Overview

Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The staining was graded with the Ophthalmic Research Associates, Inc. (ORA) scale. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=occasional; 2=countable; 3=uncountable, but not confluent; 4=confluent) with 0.5 point increments, and lower score indicates a better outcome. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

230 participants

Primary outcome timeframe

Day 84

Results posted on

2021-08-09

Participant Flow

The study was conducted in a Controlled Adverse Environment (CAE).

Participant milestones

Participant milestones
Measure	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Overall Study STARTED	57	57	58	58
Overall Study COMPLETED	54	51	48	48
Overall Study NOT COMPLETED	3	6	10	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study Evaluating the Efficacy of SAR 1118 (0.1%, 1.0%, 5.0%) Ophthalmic Solution in Subjects With Dry Eye Conducted in a Controlled Adverse Environment (CAE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lifitegrast 0.1% n=57 Participants	Lifitegrast 1.0% n=57 Participants	Lifitegrast 5.0% n=58 Participants	Placebo n=58 Participants	Total n=230 Participants Total of all reporting groups
Age, Continuous	63.14 years STANDARD_DEVIATION 13.100 • n=5 Participants	63.63 years STANDARD_DEVIATION 11.883 • n=7 Participants	62.26 years STANDARD_DEVIATION 12.220 • n=5 Participants	60.38 years STANDARD_DEVIATION 12.930 • n=4 Participants	62.34 years STANDARD_DEVIATION 12.523 • n=21 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	40 Participants n=7 Participants	47 Participants n=5 Participants	45 Participants n=4 Participants	179 Participants n=21 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	17 Participants n=7 Participants	11 Participants n=5 Participants	13 Participants n=4 Participants	51 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 84

Population: Intent-to-treat (ITT) population with LOCF defined as all randomized subjects. For the efficacy analysis, the Last Observation Carried Forward (LOCF) method will be used to impute missing values.

Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The staining was graded with the Ophthalmic Research Associates, Inc. (ORA) scale. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=occasional; 2=countable; 3=uncountable, but not confluent; 4=confluent) with 0.5 point increments, and lower score indicates a better outcome. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline.

Outcome measures

Outcome measures
Measure	Lifitegrast 0.1% n=57 Participants	Lifitegrast 1.0% n=55 Participants	Lifitegrast 5.0% n=54 Participants	Placebo n=55 Participants
Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84	2.03 units on a scale Standard Deviation 0.868	1.92 units on a scale Standard Deviation 0.768	1.83 units on a scale Standard Deviation 0.680	2.05 units on a scale Standard Deviation 0.715

SECONDARY outcome

Timeframe: Baseline (Day 0) and Day 84

Population: ITT set with LOCF was used for analysis of this outcome. Here, "n" signifies the number of participants evaluable for the respective time points.

Corneal staining was performed to grade the degree of corneal epithelial cell injury as measured by fluorescence using slit-lamp examination. The staining was graded with the Ophthalmic Research Associates, Inc. (ORA) scale. The corneal surface is divided into three regions: superior, central and inferior. The scores for each of these 3 regions ranged from 0 to 4 (0=no staining; 1=occasional; 2=countable; 3=uncountable, but not confluent; 4=confluent) with 0.5 point increments, and lower score indicates a better outcome. Inferior corneal fluorescein staining scores from the study eye only were reported. Study eye is the 'worse eye', defined as the eye with worse (higher) score at baseline.

Outcome measures

Outcome measures
Measure	Lifitegrast 0.1% n=57 Participants	Lifitegrast 1.0% n=57 Participants	Lifitegrast 5.0% n=58 Participants	Placebo n=58 Participants
Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 Pre-CAE: Baseline	1.78 units on a scale Standard Deviation 0.473	1.82 units on a scale Standard Deviation 0.508	1.77 units on a scale Standard Deviation 0.515	1.65 units on a scale Standard Deviation 0.513
Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 Pre-CAE: CFB to Day 84	0.25 units on a scale Standard Deviation 0.841	0.10 units on a scale Standard Deviation 0.735	0.05 units on a scale Standard Deviation 0.773	0.40 units on a scale Standard Deviation 0.802
Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 Post-CAE: Baseline	3.18 units on a scale Standard Deviation 0.417	3.28 units on a scale Standard Deviation 0.610	3.16 units on a scale Standard Deviation 0.523	3.04 units on a scale Standard Deviation 0.602
Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 Post-CAE: Day 84	2.86 units on a scale Standard Deviation 0.962	2.88 units on a scale Standard Deviation 0.860	2.90 units on a scale Standard Deviation 0.918	2.62 units on a scale Standard Deviation 0.855

