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

NCT01751126 | Completed Phase 3 Results DMC

• 1 other identifier: NVG09B113
• Study Type: interventional
• Target: 169
• Locations: 11 countries
• Sites: 46

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.

Conditions

Vernal Keratoconjunctivitis

Keywords

vernal keratoconjunctivitis; ciclosporin; cyclosporine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (3)

Ciclosporin

EXPERIMENTAL

One drop of ciclosporin (NOVA22007) 1 mg/ml 4 times a day as monotherapy (morning, noon, afternoon and evening).

Drug: NOVA22007 ''Ciclosporin''

Ciclosporin/Placebo

EXPERIMENTAL

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''; Drug: Placebo

Placebo

PLACEBO COMPARATOR

One drop of placebo 4 times a day as monotherapy (morning, noon, afternoon and evening).

Drug: Placebo

Interventions

NOVA22007 ''Ciclosporin'' DRUG

Sterile, ophthalmic cationic oil-in-water emulsion containing 1 mg/ml Ciclosporin.

Ciclosporin; Ciclosporin/Placebo

Placebo DRUG

Sterile, drug-free, cationic ophthalmic oil-in-water emulsion containing 0 mg/ml Ciclosporin.

Ciclosporin/Placebo; Placebo

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Santen SAS: lead

Study Sites (46)

Glendale, CA, USA

Glendale, California, 91204, United States

Location

Irvine, CA, USA

Irvine, California, 92697, United States

Location

Rancho Cordova, CA, USA

Rancho Cordova, California, 95670, United States

Location

Miami, FL, USA

Miami, Florida, 33136, United States

Location

Zagreb, City of Zagreb, HR

Zagreb, City of Zagreb, 10000, Croatia

Location

Marseille, Bouches-du-Rhône, FR

Marseille, Bouches-du-Rhône, 13008, France

Location

Angers CEDEX 9, Maine-et-Loire, FR

Angers, Maine-et-Loire, 49933, France

Location

Amiens CEDEX, Somme, FR

Amiens, Somme, 80054, France

Location

Tours CEDEX 9, FR

Tours, 37044, France

Location

Paris CEDEX 8, Île-de-France, FR

Paris, Île-de-France Region, 75877, France

Location

Mainz, Rhineland-Palatinate, DE

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Ioannina, Eprius, GR

Ioannina, Eprius, 45500, Greece

Location

Thessaloniki, Macedonia, GR

Thessaloniki, Macedonia, 54636, Greece

Location

Larissa, Thessaly, GR

Larissa, Thessaly, 41110, Greece

Location

Szeged, Csongrád, HU

Szeged, Csongrád megye, H-6720, Hungary

Location

Debrecen, Hajdú-Bihar, HU

Debrecen, Hajdú-Bihar, H-4031, Hungary

Location

Budapest, HU

Budapest, H-1085, Hungary

Location

Visakhapatnam, Andhra Pradesh, IN

Visakhapatnam, Andhra Pradesh, 530013, India

Location

New Delhi, National Capitol Territory, IN

New Delhi, National Capitol Territory, 110002, India

Location

Chennai, Tamil Nadu, IN

Chennai, Tamil Nadu, 600006, India

Location

Lucknow, Uttar Pradesh, IN

Lucknow, Uttar Pradesh, 226003, India

Location

Be'er-Sheva, IL

Beersheba, 84101, Israel

Location

Jerusalem, IL

Jerusalem, 91120, Israel

Location

Petah-Tikva, IL

Petah Tikva, 49100, Israel

Location

Rehovot, IL

Rehovot, 76100, Israel

Location

Tel-Aviv, IL

Tel Aviv, 64239, Israel

Location

Bologna, Emilia-Romagna, IT

Bologna, Emilia-Romagna, 40138, Italy

Location

Lavagna, Liguria, IT

Lavagna, Liguria, 16033, Italy

Location

Cinisello, Pisa, IT

Cinisello Balsamo, Pisa, 56124, Italy

Location

Firenze, Tuscany, IT

Florence, Tuscany, 50139, Italy

Location

Padova, Veneto, IT

Padua, Veneto, 35128, Italy

Location

Messina, Messina, IT

Messina, 98125, Italy

Location

Vila Nova de Gaia, Douro Litoral, PT

Vila Nova de Gaia, Douro Litoral, 4434-502, Portugal

Location

Lisboa, Extremadura, PT

Lisbon, Extremadura, 1150-199, Portugal

Location

Lisboa, Extremadura, PT

Lisbon, Extremadura, 1169-019, Portugal

Location

Torrevieja, Alicante, ES

Torrevieja, Alicante, 03186, Spain

Location

Barakaldo, Biscay, ES

Barakaldo, Biscay, 48903, Spain

Location

San Sebastián, Guipúzcoa, ES

San Sebastián, Guipúzcoa, 20014, Spain

Location

Aranjuez, Madrid, ES

Aranjuez, Madrid, 28300, Spain

Location

A Coruña, A Coruña, ES

A Coruña, 15006, Spain

Location

Alicante, Alicante, ES

Alicante, 03016, Spain

Location

Madrid, Madrid, ES

Madrid, 28009, Spain

Location

Madrid, Madrid, ES

Madrid, 28046, Spain

Location

Sevilla, Sevilla, ES

Seville, 41003, Spain

Location

Valencia, Valencia, ES

Valencia, 46014, Spain

Location

Valencia, Valencia, ES

Valencia, 46015, Spain

Location

MeSH Terms

Conditions

Conjunctivitis, Allergic

Condition Hierarchy (Ancestors)

Conjunctivitis; Conjunctival Diseases; Eye Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: R&D Quality Manager
• Organization: Santen Inc

evelyn.chikere@santen.com

4152689199

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2012
• First Posted: December 17, 2012
• Study Start: April 29, 2013
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: March 28, 2022
• Results First Posted: March 28, 2022

Record last verified: 2022-03

Locations

IT (6); HU (3); IL (5); PT (3); CR (1); GR (3); FR (5); IN (4); ES (11); DE (1); US (4)