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

Phase 3

Completed

Conditions: Vernal Keratoconjunctivitis

Interventions: Drug: Placebo
Drug: NOVA22007 ''Ciclosporin''

Registration Number: NCT01751126

Lead Sponsor: Santen SAS

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 169

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	One drop of placebo 4 times a day as monotherapy (morning, noon, afternoon and evening).
Ciclosporin/Placebo	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.
Ciclosporin	NOVA22007 ''Ciclosporin''	One drop of ciclosporin (NOVA22007) 1 mg/ml 4 times a day as monotherapy (morning, noon, afternoon and evening).
Ciclosporin/Placebo	NOVA22007 ''Ciclosporin''	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.

Primary Outcome Measures

Name	Time	Method
Average Penalties Adjusted Composite Efficacy Score (CFS) Score Over the 4 Months	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.

Secondary Outcome Measures

Name	Time	Method
Best Corrected Distance Visual Acuity (BCDVA) in 4-month Randomized Period I	Up to Month4	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.
Best Corrected Distance Visual Acuity (BCDVA) in 8-month Safety FU Period- Period II	Up to Month12	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.
Number of Courses of Rescue Medication in Period I	Up to Month4	Use of rescue medication: the total number of topical corticosteroid courses was assessed at each visit during the 4-month efficacy evaluation treatment period.

Trial Locations

Locations (43): Glendale, CA, USA
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Glendale, California, United States
Rancho Cordova, CA, USA
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Rancho Cordova, California, United States
Thessaloniki, Macedonia, GR
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Thessaloniki, Macedonia, Greece
Mainz, Rhineland-Palatinate, DE
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Mainz, Rhineland-Palatinate, Germany
Szeged, Csongrád, HU
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Szeged, Csongrád, Hungary
Debrecen, Hajdú-Bihar, HU
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Debrecen, Hajdú-Bihar, Hungary
Budapest, HU
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Budapest, Hungary
New Delhi, National Capitol Territory, IN
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New Delhi, National Capitol Territory, India
Visakhapatnam, Andhra Pradesh, IN
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Visakhapatnam, Andhra Pradesh, India
Be'er-Sheva, IL
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Be'er-Sheva, Israel
Padova, Veneto, IT
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Padova, Veneto, Italy
Cinisello, Pisa, IT
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Cinisello, Pisa, Italy
Rehovot, IL
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Rehovot, Israel
Tel-Aviv, IL
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Tel-Aviv, Israel
Messina, Messina, IT
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Messina, Italy
Lisboa, Extremadura, PT
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Lisboa, Extremadura, Portugal
Vila Nova de Gaia, Douro Litoral, PT
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Vila Nova de Gaia, Douro Litoral, Portugal
Barakaldo, Biscay, ES
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Barakaldo, Biscay, Spain
San Sebastián, Guipúzcoa, ES
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San Sebastián, Guipúzcoa, Spain
Torrevieja, Alicante, ES
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Torrevieja, Alicante, Spain
Aranjuez, Madrid, ES
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Aranjuez, Madrid, Spain
A Coruña, A Coruña, ES
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A Coruña, Spain
Alicante, Alicante, ES
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Alicante, Spain
Madrid, Madrid, ES
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Madrid, Spain
Sevilla, Sevilla, ES
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Sevilla, Spain
Valencia, Valencia, ES
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Valencia, Spain
Paris CEDEX 8, Île-de-France, FR
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Paris CEDEX 8, Île-de-France, France
Chennai, Tamil Nadu, IN
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Chennai, Tamil Nadu, India
Marseille, Bouches-du-Rhône, FR
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Marseille, Bouches-du-Rhône, France
Angers CEDEX 9, Maine-et-Loire, FR
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Angers CEDEX 9, Maine-et-Loire, France
Tours CEDEX 9, FR
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Tours, France
Bologna, Emilia-Romagna, IT
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Bologna, Emilia-Romagna, Italy
Amiens CEDEX, Somme, FR
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Amiens CEDEX, Somme, France
Ioannina, Eprius, GR
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Ioannina, Eprius, Greece
Larissa, Thessaly, GR
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Larissa, Thessaly, Greece
Jerusalem, IL
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Jerusalem, Israel
Lavagna, Liguria, IT
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Lavagna, Liguria, Italy
Zagreb, City of Zagreb, HR
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Zagreb, City Of Zagreb, Croatia
Petah-Tikva, IL
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Petah-Tikva, Israel
Lucknow, Uttar Pradesh, IN
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Lucknow, Uttar Pradesh, India
Firenze, Tuscany, IT
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Firenze, Tuscany, Italy
Irvine, CA, USA
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Irvine, California, United States
Miami, FL, USA
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Miami, Florida, United States