Double-Masked Trial of NOVA22007 (1mg/mL Ciclosporin/Cycl... | NCT01751126 | Trialant
NCT01751126
Sponsor
Santen SAS
Status
Completed
Last Update Posted
Mar 28, 2022Actual
Enrollment
169Actual
Phase
Phase 3
Conditions
Vernal Keratoconjunctivitis
Interventions
NOVA22007 ''Ciclosporin''
Placebo
Countries
United States
Croatia
France
Germany
Greece
Hungary
India
Israel
Italy
Portugal
Spain
Protocol Section
Identification Module
NCT ID
NCT01751126
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
NVG09B113
Secondary IDs
Not provided
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
Acronym
Not provided
Organization
Santen SASINDUSTRY
Status Module
Record Verification Date
Mar 2022
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Apr 29, 2013
Primary Completion Date
Feb 2016Actual
Completion Date
Feb 2016Actual
First Submitted Date
Dec 13, 2012
First Submission Date that Met QC Criteria
Dec 13, 2012
First Posted Date
Dec 17, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Jul 8, 2021
Results First Submitted that Met QC Criteria
Mar 2, 2022
Results First Posted Date
Mar 28, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 2, 2022
Last Update Posted Date
Mar 28, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Santen SASINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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 provided
Conditions Module
Conditions
Vernal Keratoconjunctivitis
Keywords
vernal keratoconjunctivitis
ciclosporin
cyclosporine
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
169Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
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).
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
Measure
Description
Time Frame
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
Other Outcomes
Not provided
Eligibility Module
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.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
4 Years
Maximum Age
18 Years
Standard Ages
ChildAdult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Not provided
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Glendale, CA, USA
Glendale
California
91204
United States
Irvine, CA, USA
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
High Dose Regimen
1 drop of CsA (NOVA22007) 1 mg/mL 4 times a day as monotherapy (morning, noon, afternoon and evening).
FG001
Low Dose Regimen
1 drop of CsA (NOVA22007) 1 mg/mL twice a day and 1 drop of placebo twice a day (active study treatment morning and evening and placebo noon and afternoon) as monotherapy.
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
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
Irvine
California
92697
United States
Rancho Cordova, CA, USA
Rancho Cordova
California
95670
United States
Miami, FL, USA
Miami
Florida
33136
United States
Zagreb, City of Zagreb, HR
Zagreb
City of Zagreb
10000
Croatia
Marseille, Bouches-du-Rhône, FR
Marseille
Bouches-du-Rhône
13008
France
Angers CEDEX 9, Maine-et-Loire, FR
Angers
Maine-et-Loire
49933
France
Amiens CEDEX, Somme, FR
Amiens
Somme
80054
France
Tours CEDEX 9, FR
Tours
37044
France
Paris CEDEX 8, Île-de-France, FR
Paris
Île-de-France Region
75877
France
Mainz, Rhineland-Palatinate, DE
Mainz
Rhineland-Palatinate
55131
Germany
Ioannina, Eprius, GR
Ioannina
Eprius
45500
Greece
Thessaloniki, Macedonia, GR
Thessaloniki
Macedonia
54636
Greece
Larissa, Thessaly, GR
Larissa
Thessaly
41110
Greece
Szeged, Csongrád, HU
Szeged
Csongrád megye
H-6720
Hungary
Debrecen, Hajdú-Bihar, HU
Debrecen
Hajdú-Bihar
H-4031
Hungary
Budapest, HU
Budapest
H-1085
Hungary
Visakhapatnam, Andhra Pradesh, IN
Visakhapatnam
Andhra Pradesh
530013
India
New Delhi, National Capitol Territory, IN
New Delhi
National Capitol Territory
110002
India
Chennai, Tamil Nadu, IN
Chennai
Tamil Nadu
600006
India
Lucknow, Uttar Pradesh, IN
Lucknow
Uttar Pradesh
226003
India
Be'er-Sheva, IL
Beersheba
84101
Israel
Jerusalem, IL
Jerusalem
91120
Israel
Petah-Tikva, IL
Petah Tikva
49100
Israel
Rehovot, IL
Rehovot
76100
Israel
Tel-Aviv, IL
Tel Aviv
64239
Israel
Bologna, Emilia-Romagna, IT
Bologna
Emilia-Romagna
40138
Italy
Lavagna, Liguria, IT
Lavagna
Liguria
16033
Italy
Cinisello, Pisa, IT
Cinisello Balsamo
Pisa
56124
Italy
Firenze, Tuscany, IT
Florence
Tuscany
50139
Italy
Padova, Veneto, IT
Padova
Veneto
35128
Italy
Messina, Messina, IT
Messina
98125
Italy
Vila Nova de Gaia, Douro Litoral, PT
Vila Nova de Gaia
Douro Litoral
4434-502
Portugal
Lisboa, Extremadura, PT
Lisbon
Extremadura
1150-199
Portugal
Lisboa, Extremadura, PT
Lisbon
Extremadura
1169-019
Portugal
Torrevieja, Alicante, ES
Torrevieja
Alicante
03186
Spain
Barakaldo, Biscay, ES
Barakaldo
Biscay
48903
Spain
San Sebastián, Guipúzcoa, ES
San Sebastián
Guipúzcoa
20014
Spain
Aranjuez, Madrid, ES
Aranjuez
Madrid
28300
Spain
A Coruña, A Coruña, ES
A Coruña
15006
Spain
Alicante, Alicante, ES
Alicante
03016
Spain
Madrid, Madrid, ES
Madrid
28009
Spain
Madrid, Madrid, ES
Madrid
28046
Spain
Sevilla, Sevilla, ES
Seville
41003
Spain
Valencia, Valencia, ES
Valencia
46014
Spain
Valencia, Valencia, ES
Valencia
46015
Spain
FG002
Placebo
1 drop of placebo 4 times a day as monotherapy.
