Allergic Conjunctivitis
Conditions
Brief summary
The purpose of this study is to determine whether SAR 1118 at three different concentrations, compared to placebo, is effective in the prevention of the signs and symptoms of allergic conjunctivitis
Interventions
DRUGLifitegrast
Ophthalmic Solution
OTHERPlacebo
Ophthalmic Solution
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 at the time of enrollment * 20/40 vision, or better, in each eye * History of ocular allergies, and a positive skin and ocular allergic reaction to allergens * A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period
Exclusion criteria
* Preauricular lymphadenopathy or any ocular condition that could affect study parameters (particularly, glaucoma, diabetic retinopathy, clinically significant blepharitis, follicular conjunctivitis and iritis) * Have had any ocular infection within the last 30 days * A positive diagnosis of moderate to severe dry eye syndrome (i.e., requiring daily use of artificial tears) * Any significant illness that could be expected to interfere with study parameters * Manifest signs or symptoms of clinically active allergic conjunctivitis in either eye * Use of any investigational product or device within one month prior to Visit 1 or during the study period * Concomitant use of any prohibited medication (antihistamines, corticosteroids, all ocular medications or anti-allergic therapies) during the trial or within the washout period * Any blood donation or significant loss of blood within 56 days of Visit 1 * Any history of autoimmune disease, immunodeficiency disorder, positive HIV, hepatitis B, C, or evidence of acute active hepatitis A (anti-HAV IgM), or organ or bone marrow transplant. Any known history of iritis/uveitis, glaucoma, or other chronic ophthalmologic disorder other than allergic conjunctivitis * 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 3 months prior to Visit 1 * Known history of alcohol abuse and/or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Itching at Day 7 (7 Minutes Post Conjunctival Allergen Challenge [CAC 6]) | Baseline to Day 7 (7 minutes post CAC 6) | Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching. CAC is an initial titration challenge to determine the appropriate allergen and lowest concentration of allergen that produced a positive bilateral allergic response for each subject, defined as ≥ 2 score (0-4 point scale) in ocular itching and conjunctival redness within 10 minutes of the last titration of allergen. |
| Ocular Itching at Day 14 (7 Minutes Post CAC 9) | Baseline to Day 14 (7 minutes post CAC 9) | Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching. |
| Conjunctival Redness at Day 7 (20 Minutes Post CAC 6) | Baseline to Day 7 (20 minutes post CAC 6) | Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness. |
| Conjunctival Redness at Day 14 (20 Minutes Post CAC 9) | Baseline to Day 14 (20 minutes post CAC 9) | Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Baseline to Day 6 (CAC 4), Day 13 (CAC 7) 7 minutes post CAC | Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching. |
| Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Baseline to Day 6 (CAC 4), Day 13 (CAC 7) at 20 minutes post CAC | Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lifitegrast 0.1% | 15 |
| Lifitegrast 1.0% | 15 |
| Lifitegrast 5.0% | 15 |
| Placebo | 15 |
| Total | 60 |
Baseline characteristics
| Characteristic | Lifitegrast 0.1% | Lifitegrast 1.0% | Lifitegrast 5.0% | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 41.67 years STANDARD_DEVIATION 15.207 | 37.67 years STANDARD_DEVIATION 12.613 | 45.33 years STANDARD_DEVIATION 15.891 | 39.13 years STANDARD_DEVIATION 12.212 | 40.95 years STANDARD_DEVIATION 14.019 |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 9 Participants | 6 Participants | 29 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 6 Participants | 9 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 15 | 7 / 15 | 12 / 15 | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 1 / 15 |
Outcome results
Primary
Conjunctival Redness at Day 14 (20 Minutes Post CAC 9)
Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.
Time frame: Baseline to Day 14 (20 minutes post CAC 9)
Population: ITT population with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lifitegrast 0.1% | Conjunctival Redness at Day 14 (20 Minutes Post CAC 9) | 1.92 units on a scale | Standard Deviation 0.686 |
| Lifitegrast 1.0% | Conjunctival Redness at Day 14 (20 Minutes Post CAC 9) | 2.42 units on a scale | Standard Deviation 0.397 |
| Lifitegrast 5.0% | Conjunctival Redness at Day 14 (20 Minutes Post CAC 9) | 2.38 units on a scale | Standard Deviation 0.399 |
| Placebo | Conjunctival Redness at Day 14 (20 Minutes Post CAC 9) | 2.17 units on a scale | Standard Deviation 0.652 |
p-value: 0.1773Wilcoxon rank-sum test
p-value: 0.4222Wilcoxon rank-sum test
p-value: 0.4326Wilcoxon rank-sum test
Primary
Conjunctival Redness at Day 7 (20 Minutes Post CAC 6)
Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.
Time frame: Baseline to Day 7 (20 minutes post CAC 6)
Population: ITT population with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lifitegrast 0.1% | Conjunctival Redness at Day 7 (20 Minutes Post CAC 6) | 2.27 units on a scale | Standard Deviation 0.458 |
| Lifitegrast 1.0% | Conjunctival Redness at Day 7 (20 Minutes Post CAC 6) | 2.48 units on a scale | Standard Deviation 0.406 |
| Lifitegrast 5.0% | Conjunctival Redness at Day 7 (20 Minutes Post CAC 6) | 2.57 units on a scale | Standard Deviation 0.477 |
| Placebo | Conjunctival Redness at Day 7 (20 Minutes Post CAC 6) | 2.52 units on a scale | Standard Deviation 0.427 |
p-value: 0.0578Wilcoxon rank-sum test
p-value: 0.8988Wilcoxon rank-sum test
p-value: 0.4709Wilcoxon rank-sum test
Primary
Ocular Itching at Day 14 (7 Minutes Post CAC 9)
Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching.
