Back to resultsDouble-Masked Trial of NOVA22007 (1mg/mL Ciclosporin/Cyclosporine) Versus Vehicle in Pediatric Patients With Active Severe Vernal Keratoconjunctivitis
Primary Purpose
Vernal Keratoconjunctivitis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
NOVA22007 ''Ciclosporin''
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Vernal Keratoconjunctivitis focused on measuring vernal keratoconjunctivitis, ciclosporin, cyclosporine
Eligibility Criteria
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.
Sites / Locations
- Glendale, CA, USA
- Irvine, CA, USA
- Rancho Cordova, CA, USA
- Miami, FL, USA
- Zagreb, City of Zagreb, HR
- Marseille, Bouches-du-Rhône, FR
- Angers CEDEX 9, Maine-et-Loire, FR
- Amiens CEDEX, Somme, FR
- Tours CEDEX 9, FR
- Paris CEDEX 8, Île-de-France, FR
- Mainz, Rhineland-Palatinate, DE
- Ioannina, Eprius, GR
- Thessaloniki, Macedonia, GR
- Larissa, Thessaly, GR
- Szeged, Csongrád, HU
- Debrecen, Hajdú-Bihar, HU
- Budapest, HU
- Visakhapatnam, Andhra Pradesh, IN
- New Delhi, National Capitol Territory, IN
- Chennai, Tamil Nadu, IN
- Lucknow, Uttar Pradesh, IN
- Be'er-Sheva, IL
- Jerusalem, IL
- Petah-Tikva, IL
- Rehovot, IL
- Tel-Aviv, IL
- Bologna, Emilia-Romagna, IT
- Lavagna, Liguria, IT
- Cinisello, Pisa, IT
- Firenze, Tuscany, IT
- Padova, Veneto, IT
- Messina, Messina, IT
- Vila Nova de Gaia, Douro Litoral, PT
- Lisboa, Extremadura, PT
- Lisboa, Extremadura, PT
- Torrevieja, Alicante, ES
- Barakaldo, Biscay, ES
- San Sebastián, Guipúzcoa, ES
- Aranjuez, Madrid, ES
- A Coruña, A Coruña, ES
- Alicante, Alicante, ES
- Madrid, Madrid, ES
- Madrid, Madrid, ES
- Sevilla, Sevilla, ES
- Valencia, Valencia, ES
- Valencia, Valencia, ES
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Ciclosporin
Ciclosporin/Placebo
Placebo
Arm Description
One drop of ciclosporin (NOVA22007) 1 mg/ml 4 times a day as monotherapy (morning, noon, afternoon and evening).
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.
One drop of placebo 4 times a day as monotherapy (morning, noon, afternoon and evening).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01751126
Brief Title
Double-Masked Trial of NOVA22007 (1mg/mL Ciclosporin/Cyclosporine) Versus Vehicle in Pediatric Patients With Active Severe Vernal Keratoconjunctivitis
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
April 29, 2013 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Santen SAS
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vernal Keratoconjunctivitis
Keywords
vernal keratoconjunctivitis, ciclosporin, cyclosporine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
169 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ciclosporin
Arm Type
Experimental
Arm Description
One drop of ciclosporin (NOVA22007) 1 mg/ml 4 times a day as monotherapy (morning, noon, afternoon and evening).
Arm Title
Ciclosporin/Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One drop of placebo 4 times a day as monotherapy (morning, noon, afternoon and evening).
Intervention Type
Drug
Intervention Name(s)
NOVA22007 ''Ciclosporin''
Intervention Description
Sterile, ophthalmic cationic oil-in-water emulsion containing 1 mg/ml Ciclosporin.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Sterile, drug-free, cationic ophthalmic oil-in-water emulsion containing 0 mg/ml Ciclosporin.
Primary Outcome Measure Information:
Title
Average Penalties Adjusted Composite Efficacy Score (CFS) Score Over the 4 Months
Description
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.
Time Frame
over the 4 months
Secondary Outcome Measure Information:
Title
Best Corrected Distance Visual Acuity (BCDVA) in 4-month Randomized Period I
Description
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.
Time Frame
Up to Month4
Title
Best Corrected Distance Visual Acuity (BCDVA) in 8-month Safety FU Period- Period II
Description
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.
Time Frame
Up to Month12
Title
Number of Courses of Rescue Medication in Period I
Description
Use of rescue medication: the total number of topical corticosteroid courses was assessed at each visit during the 4-month efficacy evaluation treatment period.