Adverse Events

Lifitegrast 0.1%

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Lifitegrast 1.0%

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Lifitegrast 5.0%

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lifitegrast 0.1% n=57 participants at risk	Lifitegrast 1.0% n=57 participants at risk	Lifitegrast 5.0% n=58 participants at risk	Placebo n=58 participants at risk
Cardiac disorders Cardiac arrest	0.00% 0/57 • From the first dose of study drug until the end of follow-up visit, up to Day 86	1.8% 1/57 • Number of events 1 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86
Injury, poisoning and procedural complications Hip fracture	1.8% 1/57 • Number of events 1 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/57 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86
Investigations Oxygen saturation decreased	1.8% 1/57 • Number of events 1 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/57 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/57 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/57 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86	1.7% 1/58 • Number of events 1 • From the first dose of study drug until the end of follow-up visit, up to Day 86

Other adverse events

Other adverse events
Measure	Lifitegrast 0.1% n=57 participants at risk	Lifitegrast 1.0% n=57 participants at risk	Lifitegrast 5.0% n=58 participants at risk	Placebo n=58 participants at risk
Eye disorders Conjunctival haemorrhage	0.00% 0/57 • From the first dose of study drug until the end of follow-up visit, up to Day 86	3.5% 2/57 • Number of events 3 • From the first dose of study drug until the end of follow-up visit, up to Day 86	5.2% 3/58 • Number of events 3 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86
Eye disorders Visual acuity reduced	10.5% 6/57 • Number of events 7 • From the first dose of study drug until the end of follow-up visit, up to Day 86	3.5% 2/57 • Number of events 3 • From the first dose of study drug until the end of follow-up visit, up to Day 86	1.7% 1/58 • Number of events 1 • From the first dose of study drug until the end of follow-up visit, up to Day 86	5.2% 3/58 • Number of events 3 • From the first dose of study drug until the end of follow-up visit, up to Day 86
General disorders Instillation site irritation	12.3% 7/57 • Number of events 7 • From the first dose of study drug until the end of follow-up visit, up to Day 86	8.8% 5/57 • Number of events 5 • From the first dose of study drug until the end of follow-up visit, up to Day 86	34.5% 20/58 • Number of events 20 • From the first dose of study drug until the end of follow-up visit, up to Day 86	10.3% 6/58 • Number of events 6 • From the first dose of study drug until the end of follow-up visit, up to Day 86
General disorders Instillation site pain	10.5% 6/57 • Number of events 6 • From the first dose of study drug until the end of follow-up visit, up to Day 86	5.3% 3/57 • Number of events 3 • From the first dose of study drug until the end of follow-up visit, up to Day 86	34.5% 20/58 • Number of events 20 • From the first dose of study drug until the end of follow-up visit, up to Day 86	5.2% 3/58 • Number of events 3 • From the first dose of study drug until the end of follow-up visit, up to Day 86
General disorders Instillation site reaction	0.00% 0/57 • From the first dose of study drug until the end of follow-up visit, up to Day 86	1.8% 1/57 • Number of events 2 • From the first dose of study drug until the end of follow-up visit, up to Day 86	13.8% 8/58 • Number of events 16 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86
Nervous system disorders Dysgeusia	1.8% 1/57 • Number of events 1 • From the first dose of study drug until the end of follow-up visit, up to Day 86	3.5% 2/57 • Number of events 3 • From the first dose of study drug until the end of follow-up visit, up to Day 86	12.1% 7/58 • Number of events 12 • From the first dose of study drug until the end of follow-up visit, up to Day 86	0.00% 0/58 • From the first dose of study drug until the end of follow-up visit, up to Day 86

Additional Information

Study Director

Shire (Note: Lifitegrast was divested to Novartis in 2019)

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicentre publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicentre Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER