Efficacy and Safety Study of Cyclosporine 0.010% to Treat Atopic Keratoconjunctivitis

Study Overview
=================
Brief Summary
-----------------
This study evaluates the efficacy and safety of Cyclosporine 0.010% eye drops in the treatment of Atopic Keratoconjunctivitis (chronic and severe inflammation of the eye). The study consists of a double-masked phase, and open-labeled phase, and an open-labeled maintenance phase. For the first 3 months of the study, patients will receive either masked Cyclosporine 0.010% eye drops or vehicle four times daily; for the next 6 months, patients may receive open-labeled Cyclosporine 0.010% eye drops four times daily. At month 9, patients who are in remission, will be re-randomized to receive either open-labeled Cyclosporine 0.010% eye drops four times daily or twice daily.

Conditions
-----------------
Atopic Conjunctivitis

Intervention / Treatment
-----------------
* Drug: Cyclosporine Vehicle
* Drug: Cyclosporine 0.010%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a clinical diagnosis of Atopic Keratoconjunctivitis (chronic and severe inflammation of the eye) Be on stable doses of your current AKC medications for at least 2 weeks Exclusion Criteria: You have used contact lenses within 48 hours of Day 1 or think you may have to wear contact lenses during the study You are pregnant, breastfeeding, or planning to become pregnant during the study You have used a calcineurin inhibitors (e.g. topical tacrolimus or topical pimecrolimus) on or around your eyes including eyelids within 4 weeks

Ages Eligible for Study
-----------------
Minimum Age: 12 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: Cyclosporine Ophthalmic Solution (COS) followed by COS<br>Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day. | Drug: Cyclosporine 0.010%<br>* Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.<br>|
| Other: Placebo followed by COS<br>Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months followed by cyclosporine ophthalmic solution 0.010% up to 9 additional months; at Month 9 the dose may be adjusted to 2 times a day. | Drug: Cyclosporine Vehicle<br>* Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months.<br>Drug: Cyclosporine 0.010%<br>* Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Treatment Responders | Treatment responders are defined as patients with a ≥ 1 grade improvement from baseline in punctate corneal staining score and a ≥ 4 grade improvement from baseline in composite symptom score in the study eye. The punctate corneal staining score is assessed on a scale of 0 to 5 (0 is ≤2 dots and 5 is >316 dots (approximately) or ulcer/erosion). The composite symptom score is based on 5 symptoms (itching, tearing, ocular discomfort, photophobia, mucous discharge). The composite symptom score (0 to 15) is the sum of 5 symptoms (each symptom is assessed on a scale of 0=absent to 3=severe). | Baseline, Month 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Punctate Corneal Staining Responders | Punctate corneal staining responders defined as patients achieving a punctate corneal staining score of 0 or 1 in the study eye. Punctate corneal staining is assessed on a scale of 0 to 5 where 0 is ≤2 dots, 1 is >2 dots but ≤ 10 dots, 2 is > 10 dots but ≤ 32 dots, 3 is > 32 dots but ≤ 100 dots (approximately), 4 is > 100 dots (approximately) but ≤ 316 dots (approximately), and 5 is >316 dots (approximately) or ulcer/erosion. | Month 2 | 
| Percentage of Patients With an Improvement in the Composite Symptom Score | Composite symptom score improvement is defined as a 4 or more grade decrease from baseline in composite symptom score in the study eye. The composite symptom score is based on 5 symptoms (itching, tearing, ocular discomfort, photophobia, mucous discharge). Each of the 5 symptoms is assessed on a scale of 0=absent to 3=severe. The composite symptom score is the sum of all 5 individual symptom scores, where 0 is no symptoms and 15 is the most severe symptoms. | Baseline, Month 2 | 
| Percentage of Patients With an Improvement in the Punctate Corneal Staining Score | Punctate corneal staining improvement is defined as a 1 or more grade decrease from baseline in the study eye. The punctate corneal staining score is assessed on a scale of 0 to 5 where 0 is ≤2 dots, 1 is >2 dots but ≤ 10 dots, 2 is > 10 dots but ≤ 32 dots, 3 is > 32 dots but ≤ 100 dots (approximately), 4 is > 100 dots (approximately) but ≤ 316 dots (approximately), and 5 is >316 dots (approximately) or ulcer/erosion. | Baseline, Month 2 |