Time Frame
Up to Month4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Glendale, CA, USA
City
Glendale
State/Province
California
ZIP/Postal Code
91204
Country
United States
Facility Name
Irvine, CA, USA
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
Rancho Cordova, CA, USA
City
Rancho Cordova
State/Province
California
ZIP/Postal Code
95670
Country
United States
Facility Name
Miami, FL, USA
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Zagreb, City of Zagreb, HR
City
Zagreb
State/Province
City Of Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
Marseille, Bouches-du-Rhône, FR
City
Marseille
State/Province
Bouches-du-Rhône
ZIP/Postal Code
13008
Country
France
Facility Name
Angers CEDEX 9, Maine-et-Loire, FR
City
Angers CEDEX 9
State/Province
Maine-et-Loire
ZIP/Postal Code
49933
Country
France
Facility Name
Amiens CEDEX, Somme, FR
City
Amiens CEDEX
State/Province
Somme
ZIP/Postal Code
80054
Country
France
Facility Name
Tours CEDEX 9, FR
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Paris CEDEX 8, Île-de-France, FR
City
Paris CEDEX 8
State/Province
Île-de-France
ZIP/Postal Code
75877
Country
France
Facility Name
Mainz, Rhineland-Palatinate, DE
City
Mainz
State/Province
Rhineland-Palatinate
ZIP/Postal Code
55131
Country
Germany
Facility Name
Ioannina, Eprius, GR
City
Ioannina
State/Province
Eprius
ZIP/Postal Code
45500
Country
Greece
Facility Name
Thessaloniki, Macedonia, GR
City
Thessaloniki
State/Province
Macedonia
ZIP/Postal Code
54636
Country
Greece
Facility Name
Larissa, Thessaly, GR
City
Larissa
State/Province
Thessaly
ZIP/Postal Code
41110
Country
Greece
Facility Name
Szeged, Csongrád, HU
City
Szeged
State/Province
Csongrád
ZIP/Postal Code
H-6720
Country
Hungary
Facility Name
Debrecen, Hajdú-Bihar, HU
City
Debrecen
State/Province
Hajdú-Bihar
ZIP/Postal Code
H-4031
Country
Hungary
Facility Name
Budapest, HU
City
Budapest
ZIP/Postal Code
H-1085
Country
Hungary
Facility Name
Visakhapatnam, Andhra Pradesh, IN
City
Visakhapatnam
State/Province
Andhra Pradesh
ZIP/Postal Code
530013
Country
India
Facility Name
New Delhi, National Capitol Territory, IN
City
New Delhi
State/Province
National Capitol Territory
ZIP/Postal Code
110002
Country
India
Facility Name
Chennai, Tamil Nadu, IN
City
Chennai
State/Province
Tamil Nadu
ZIP/Postal Code
600006
Country
India
Facility Name
Lucknow, Uttar Pradesh, IN
City
Lucknow
State/Province
Uttar Pradesh
ZIP/Postal Code
226003
Country
India
Facility Name
Be'er-Sheva, IL
City
Be'er-Sheva
ZIP/Postal Code
84101
Country
Israel
Facility Name
Jerusalem, IL
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Petah-Tikva, IL
City
Petah-Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Rehovot, IL
City
Rehovot
ZIP/Postal Code
76100
Country
Israel
Facility Name
Tel-Aviv, IL
City
Tel-Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Bologna, Emilia-Romagna, IT
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Lavagna, Liguria, IT
City
Lavagna
State/Province
Liguria
ZIP/Postal Code
16033
Country
Italy
Facility Name
Cinisello, Pisa, IT
City
Cinisello
State/Province
Pisa
ZIP/Postal Code
56124
Country
Italy
Facility Name
Firenze, Tuscany, IT
City
Firenze
State/Province
Tuscany
ZIP/Postal Code
50139
Country
Italy
Facility Name
Padova, Veneto, IT
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
Messina, Messina, IT
City
Messina
ZIP/Postal Code
98125
Country
Italy
Facility Name
Vila Nova de Gaia, Douro Litoral, PT
City
Vila Nova de Gaia
State/Province
Douro Litoral
ZIP/Postal Code
4434-502
Country
Portugal
Facility Name
Lisboa, Extremadura, PT
City
Lisboa
State/Province
Extremadura
ZIP/Postal Code
1150-199
Country
Portugal
Facility Name
Lisboa, Extremadura, PT
City
Lisboa
State/Province
Extremadura
ZIP/Postal Code
1169-019
Country
Portugal
Facility Name
Torrevieja, Alicante, ES
City
Torrevieja
State/Province
Alicante
ZIP/Postal Code
03186
Country
Spain
Facility Name
Barakaldo, Biscay, ES
City
Barakaldo
State/Province
Biscay
ZIP/Postal Code
48903
Country
Spain
Facility Name
San Sebastián, Guipúzcoa, ES
City
San Sebastián
State/Province
Guipúzcoa
ZIP/Postal Code
20014
Country
Spain
Facility Name
Aranjuez, Madrid, ES
City
Aranjuez
State/Province
Madrid
ZIP/Postal Code
28300
Country
Spain
Facility Name
A Coruña, A Coruña, ES
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Alicante, Alicante, ES
City
Alicante
ZIP/Postal Code
03016
Country
Spain
Facility Name
Madrid, Madrid, ES
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Madrid, Madrid, ES
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Sevilla, Sevilla, ES
City
Sevilla
ZIP/Postal Code
41003
Country
Spain
Facility Name
Valencia, Valencia, ES
City
Valencia
ZIP/Postal Code
46014
Country
Spain
Facility Name
Valencia, Valencia, ES
City
Valencia
ZIP/Postal Code
46015
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Double-Masked Trial of NOVA22007 (1mg/mL Ciclosporin/Cyclosporine) Versus Vehicle in Pediatric Patients With Active Severe Vernal Keratoconjunctivitis
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