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)

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00926185
• Collaborator: (none)
• Enrollment: 230
• Locations: 5
• Arms: 4
• Actual Duration (Months): 6.5
• Patients Per Site: 46
• Patients Per Site Per Month: 7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of three different concentrations (0.1%, 1.0%, 5.0%) of SAR 1118 Ophthalmic Solution compared to placebo in the treatment of dry eye.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye	Drug: Lifitegrast; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 230 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Double-Masked and Placebo-Controlled Study Evaluating the Efficacy of Three Different Concentrations (0.1%, 1.0%, 5.0%) of SAR 1118 Ophthalmic Solution in Subjects With Dry Eye Using the Controlled Adverse Environment (CAE) Model
• Actual Study Start Date: Aug 3, 2009
• Actual Primary Completion Date: Feb 18, 2010
• Actual Study Completion Date: Feb 18, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo Ophthalmic Solution	Drug: Placebo; Ophthalmic Solution
Experimental: 0.1% Lifitegrast Lifitegrast	Drug: Lifitegrast; Ophthalmic Solution; Other Names: SAR 1118
Experimental: 1.0% Lifitegrast Lifitegrast	Drug: Lifitegrast; Ophthalmic Solution; Other Names: SAR 1118
Experimental: 5.0% Lifitegrast Lifitegrast	Drug: Lifitegrast; Ophthalmic Solution; Other Names: SAR 1118

Outcome Measures

Primary Outcome Measures

1. Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84 [Day 84]

   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.

Secondary Outcome Measures

1. Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84 [Baseline (Day 0) and Day 84]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed Informed Consent Form and HIPAA document

• Willing and able to comply with all study procedures

• Be at least 18 years of age

• Patient-reported history of dry eye in both eyes

• Demonstrate a positive response when exposed to the Controlled Adverse Environment model

• A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period

Exclusion Criteria:

• Any ocular condition that, in the opinion of the Investigator, could affect study parameters including, but not limited to, active ocular infection, ocular inflammation, glaucoma, and/or diabetic retinopathy

• Unwilling to avoid wearing contact lenses for 7 days prior to and for duration of the study period

• Any blood donation or significant loss of blood within 56 days of Visit 1

• Any history of immunodeficiency disorder, positive HIV, hepatitis B, C, or evidence of acute active hepatitis A (anti-HAV IgM), or organ or bone marrow transplant.

• Use of any topical ophthalmic preparations (including tear substitutes) 72 hrs prior to screening assessments and through the entire study period

• Any significant illness that could interfere with study parameters

• History of laser-assisted in situ keratomileusis (LASIK) or similar type of corneal refractive surgery within 12 months prior to Visit 1, and/or any other ocular surgical procedure within 12 months prior to Visit 1; or any scheduled ocular surgical procedure during the study period.

• Known history of alcohol and/or drug abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Eye Care Group	Waterbury	Connecticut	United States	06708
2	Central Maine Eye Care	Lewiston	Maine	United States	04243
3	Ora, Inc. (two locations)	Andover	Massachusetts	United States	01840
4	Mundorf Eye Center	Charlotte	North Carolina	United States	28204
5	Total Eye Care, P.A.	Memphis	Tennessee	United States	38119

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00926185
• Other Study ID Numbers: 1118-KCS-100
• First Posted: Jun 23, 2009
• Last Update Posted: Aug 9, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Shire: Dry Eye; ophthalmic delivery
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Lifitegrast

Study Results

Participant Flow

Pre-assignment Detail	The study was conducted in a Controlled Adverse Environment (CAE).

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	57	57	58	58
COMPLETED	54	51	48	48
NOT COMPLETED	3	6	10	10

Baseline Characteristics

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	57	57	58	58	230
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.14 (13.100)	63.63 (11.883)	62.26 (12.220)	60.38 (12.930)	62.34 (12.523)
Sex: Female, Male (Count of Participants)
Female	47 82.5%	40 70.2%	47 81%	45 77.6%	179 77.8%
Male	10 17.5%	17 29.8%	11 19%	13 22.4%	51 22.2%

Outcome Measures

1. Primary Outcome

Title	Inferior Corneal Fluorescein Staining Score in Pre-Controlled Adverse Environment at Day 84
Description	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.
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Measure Participants	57	55	54	55
Mean (Standard Deviation) [units on a scale]	2.03 (0.868)	1.92 (0.768)	1.83 (0.680)	2.05 (0.715)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 0.1%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9381
	Comments
	Method	Dunnett's test
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis of covariance model with treatment, baseline, and site.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 1.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3585
	Comments
	Method	Dunnett's test
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis of covariance model with treatment, baseline, and site.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 5.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1375
	Comments
	Method	Dunnett's test
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis of covariance model with treatment, baseline, and site.

2. Secondary Outcome

Title	Inferior Corneal Staining Score Change From Baseline (CFB) to Day 84
Description	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.
Time Frame	Baseline (Day 0) and Day 84

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Measure Participants	57	57	58	58
Pre-CAE: Baseline	1.78 (0.473)	1.82 (0.508)	1.77 (0.515)	1.65 (0.513)
Pre-CAE: CFB to Day 84	0.25 (0.841)	0.10 (0.735)	0.05 (0.773)	0.40 (0.802)
Post-CAE: Baseline	3.18 (0.417)	3.28 (0.610)	3.16 (0.523)	3.04 (0.602)
Post-CAE: Day 84	2.86 (0.962)	2.88 (0.860)	2.90 (0.918)	2.62 (0.855)

Adverse Events

Time Frame	From the first dose of study drug until the end of follow-up visit, up to Day 86
Arm/Group Title	Lifitegrast 0.1%		Lifitegrast 1.0%		Lifitegrast 5.0%		Placebo
Arm/Group Description
All Cause Mortality
	Lifitegrast 0.1%		Lifitegrast 1.0%		Lifitegrast 5.0%		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lifitegrast 0.1%		Lifitegrast 1.0%		Lifitegrast 5.0%		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/57 (3.5%)		1/57 (1.8%)		0/58 (0%)		1/58 (1.7%)
Cardiac disorders
Cardiac arrest	0/57 (0%)	0	1/57 (1.8%)	1	0/58 (0%)	0	0/58 (0%)	0
Injury, poisoning and procedural complications
Hip fracture	1/57 (1.8%)	1	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0
Investigations
Oxygen saturation decreased	1/57 (1.8%)	1	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/57 (0%)	0	0/57 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Lifitegrast 0.1%		Lifitegrast 1.0%		Lifitegrast 5.0%		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/57 (35.1%)		13/57 (22.8%)		40/58 (69%)		11/58 (19%)
Eye disorders
Conjunctival haemorrhage	0/57 (0%)	0	2/57 (3.5%)	3	3/58 (5.2%)	3	0/58 (0%)	0
Visual acuity reduced	6/57 (10.5%)	7	2/57 (3.5%)	3	1/58 (1.7%)	1	3/58 (5.2%)	3
General disorders
Instillation site irritation	7/57 (12.3%)	7	5/57 (8.8%)	5	20/58 (34.5%)	20	6/58 (10.3%)	6
Instillation site pain	6/57 (10.5%)	6	3/57 (5.3%)	3	20/58 (34.5%)	20	3/58 (5.2%)	3
Instillation site reaction	0/57 (0%)	0	1/57 (1.8%)	2	8/58 (13.8%)	16	0/58 (0%)	0
Nervous system disorders
Dysgeusia	1/57 (1.8%)	1	2/57 (3.5%)	3	7/58 (12.1%)	12	0/58 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.