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

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

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.

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.