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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Santen SAS
- 入组人数
- 169
- 试验地点
- 43
- 主要终点
- Average Penalties Adjusted Composite Efficacy Score (CFS) Score Over the 4 Months
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 4 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
Ciclosporin
One drop of ciclosporin (NOVA22007) 1 mg/ml 4 times a day as monotherapy (morning, noon, afternoon and evening).
干预措施: NOVA22007 ''Ciclosporin'' (Drug)
Ciclosporin/Placebo
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.
干预措施: NOVA22007 ''Ciclosporin'' (Drug)
Ciclosporin/Placebo
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.
干预措施: Placebo (Drug)
Placebo
One drop of placebo 4 times a day as monotherapy (morning, noon, afternoon and evening).
干预措施: Placebo (Drug)
结局指标
主要结局
Average Penalties Adjusted Composite Efficacy Score (CFS) Score Over the 4 Months
时间窗: 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.
次要结局
- Best Corrected Distance Visual Acuity (BCDVA) in 4-month Randomized Period I(Up to Month4)
- Best Corrected Distance Visual Acuity (BCDVA) in 8-month Safety FU Period- Period II(Up to Month12)
- Number of Courses of Rescue Medication in Period I(Up to Month4)