A Study to Evaluate Efficacy and Safety of Lifitegrast in Subjects With Dry Eye (OPUS-3)

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02284516
• Collaborator: (none)
• Enrollment: 711
• Locations: 41
• Arms: 2
• Actual Duration (Months): 10.9
• Patients Per Site: 17.3
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

Evaluate the efficacy and safety of Lifitegrast in subjects with dry eye disease and a recent history of artificial tear use.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Disease	Drug: Lifitegrast; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 711 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-masked, and Placebo-controlled Study Evaluating the Efficacy and Safety of a 5.0% Concentration of Lifitegrast Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease and History of Recent Artificial Tear Use
• Actual Study Start Date: Nov 6, 2014
• Actual Primary Completion Date: Oct 5, 2015
• Actual Study Completion Date: Oct 5, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lifitegrast Lifitegrast Ophthalmic Solution 5%, BID for 84 days	Drug: Lifitegrast; Lifitegrast Ophthalmic Solution 5%, BID for 84 days
Placebo Comparator: Placebo Placebo to match active treatment, BID for 84 days	Drug: Placebo; Placebo to match active treatment, BID for 84 days

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Patient-Reported Eye Dryness Score to Day 84 [Baseline to Day 84]

   Eye dryness score was scored on a Visual Analogue Scale (VAS) ranges from 0-100 (0=no discomfort; 100=maximal discomfort).

Secondary Outcome Measures

1. Change From Baseline in Patient-Reported Eye Dryness Score to Day 14 and Day 42 [Baseline to Day 14 and Day 42]

   Eye dryness score was scored on a Visual Analogue Scale (VAS) ranges from 0-100 (0=no discomfort; 100=maximal discomfort).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient-reported history of Dry Eye Disease in both eyes.

• Use of over the counter artificial tears within the past 30 days.

• A negative urine pregnancy test for females and willingness to use adequate birth control throughout the study.

• Able and willing to comply with all study procedures.

Exclusion Criteria:

• Presence of an ocular condition that could affect the study parameters such as active ocular infections, ocular inflammation, glaucoma, or diabetic retinopathy;.

• Unwilling to stop wearing contact lenses during the study.

• LASIK or other ocular surgical procedures within 12 months prior to or during the study.

• Use of prohibited medications

• Significant medical conditions that could affect the study parameters.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham, UAB School of Optometry	Birmingham	Alabama	United States	35294
2	Arizona Eye Center	Chandler	Arizona	United States	85225
3	Sall Research Medical Center	Artesia	California	United States	90701
4	United Medical Research Institute	Inglewood	California	United States	90301
5	North Valley Eye Medical Group, Inc	Mission Hills	California	United States	91345
6	Montebello Medical Eye Center, Inc.	Montebello	California	United States	90640
7	Eye Research Foundation	Newport Beach	California	United States	92663
8	Arch Health Partners	Poway	California	United States	92064
9	Martel Eye Medical Group	Rancho Cordova	California	United States	95670
10	Shasta Eye Medical Group, Inc.	Redding	California	United States	96001
11	West Coast Eye Care Associates	San Diego	California	United States	92115
12	Chicago Cornea Consultants, Ltd.	Hoffman Estates	Illinois	United States	60169
13	Jackson Eye, SC	Lake Villa	Illinois	United States	60046
14	Price Vision Group	Indianapolis	Indiana	United States	46260
15	John-Kenyon American Eye Institute	New Albany	Indiana	United States	47150
16	Koffler Vision Group	Lexington	Kentucky	United States	40509
17	The Eye Care Institute	Louisville	Kentucky	United States	40206
18	Holpro Vision, Ltd.	Union	Kentucky	United States	41091
19	Clinical Eye Research of Boston	Winchester	Massachusetts	United States	01890
20	Lifelong Vision Foundation	Chesterfield	Missouri	United States	63017
21	Tauber Eye Center	Kansas City	Missouri	United States	64111
22	Tekwani Vision Center	Saint Louis	Missouri	United States	63128
23	Ophthalmology Consultants, Ltd.	Saint Louis	Missouri	United States	63131
24	Comprehensive Eye Care, Ltd.	Washington	Missouri	United States	63090
25	Wellish Vision Institute	Las Vegas	Nevada	United States	89119
26	Abrams Eye Institute	Las Vegas	Nevada	United States	89148
27	Clinical Vision Research Center at SUNY	New York	New York	United States	10036
28	Ophthalmic Consultants Of Long Island	Rockville Centre	New York	United States	11570
29	South Shore Eye Care, LLP	Wantagh	New York	United States	11793
30	Abrams Eye Center	Cleveland	Ohio	United States	44115
31	Scott & Christie and Associates, PC	Cranberry Township	Pennsylvania	United States	16066
32	Matossian Eye Associates	Doylestown	Pennsylvania	United States	18902
33	Toyos Clinic	Nashville	Tennessee	United States	37203
34	The Cataract & Glaucoma Center	El Paso	Texas	United States	79902
35	Advanced Laser Vision and Surgical Institute	Houston	Texas	United States	77034
36	Whitsett Vision Group	Houston	Texas	United States	77056
37	University of Houston College of Optometry	Houston	Texas	United States	77204
38	The Eye Clinic of Texas (Houston Eye Associates)	League City	Texas	United States	77573
39	Eye Clinics of South Texas, P.A.	San Antonio	Texas	United States	78209
40	R and R Eye Research, LLC.	San Antonio	Texas	United States	78229
41	See Clearly Vision	McLean	Virginia	United States	22012

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: NCT02284516
• Other Study ID Numbers: SHP606-304
• First Posted: Nov 6, 2014
• Last Update Posted: Jun 11, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Lifitegrast

Study Results

Participant Flow

Pre-assignment Detail	Two participants from placebo arm (N=356) has taken study drug by mistake and considered for "Lifitegrast" arm (N=355). Therefore, Placebo (N=354), Lifitegrast (N=357) were considered for safety analysis.

