Double-Masked Trial of NOVA22007 (1mg/mL Ciclosporin/Cyclosporine) Versus Vehicle in Pediatric Patients With Active Severe Vernal Keratoconjunctivitis

Study Overview
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Brief Summary
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The objective of this study is to compare the efficacy of two different dosing regimen of NOVA22007 (1mg/ml ciclosporin/cyclosporine) eye drops, emulsion versus placebo (vehicle of the formulation) administered four times a day in patients with severe vernal keratoconjunctivitis after 4 months of treatment.

Official Title
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A Multicenter, Randomized, Double-Masked, 3 Parallel Arms, Placebo Controlled Study to Assess the Efficacy and Safety of NOVA22007 1mg/mL (Ciclosporin/Cyclosporine) Eye Drops, Emulsion Administered in Paediatric Patients With Active Severe Vernal Keratoconjunctivitis With Severe Keratitis

Conditions
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Vernal Keratoconjunctivitis

Intervention / Treatment
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* Drug: NOVA22007 ''Ciclosporin''
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females from 4 to less than 18 years of age. History of at least one recurrence of vernal keratoconjunctivitis (VKC) in the past year prior to enrolment. Patients not receiving any treatment for an established and active VKC; or patients already receiving treatment for their VKC provided treatment is stopped according to the wash-out period specified in the exclusion criteria. Active severe VKC consistent with grade 3 or 4 of Bonini scale (Bonini 2007) with severe keratitis (grade 4 or 5 on the modified Oxford scale). Mean score of 4 subjective symptoms (photophobia, tearing, itching and mucous discharge) ≥ 60 mm using a 100 mm Visual Analogue Scale (where 0 means no symptom and 100 means the worst that have been ever experienced). Exclusion Criteria: Any relevant ocular anomaly other than VKC interfering with the ocular surface including trauma, post radiation keratitis, severe blepharitis, rosacea, corneal ulcer etc. Abnormal lid anatomy, abnormalities of the nasolacrimal drainage system or blinking function in either eye. Active herpes keratitis or history of ocular herpes. Active ocular infection (viral, bacterial, fungal, protozoal). Any ocular diseases other than VKC requiring topical ocular treatment during the course of the study. Contact lenses wear during the study. Topical and/or systemic use of corticosteroids within one week prior to enrolment. Topical ciclosporin (e.g. Restasis®), tacrolimus or sirolimus within 90 days prior to enrolment. Scraping of the vernal plaque within one month prior to the Baseline visit. Ocular surgery within 6 months prior to the Baseline visit (excluding surgical treatment of the vernal plaque). Disease not stabilized within 30 days before the Baseline Visit (e.g., diabetes with glycemia out of range, thyroid malfunction, uncontrolled autoimmune disease, current systemic infections) or judged by the investigator to be incompatible with the study. Presence or history of severe systemic allergy. Any systemic immunosuppressant drugs within 90 days before the Baseline Visit. Known hypersensitivity to one of the components of the study or procedural medications (e.g., fluorescein, etc). History of malignancy in the last 5 years. Pregnancy or lactation at the Baseline Visit. History of ocular varicella-zoster or vaccinia virus infection.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum 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: Ciclosporin<br>One drop of ciclosporin (NOVA22007) 1 mg/ml 4 times a day as monotherapy (morning, noon, afternoon and evening). | Drug: NOVA22007 ''Ciclosporin''<br>* Sterile, ophthalmic cationic oil-in-water emulsion containing 1 mg/ml Ciclosporin.<br>|
| Experimental: Ciclosporin/Placebo<br>One drop of ciclosporin (NOVA22007) 1 mg/ml twice a day and one drop of placebo twice a day (active study treatment morning and evening and placebo noon and afternoon) as monotherapy. | Drug: NOVA22007 ''Ciclosporin''<br>* Sterile, ophthalmic cationic oil-in-water emulsion containing 1 mg/ml Ciclosporin.<br>Drug: Placebo<br>* Sterile, drug-free, cationic ophthalmic oil-in-water emulsion containing 0 mg/ml Ciclosporin.<br>|
| Placebo Comparator: Placebo<br>One drop of placebo 4 times a day as monotherapy (morning, noon, afternoon and evening). | Drug: Placebo<br>* Sterile, drug-free, cationic ophthalmic oil-in-water emulsion containing 0 mg/ml Ciclosporin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Penalties Adjusted Composite Efficacy Score (CFS) Score Over the 4 Months | Efficacy was assessed every month during the 4-month treatment phase and compared with Baseline using a composite criterion based on: Keratitis assessed by the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5). On this modified scale, the score 0 corresponded to no staining dots and the score 0.5 to three or less staining dots. A CFS grade of 0 represented complete corneal clearing. Need for rescue medication. Occurrence of corneal ulceration. An efficacy score was calculated as follows: Patient's score at month X = CFS (Baseline) - CFS (Month X) + penalty (ies) Penalty for rescue medication: -1 (per course, with a maximum of 2 courses between 2 scheduled visits) Penalty for corneal ulceration: -1 (per occurrence). A positive value indicated improvement. The maximum CFS is five and the minimum cannot be set due to the number of rescue medication and ulceration which decreases the penalty adjusted CFS. | over the 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Distance Visual Acuity (BCDVA) in 4-month Randomized Period I | Best corrected distance visual acuity (BCDVA) was measured with the patient's best correction and recorded in LogMAR (log of the Minimum Angle of Resolution) A negative LogMar BCDVA measure shows an improvement, whereas positive values indicates poor vision. | Up to Month4 | 
| Best Corrected Distance Visual Acuity (BCDVA) in 8-month Safety FU Period- Period II | Best corrected distance visual acuity (BCDVA) was measured with the patient's best correction and recorded in LogMAR (log of the Minimum Angle of Resolution) A negative LogMar BCDVA measure shows an improvement, whereas positive values indicate poor vision. | Up to Month12 | 
| Number of Courses of Rescue Medication in Period I | Use of rescue medication: the total number of topical corticosteroid courses was assessed at each visit during the 4-month efficacy evaluation treatment period. | Up to Month4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vernal keratoconjunctivitis, ciclosporin, cyclosporine