Time frame: Baseline to Day 14 (7 minutes post CAC 9)
Population: ITT population with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lifitegrast 0.1% | Ocular Itching at Day 14 (7 Minutes Post CAC 9) | 2.28 units on a scale | Standard Deviation 1.043 |
| Lifitegrast 1.0% | Ocular Itching at Day 14 (7 Minutes Post CAC 9) | 2.50 units on a scale | Standard Deviation 1.191 |
| Lifitegrast 5.0% | Ocular Itching at Day 14 (7 Minutes Post CAC 9) | 2.63 units on a scale | Standard Deviation 0.968 |
| Placebo | Ocular Itching at Day 14 (7 Minutes Post CAC 9) | 2.12 units on a scale | Standard Deviation 0.737 |
p-value: 0.5846Wilcoxon rank-sum test
p-value: 0.1493Wilcoxon rank-sum test
p-value: 0.0404Wilcoxon rank-sum test
Primary
Ocular Itching at Day 7 (7 Minutes Post Conjunctival Allergen Challenge [CAC 6])
Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching. CAC is an initial titration challenge to determine the appropriate allergen and lowest concentration of allergen that produced a positive bilateral allergic response for each subject, defined as ≥ 2 score (0-4 point scale) in ocular itching and conjunctival redness within 10 minutes of the last titration of allergen.
Time frame: Baseline to Day 7 (7 minutes post CAC 6)
Population: Intent-to-treat (ITT) population with last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lifitegrast 0.1% | Ocular Itching at Day 7 (7 Minutes Post Conjunctival Allergen Challenge [CAC 6]) | 2.65 units on a scale | Standard Deviation 0.731 |
| Lifitegrast 1.0% | Ocular Itching at Day 7 (7 Minutes Post Conjunctival Allergen Challenge [CAC 6]) | 2.68 units on a scale | Standard Deviation 1.096 |
| Lifitegrast 5.0% | Ocular Itching at Day 7 (7 Minutes Post Conjunctival Allergen Challenge [CAC 6]) | 3.07 units on a scale | Standard Deviation 0.837 |
| Placebo | Ocular Itching at Day 7 (7 Minutes Post Conjunctival Allergen Challenge [CAC 6]) | 2.88 units on a scale | Standard Deviation 0.41 |
p-value: 0.3235Wilcoxon rank-sum test
p-value: 0.9144Wilcoxon rank-sum test
p-value: 0.3324Wilcoxon rank-sum test
Secondary
Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7)
Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.
Time frame: Baseline to Day 6 (CAC 4), Day 13 (CAC 7) at 20 minutes post CAC
Population: ITT population with LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lifitegrast 0.1% | Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Visit 3: 20 minutes post CAC 4 | 1.82 units on a scale | Standard Deviation 0.594 |
| Lifitegrast 0.1% | Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Visit 5: 20 minutes post CAC 7 | 1.37 units on a scale | Standard Deviation 0.911 |
| Lifitegrast 1.0% | Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Visit 5: 20 minutes post CAC 7 | 2.15 units on a scale | Standard Deviation 0.749 |
| Lifitegrast 1.0% | Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Visit 3: 20 minutes post CAC 4 | 2.15 units on a scale | Standard Deviation 0.725 |
| Lifitegrast 5.0% | Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Visit 3: 20 minutes post CAC 4 | 2.25 units on a scale | Standard Deviation 0.605 |
| Lifitegrast 5.0% | Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Visit 5: 20 minutes post CAC 7 | 1.62 units on a scale | Standard Deviation 1.026 |
| Placebo | Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Visit 3: 20 minutes post CAC 4 | 2.25 units on a scale | Standard Deviation 0.433 |
| Placebo | Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) | Visit 5: 20 minutes post CAC 7 | 1.77 units on a scale | Standard Deviation 0.863 |
Secondary
Ocular Itching at Day 6 (CAC 4), 5 (CAC 7)
Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching.
Time frame: Baseline to Day 6 (CAC 4), Day 13 (CAC 7) 7 minutes post CAC
Population: ITT population with LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lifitegrast 0.1% | Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Visit 3: 7 minutes post CAC 4 | 2.83 units on a scale | Standard Deviation 0.564 |
| Lifitegrast 0.1% | Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Visit 5: 7 minutes post CAC 7 | 2.42 units on a scale | Standard Deviation 1.084 |
| Lifitegrast 1.0% | Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Visit 5: 7 minutes post CAC 7 | 2.62 units on a scale | Standard Deviation 0.778 |
| Lifitegrast 1.0% | Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Visit 3: 7 minutes post CAC 4 | 2.37 units on a scale | Standard Deviation 0.886 |
| Lifitegrast 5.0% | Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Visit 3: 7 minutes post CAC 4 | 3.02 units on a scale | Standard Deviation 0.644 |
| Lifitegrast 5.0% | Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Visit 5: 7 minutes post CAC 7 | 2.63 units on a scale | Standard Deviation 0.972 |
| Placebo | Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Visit 3: 7 minutes post CAC 4 | 2.82 units on a scale | Standard Deviation 0.395 |
| Placebo | Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) | Visit 5: 7 minutes post CAC 7 | 2.38 units on a scale | Standard Deviation 0.388 |