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

Vernal Keratoconjunctivitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01751126
• Other study ID #: NVG09B113
• Status: Completed
• Phase: Phase 3
• Start date: April 29, 2013
• Est. completion date: February 2016

Study information

• Verified date: March 2022
• Source: Santen SAS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 169
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Conjunctivitis, Allergic
• Keratoconjunctivitis
• Vernal Keratoconjunctivitis

Intervention

Drug:
• NOVA22007 ''Ciclosporin''
Sterile, ophthalmic cationic oil-in-water emulsion containing 1 mg/ml Ciclosporin.
• Placebo
Sterile, drug-free, cationic ophthalmic oil-in-water emulsion containing 0 mg/ml Ciclosporin.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Santen SAS

Countries where clinical trial is conducted

United States,  Croatia,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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