Arm/Group Title	Placebo	Lifitegrast
Arm/Group Description	Placebo ophthalmic solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.	Lifitegrast 5% Ophthalmic Solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.
Period Title: Overall Study
STARTED	356	355
Safety Population	354	357
COMPLETED	318	319
NOT COMPLETED	38	36

Baseline Characteristics

Arm/Group Title	Placebo	Lifitegrast	Total
Arm/Group Description	Placebo ophthalmic solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.	Lifitegrast 5% Ophthalmic Solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.	Total of all reporting groups
Overall Participants	356	355	711
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.6 (14.84)	58.8 (14.10)	58.7 (14.47)
Sex: Female, Male (Count of Participants)
Female	269 75.6%	268 75.5%	537 75.5%
Male	87 24.4%	87 24.5%	174 24.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Patient-Reported Eye Dryness Score to Day 84
Description	Eye dryness score was scored on a Visual Analogue Scale (VAS) ranges from 0-100 (0=no discomfort; 100=maximal discomfort).
Time Frame	Baseline to Day 84

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population included all randomized participants who took at least 1 dose of investigational product with last observation carried forward (LOCF). Here, n = number of participants analyzed for the specific categories of each arm, respectively.

Arm/Group Title	Placebo	Lifitegrast
Arm/Group Description	Placebo ophthalmic solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.	Lifitegrast 5% Ophthalmic Solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.
Measure Participants	356	355
Baseline (n=356, 355)	69.0 (17.08)	68.3 (16.88)
Change from Baseline to Day 84 (n=353, 353)	-30.7 (28.01)	-37.9 (28.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lifitegrast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	=0.0007
	Comments	The primary analysis was performed using a stratified 2-sample t-test (that is, analysis of variance [ANOVA]).
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	7.16
	Confidence Interval	(2-Sided) 95%; 3.04 to 11.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.096
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Patient-Reported Eye Dryness Score to Day 14 and Day 42
Description	Eye dryness score was scored on a Visual Analogue Scale (VAS) ranges from 0-100 (0=no discomfort; 100=maximal discomfort).
Time Frame	Baseline to Day 14 and Day 42

Outcome Measure Data

Analysis Population Description

ITT population with LOCF. Here, n = number of participants analyzed for the specific categories of each arm, respectively.

Arm/Group Title	Placebo	Lifitegrast
Arm/Group Description	Placebo ophthalmic solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.	Lifitegrast 5% Ophthalmic Solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.
Measure Participants	356	355
Baseline (n=356, 355)	69.0 (17.08)	68.3 (16.88)
Change from Baseline to Day 14 (n=353, 352)	-15.0 (22.40)	-22.9 (25.44)
Change from Baseline to Day 42 (n=353, 353)	-23.9 (25.99)	-33.2 (27.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lifitegrast
	Comments	Baseline and Day 14
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary analysis was performed using a stratified 2-sample t-test (that is, analysis of variance [ANOVA]).
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	7.85
	Confidence Interval	(2-Sided) 95%; 4.33 to 11.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.792
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lifitegrast
	Comments	Baseline and Day 42
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The primary analysis was performed using a stratified 2-sample t-test (that is, analysis of variance [ANOVA]).
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	9.32
	Confidence Interval	(2-Sided) 95%; 5.44 to 13.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.976
	Estimation Comments

Adverse Events

Time Frame	From start of the study drug administration upto Day 91 or Early termination (ET)
Adverse Event Reporting Description	Two participants from placebo arm (N=356) has taken study drug by mistake and considered for "Lifitegrast" arm (N=355). Therefore, Placebo (N=354), Lifitegrast (N=357) were considered for safety analysis.
Arm/Group Title	Placebo		Lifitegrast
Arm/Group Description	Placebo ophthalmic solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.		Lifitegrast 5% Ophthalmic Solution was administered to the ocular surface as a single eye drop twice daily in both eyes for 84 days.
All Cause Mortality
	Placebo		Lifitegrast
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Lifitegrast
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/354 (1.1%)		4/357 (1.1%)
Infections and infestations
Pneumonia	0/354 (0%)	0	1/357 (0.3%)	1
Injury, poisoning and procedural complications
Periprosthetic fracture	1/354 (0.3%)	1	0/357 (0%)	0
Musculoskeletal and connective tissue disorders
Lower limb fracture	1/354 (0.3%)	1	0/357 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/354 (0.3%)	1	0/357 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/354 (0%)	0	1/357 (0.3%)	1
Transient ischaemic attack	0/354 (0%)	0	1/357 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Lung neoplasm malignant	0/354 (0%)	0	1/357 (0.3%)	1
Vascular disorders
Accelerated hypertension	1/354 (0.3%)	1	0/357 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Lifitegrast
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/354 (8.5%)		107/357 (30%)
General disorders
Instillation site irritation	11/354 (3.1%)	12	65/357 (18.2%)	68
Instillation site reaction	19/354 (5.4%)	21	45/357 (12.6%)	51
Nervous system disorders
Dysgeusia	1/354 (0.3%)	1	46/357 (12.9%)	46

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If a multicenter 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 multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.