Effects of Xiidra on Closed Eye Tear Film Leukocytes in Dry Eye Disease

Every night during sleep, there is an accumulation of white blood cells in the closed eye. The closed eye white blood cells are predominantly neutrophils, but there is a small population (3%) of T cells. The effects of these closed eye white blood cells on dry eye disease pathogenesis have yet to be fully elucidated, but preliminary evidence suggests that closed eye neutrophils may have an associated hyperactivity and increased degranulation in dry eye disease that could contribute to epithelial instability. As an anti-T cell therapy, Xiidra offers an opportunity to better understand how the closed eye white blood cells are recruited and activated. This study also seeks to verify the proposed mechanism of action.

Study Overview

• Status: Withdrawn
• Conditions: Ocular Inflammation; Dry Eye; Keratoconjunctivitis Sicca; Contact Lens Complication; Ocular Discomfort
• Intervention / Treatment: Drug: Lifitegrast

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to understand and sign an informed consent and HIPAA privacy document
• Greater than 18 years of age at time of informed consent
• Able and willing to follow protocol instructions
• Capable of performing at-home eye wash
• Must be willing to drop off samples and comply with study visit procedures
• For contact lens wearers, must wear lenses at least four hours per day, four days per week

Exclusion Criteria:

• Current cigarette smokers
• Current participation in any investigational drug or device study. If subjects choose to participate in another investigational drug or device study, they will be discontinued from this study protocol.
• Current pregnancy or nursing as indicated by self-report. While not a safety issue, pregnancy or nursing influences the biochemical composition of the tear film.
• Any systemic health conditions that alter tear film physiology
• A history of ocular surgery within the past 12 months
• Any active ocular infection or inflammation
• Any present use of Accutane or ocular medications
• Any history of significant adverse reaction to lifitegrast or other components of the drug product, or contraindication to the use of lifitegrast or other components of the drug product
• Any prior exposure to lifitegrast.
• For normal and dry eye subjects, any history of contact lens wear within the past three months.
• For contact lens wearers, any change of soft contact lens brand or care solutions within 30 days prior to screening or any anticipation of changing current type/brand of contact lenses or care solutions throughout the 84 day study
• Any condition, which in the examiner's opinion, may put the subject at significant risk, confound study results, or interfere with their participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal, asymptomatic non-lens wearers; Lifitegrast ophthalmic solution, 5.0%. Dosage: 1 drop in each eye, twice daily: once in the morning and once before bed.	Drug: Lifitegrast; Lifitegrast ophthalmic solution, 5.0%. 1 drop instilled into each eye once in the morning and once before bed.; Other Names: Xiidra
Experimental: Dry eye subjects, non-lens wearers; Lifitegrast ophthalmic solution, 5.0%. Dosage: 1 drop in each eye, twice daily: once in the morning and once before bed.	Drug: Lifitegrast; Lifitegrast ophthalmic solution, 5.0%. 1 drop instilled into each eye once in the morning and once before bed.; Other Names: Xiidra
Experimental: Contact lens wearers with discomfort; Lifitegrast ophthalmic solution, 5.0%. Dosage: 1 drop in each eye, twice daily: once in the morning and once before bed.	Drug: Lifitegrast; Lifitegrast ophthalmic solution, 5.0%. 1 drop instilled into each eye once in the morning and once before bed.; Other Names: Xiidra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the total number of T cells recovered from the closed eye to day 84	Subjects will be trained and required to collect their closed eye tears at home, using a gentle saline rinse of the ocular surface. Enumeration of recovered T cells will be performed by flow cytometry.	Baseline to day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the total number of neutrophils recovered from the closed eye to day 84.	Subjects will be trained and required to collect their closed eye tears at home, using a gentle saline rinse of the ocular surface. Enumeration of recovered neutrophils will be performed by flow cytometry.	Baseline to day 84.

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Shire
• Investigators: Principal Investigator: Kelly K Nichols, OD MPH PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Actual): January 30, 2019
• Study Completion (Actual): January 30, 2019

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: T cell; neutrophil; dry eye disease; contact lens discomfort; lifitegrast; ocular surface homeostasis
• Additional Relevant MeSH Terms: Pathologic Processes; Lacrimal Apparatus Diseases; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Inflammation; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratoconjunctivitis; Pharmaceutical Solutions; Ophthalmic Solutions; Lifitegrast
• Other Study ID Numbers: 300001139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No