FG00057 subjects
FG00154 subjects
FG00258 subjects
COMPLETED
FG00051 subjects
FG00143 subjects
FG00249 subjects
NOT COMPLETED
FG0006 subjects
FG00111 subjects
FG0029 subjects
Period II
Type
Comment
Milestone Data
STARTED
FG00072 subjects
FG00170 subjects
FG0020 subjectsFollowing completion of the first period of the trial, all patients were to be administered NOVA22007 (High or Low dose) for a safety 8-month follow-up period.
COMPLETED
FG00072 subjects
FG00170 subjects
FG0020 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
One participant from the High dose regimen withdrew at the first week of randomization and not related to study medication.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
High Dose Regimen
1 drop of CsA (NOVA22007) 1 mg/mL 4 times a day as monotherapy (morning, noon, afternoon and evening).
BG001
Low Dose Regimen
1 drop of CsA (NOVA22007) 1 mg/mL twice a day and 1 drop of placebo twice a day (active study treatment morning and evening and placebo noon and afternoon) as monotherapy.
BG002
Placebo
1 drop of placebo 4 times a day as monotherapy.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00056
BG00154
BG00258
BG003168
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Mean
Standard Deviation
years
Title
Denominators
Categories
Children (4-18 years)
Title
Measurements
BG0009.1± 3.3
BG0019.6± 3.4
BG0028.9± 3.2
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00012
BG00112
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
Posted
Mean
Standard Deviation
Penalties Adjusted CFS Score
over the 4 months
ID
Title
Description
OG000
High Dose Regimen
1 drop of CsA (NOVA22007) 1 mg/mL 4 times a day as monotherapy (morning, noon, afternoon and evening).
OG001
Low Dose Regimen
1 drop of CsA (NOVA22007) 1 mg/mL twice a day and 1 drop of placebo twice a day (active study treatment morning and evening and placebo noon and afternoon) as monotherapy.
OG002
Placebo
1 drop of placebo 4 times a day as monotherapy.
Units
Counts
Participants
OG00056
OG00154
OG00258
Title
Denominators
Categories
Title
Measurements
OG0002.06± 1.44
OG0011.93± 1.37
OG0021.34± 1.22
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
t-test, 2 sided
0.007
ANCOVA with treatment as well as the baseline CFS and the exposure to Vernal keratoconjunctivitis (VKC) seasons (Hochberg procedure).
LS Mean
0.76
2-Sided
95
0.26
1.27
Superiority
OG001
OG002
ANCOVA
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.
SS population
Posted
Mean
Standard Deviation
letters
Up to Month4
ID
Title
Description
OG000
LogMAR - High Dose Regimen
Logarithm of the Minimum Angle of Resolution (LogMAR)
OG001
LogMAR - Low Dose Regimen
OG002
LogMAR-Placebo
OG003
Change From Baseline in LogMAR- High Dose
OG004
Change From Baseline in LogMAR- Low Dose
OG005
Change From Baseline in LogMAR- Placebo
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.
SS population
Posted
Mean
Standard Deviation
letters
Up to Month12
ID
Title
Description
OG000
LogMAR - High Dose Regimen
OG001
LogMAR - Placebo
OG002
LogMAR-Total
OG003
Change From Baseline in LogMAR- High Dose
OG004
Change From Baseline in LogMAR- Placebo
OG005
Change From Baseline in LogMAR- Total
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.
Participants reduced due to missing data
Posted
Count of Participants
Participants
Up to Month4
ID
Title
Description
OG000
High Dose Regimen
1 drop of CsA (NOVA22007) 1 mg/mL 4 times a day as monotherapy (morning, noon, afternoon and evening).
OG001
Low Dose Regimen
1 drop of CsA (NOVA22007) 1 mg/mL twice a day and 1 drop of placebo twice a day (active study treatment morning and evening and placebo noon and afternoon) as monotherapy.
OG002
Placebo
1 drop of placebo 4 times a day as monotherapy.
Units
Counts
Participants
Time Frame
From the time the informed consent form was signed until the last study visit at Month 12.