Efficacy and Safety of an Ophthalmic Solution in Patients With Allergic Conjunctivitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate an ophthalmic solution for the treatment of ocular itching associated with allergic conjunctivitis using the Conjunctival Allergen Challenge (CAC) model.

Detailed Description
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Enrolled participants will be tested for the presence of common allergies using the Conjunctival Allergen Challenge (CAC) model. Drops of increasing concentration of a solubilized allergen will be instilled in both eyes until a positive reaction occurred. The test will be repeated to confirm the allergic reaction. Participants with confirmed reactions will be administered the test article (Day 0) and undergo a CAC 24 hours post-instillation (Day 1). On Day 14, participants will be administered the test article and undergo an additional CAC.

Official Title
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Phase 3, Efficacy and Safety Study of AL-4943A Ophthalmic Solution, 0.77% in Patients With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model

Conditions
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Allergic Conjunctivitis

Intervention / Treatment
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* Drug: AL-4943A ophthalmic solution
* Drug: Olopatadine hydrochloride ophthalmic solution, 0.2%
* Drug: Olopatadine hydrochloride ophthalmic solution, 0.1%
* Drug: AL-4943A ophthalmic solution vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to be dosed in both eyes, able and willing to make the required study visits and to follow instructions. Negative urine pregnancy test if female of childbearing potential and use adequate birth control throughout the study period. Diagnostic skin test indicative of allergy for cat hair, cat dander, grasses, ragweed, dust mite, dog dander, cockroach and/or trees within 24 months prior to Visit 1 or at Visit 1. History of seasonal or perennial allergic conjunctivitis for at least 1 year prior to Visit 1. Best-corrected visual acuity of 55 or greater in each eye as measured by ETDRS (letters read method). Manifest a positive bilateral Conjunctival Allergen Challenge (CAC) test response. Willing to discontinue contact lens wear for at least 72 hours prior to Visit 1 and throughout the study. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Known history or presence of persistent dry eye syndrome, or currently requires frequent use of artificial tears, gels or lubricants, presence of punctal plugs, use of Restasis®, or topical ocular corticosteroids for dryness of eyes. Presence of an ocular condition that may affect the study outcomes. History or evidence of ocular surgery (including refractive procedures such as LASIK, PRK and RK) within 6 months of Visit 1. Presence of signs/symptoms of active allergic conjunctivitis at the start of Visits 1, 2, 3A, or 4. History of anaphylactic reaction to any allergens used in this study. Current evidence or recent (within 6 months) history of severe, unstable, or uncontrolled medical conditions and/or other relevant systemic diseases. Use of any disallowed medication without protocol-specified washout period prior to Visit 1, or during the study. Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AL-4943A<br>AL-4943A ophthalmic solution, 1 drop per eye Day 0, followed by 1 drop per eye Day 14 | Drug: AL-4943A ophthalmic solution<br> <br> |
| Active Comparator: PATADAY<br>Olopatadine hydrochloride ophthalmic solution, 0.2%, 1 drop per eye Day 0, followed by 1 drop per eye Day 14 | Drug: Olopatadine hydrochloride ophthalmic solution, 0.2%<br> <br> * Other names: PATADAY®;|
| Active Comparator: PATANOL<br>Olopatadine hydrochloride ophthalmic solution, 0.1%, 1 drop per eye Day 0, followed by 1 drop per eye Day 14 | Drug: Olopatadine hydrochloride ophthalmic solution, 0.1%<br> <br> * Other names: PATANOL®;|
| Placebo Comparator: Vehicle<br>AL-4943A ophthalmic solution vehicle, 1 drop per eye Day 0, followed by 1 drop per eye Day 14 | Drug: AL-4943A ophthalmic solution vehicle<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Ocular Itching at Onset of Action | A treatment efficacy CAC was performed 27 minutes after drop installation. Ocular itching was assessed by the participant on a 0-4 scale (0= none, 4 = incapacitating itch). Average of ocular itching score over both eyes was analyzed. | Day 14 (3, 5, and 7 minutes post-CAC) | 
| Mean Ocular Itching at 24 Hours Duration of Action | A treatment efficacy CAC was performed 24 hours after drop instillation on Day 0. Ocular itching was assessed by the participant on a 0-4 scale (0= none, 4 = incapacitating itch). Average of ocular itching score over both eyes was analyzed. | Day 1 (3, 5, and 7 minutes post-CAC) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Conjunctival Redness at Onset of Action | A treatment efficacy CAC was performed 27 minutes after drop installation. Conjunctival redness was assessed by the investigator on a 0-4 scale (0=none, 4=extremely severe). Average of conjunctival redness score over both eyes was analyzed. | Day 14 (7, 15, and 20 minutes post-CAC) | 
| Mean Conjunctival Redness at 24 Hours Duration of Action | A treatment efficacy CAC was performed 24 hours after drop instillation on Day 0. Conjunctival redness was assessed by the investigator on a 0-4 scale (0=none, 4=extremely severe). Average of conjunctival redness score over both eyes was analyzed. | Day 1 (7, 15, and 20 minutes post-CAC) | 
| Mean Total Redness at Onset of Action | A treatment efficacy CAC was performed 27 minutes after drop installation. Conjunctival redness, ciliary redness, and episcleral redness were assessed by the investigator on 0-4 scale (0=none, 4=extremely severe). Total redness is a composite variable summing conjunctival redness, ciliary redness, and episcleral redness scores (resultant score 0-12). The average of total redness over both eyes was analyzed. | Day 14 (7, 15, and 20 minutes post-CAC) | 
| Mean Total Redness at 24 Hours Duration of Action | A treatment efficacy CAC was performed 24 hours after drop instillation on Day 0. Conjunctival redness, ciliary redness, and episcleral redness were assessed by the investigator on 0-4 scale (0=none, 4=extremely severe). Total redness is a composite variable summing conjunctival redness, ciliary redness, and episcleral redness scores (resultant score 0-12). The average of total redness over both eyes was analyzed. | Day 1 (7, 15, and 20 minutes post-CAC) | 
| Proportion of Ocular Itching Responders at Onset of Action | A treatment efficacy CAC was performed 27 minutes after drop installation. Ocular itching was assessed by the participant on a 0-4 scale (0= none, 4 = incapacitating itch). A responder was defined as a participant with zero-itch (a score of zero on ocular itching for both eyes) or with at least 2 units reduction in ocular itching relative to the baseline confirmatory CAC score. Ocular itching score was averaged across both eyes and over the 3 post-CAC assessments (3, 5, and 7 minutes) for the calculation of units reduction. Proportion of Ocular Itching Responders is reported as a percentage. | Day 14 | 
| Proportion of Itch Responders at 24 Hours Duration of Action | A treatment efficacy CAC was performed 24 hours after drop instillation on Day 0. Ocular itching was assessed by the participant on a 0-4 scale (0= none, 4 = incapacitating itch). A responder was defined as a participant with zero-itch (a score of zero on ocular itching for both eyes) or with at least 2 units reduction in ocular itching relative to the baseline confirmatory CAC score. Ocular itching score was averaged across both eyes and over the 3 post-CAC assessments (3, 5, and 7 minutes) for the calculation of units reduction. Proportion of Ocular Itching Responders is reported as a percentage. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allergic conjunctivitis, Olopatadine HCl solution, Conjunctival Allergen Challenge, Itching eyes, Ocular allergies, PATADAY, PATANOL