Efficacy and Safety of AL-4943A Ophthalmic Solution in Patients With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to assess the safety and efficacy of AL-4943A ophthalmic solution for the treatment of ocular itching associated with allergic conjunctivitis using the Conjunctival Allergen Challenge (CAC) model.

Detailed Description
-----------------
This study consisted of 5 Visits. Eligible patients underwent allergy testing using the Conjunctival Allergen Challenge (CAC) model, which reproduces the signs and symptoms of Seasonal Allergic Conjunctivitis by replicating the natural disease process. Patients demonstrating a positive reaction to the CAC at Visit 1 (screening) and Visit 2 (confirmatory) were randomized to treatment at Visit 3 (Day 0). The test article was instilled at Visit 3, with treatment efficacy CAC performed at 24 hours duration of action. The test article was instilled again at Visit 4 (Day 14), with treatment efficacy CAC performed at 16 hours duration of action. The test article was instilled a final time at Visit 5 (Day 21), with treatment efficacy performed at onset of action.

Official Title
-----------------
A Multi-Center, Randomized, Double-Masked, Vehicle and Active Controlled, Parallel-Group Efficacy and Safety Study of AL-4943A Ophthalmic Solution, 0.77% in Patients With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model

Conditions
-----------------
Allergic Conjunctivitis

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to be dosed in both eyes, able and willing to make the required study visits and to follow instructions. Diagnostic skin test indicative of allergy for cat hair, cat dander, grasses, ragweed, dust mite, dog dander, cockroach and/or trees within 24 months of Visit 1. History of seasonal or perennial allergic conjunctivitis for at least 1 year prior to Visit 1. Positive bilateral CAC response at Visit 1 and Visit 2. 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 requiring frequent use (> 4 days per week) of artificial tears, gels or lubricants, presence of punctal plugs, use of Restasis®, or topical ocular corticosteroids for dryness of eyes. Presence of active blepharitis, active meibomian gland dysfunction, active rosacea affecting the ocular adnexa, follicular conjunctivitis, iritis, preauricular lymphadenopathy, ocular irritation not due to ocular allergy, or any other clinically significant ophthalmic abnormality that may affect the study outcomes. Presumed or actual ocular infection (bacterial, viral or fungal) or history of ocular herpes in either eye as determined by patient history and/or examination within 30 days of Visit 1. Presence of any chronic ocular degenerative condition or active intra-ocular inflammation in either eye that in the opinion of the Investigator is likely to advance/worsen during the time course of the study. Any contraindications or hypersensitivities to the use of the study medication or their components. Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AL-4943A<br>AL-4943A ophthalmic solution, 1 drop to each eye, 3 nonconsecutive days | Drug: AL-4943A ophthalmic solution<br> <br> |
| Placebo Comparator: Vehicle<br>AL-4943A vehicle, 1 drop to each eye, 3 nonconsecutive days | Drug: AL-4943A vehicle<br>* Inactive ingredients used as placebo<br>|
| Active Comparator: Pataday<br>Olopatadine hydrochloride ophthalmic solution, 0.2%, 1 drop to each eye, 3 nonconsecutive days | Drug: Olopatadine hydrochloride ophthalmic solution, 0.2%<br> <br> * Other names: PATADAY®;|

What is the study measuring?
-----------------
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 instillation. Ocular itching was assessed by the patient on a 0-4 scale (0=none to 4=incapacitating itch). Average of ocular itching score over both eyes was analyzed. | 3, 5, and 7 minute timepoints, post-CAC on Day 21 of receiving treatment | 
| Mean Ocular Itching at 16 Hours Duration of Action | A treatment efficacy CAC was performed 16 hours after drop instillation. Ocular itching was assessed by the patient on a 0-4 scale (0=none to 4=incapacitating itch). Average of ocular itching score over both eyes was analyzed. | 3, 5, and 7 minute timepoints, post-CAC on Day 14 of receiving treatment | 

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 instillation. Conjunctival redness was assessed by the investigator on a 0-4 scale (0=none to 4=extremely severe). Average of conjunctival redness score over both eyes was analyzed. | 7, 15, and 20 minute timepoints, post-CAC on Day 21 of receiving treatment | 
| Mean Conjunctival Redness at 16 Hours Duration of Action | A treatment efficacy CAC was performed 16 hours after drop instillation. Conjunctival redness was assessed by the investigator on a 0-4 scale (0=none to 4=extremely severe). Average of conjunctival redness score over both eyes was analyzed. | 7, 15, and 20 minute timepoints, post-CAC on Day 14 of receiving treatment | 
| Mean Total Redness at 24 Hours Duration of Action | A treatment efficacy CAC was performed 24 hours after drop instillation. Total redness (0-12) is defined as the sum of ciliary redness (0-4 scale, from 0=none to 4=extremely severe), conjunctival redness (0-4 scale, from 0=none to 4=extremely severe), and episcleral redness (0-4 scale, from 0=none to 4=extremely severe). Average of total redness score over both eyes was analyzed. | 7, 15, and 20 minute timepoints, post-CAC on Day 1 of receiving treatment | 
| Mean Ocular Itching at 24 Hours Duration of Action | A treatment efficacy CAC was performed 24 hours after drop instillation. Ocular itching was assessed by the patient on a 0-4 scale (0=none to 4=incapacitating itch). Average of ocular itching score over both eyes was analyzed. | 3, 5, and 7 minute timepoints, post-CAC on Day 1 of receiving treatment | 
| Mean Conjunctival Redness at 24 Hours Duration of Action | A treatment efficacy CAC was performed 24 hours after drop instillation. Conjunctival redness was assessed by the investigator on a 0-4 scale (0=none to 4=extremely severe). Average of conjunctival redness score over both eyes was analyzed. | 7, 15, and 20 minute timepoints, post-CAC on Day 1 of receiving treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Allergic Conjunctivitis, Ocular Allergy