Dry Eye Disease, Keratoconjunctivitis Sicca
Conditions
Keywords
ophthalmic delivery, Dry Eye
Brief summary
The purpose of the study is to evaluate the efficacy of SAR 1118 Ophthalmic Solution (5.0%) compared to placebo in the treatment of Dry Eye. The safety and tolerability of SAR 1118 Ophthalmic Solution (5.0%) compared to placebo in subjects with dry eye when administered BID for 12 weeks will also be evaluated.
Interventions
DRUGLifitegrast
Dosage Form: Ophthalmic Solution Dosage: 5.0% Frequency: BID Duration: 12 weeks
DRUGPlacebo
Dosage Form: Ophthalmic Solution Frequency: BID Duration: 12 weeks
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to read, sign, and date the informed consent and HIPAA documents * 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 artificial tear substitutes) 72 hrs prior to Visit 1 and during the study * Any significant chronic 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 * Subjects with Dry eye secondary to scarring or destruction of conjunctival goblet cells (as with Vitamin A deficiency)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Sign: Change From Baseline in Inferior Corneal Fluorescein Staining to Day 84 | Baseline (Day 0) to 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/none; 1=occasional/trace; 2=countable/mild; 3=uncountable, but not confluent/moderate; 4=confluent/severe) 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. |
| Ocular Symptom: Change From Baseline in Visual-Related Subscale of the Symptom Functional Scale Score to Day 84 | Baseline (Day 0) to Day 84 | The symptom functional scale is a validated instrument for ocular surface diseases, measuring the ocular symptoms, vision-related function, and environmental triggers. The 12 items of the symptom functional scale questionnaire were graded on a scale of 0 (none of the time) to 4 (all of the time). The index consisted of 3 sub scales: symptoms (sensitivity to light, gritty sensation, pain, blurred vision, and poor vision \[Items 1-5\]), visual-related sub scale of the symptom functional scale (ability to read, drive at night, use a computer, watch television \[Items 6-9\]), and environmental triggers (windy conditions, low humidity, air conditioning \[Items 10-12\]). The symptom functional scale was scored on a scale of 0 to 100, with higher scores representing greater disability. Negative change from baseline indicates improvement. |
Countries
United States
Participant flow
Pre-assignment details
The study was conducted in a Controlled Adverse Environment (CAE).
Participants by arm
| Arm | Count |
|---|---|
| Lifitegrast 5.0% | 293 |
| Placebo | 295 |
| Total | 588 |
Baseline characteristics
| Characteristic | Lifitegrast 5.0% | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 12.21 | 61.1 years STANDARD_DEVIATION 11.77 | 60.6 years STANDARD_DEVIATION 11.99 |
| Sex: Female, Male Female | 229 Participants | 217 Participants | 446 Participants |
| Sex: Female, Male Male | 64 Participants | 78 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 160 / 293 | 40 / 295 |
| serious Total, serious adverse events | 5 / 293 | 2 / 295 |
Outcome results
Primary
Ocular Sign: Change From Baseline in Inferior Corneal Fluorescein Staining to 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/none; 1=occasional/trace; 2=countable/mild; 3=uncountable, but not confluent/moderate; 4=confluent/severe) 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) to Day 84
Population: Intent-to-Treat (ITT) population with Last Observation Carried Forward (LOCF) included all randomized participants who received at least 1 dose of investigational product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lifitegrast 5.0% | Ocular Sign: Change From Baseline in Inferior Corneal Fluorescein Staining to Day 84 | -0.07 units on a scale | Standard Deviation 0.868 |
| Placebo | Ocular Sign: Change From Baseline in Inferior Corneal Fluorescein Staining to Day 84 | 0.17 units on a scale | Standard Deviation 0.819 |
p-value: 0.000795% CI: [0.1, 0.38]t-test, 2 sided
Primary
Ocular Symptom: Change From Baseline in Visual-Related Subscale of the Symptom Functional Scale Score to Day 84
The symptom functional scale is a validated instrument for ocular surface diseases, measuring the ocular symptoms, vision-related function, and environmental triggers. The 12 items of the symptom functional scale questionnaire were graded on a scale of 0 (none of the time) to 4 (all of the time). The index consisted of 3 sub scales: symptoms (sensitivity to light, gritty sensation, pain, blurred vision, and poor vision \[Items 1-5\]), visual-related sub scale of the symptom functional scale (ability to read, drive at night, use a computer, watch television \[Items 6-9\]), and environmental triggers (windy conditions, low humidity, air conditioning \[Items 10-12\]). The symptom functional scale was scored on a scale of 0 to 100, with higher scores representing greater disability. Negative change from baseline indicates improvement.
Time frame: Baseline (Day 0) to Day 84
Population: ITT population with LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lifitegrast 5.0% | Ocular Symptom: Change From Baseline in Visual-Related Subscale of the Symptom Functional Scale Score to Day 84 | -0.11 units on a scale | Standard Deviation 0.829 |
| Placebo | Ocular Symptom: Change From Baseline in Visual-Related Subscale of the Symptom Functional Scale Score to Day 84 | -0.12 units on a scale | Standard Deviation 0.762 |
p-value: 0.78695% CI: [-0.15, 0.11]t-test, 2 sided