Vernal KeratoconjunctivitisPhase 3NCT01751126
Double-Masked Trial of NOVA22007 (1mg/mL Ciclosporin/Cyclosporine) Versus Vehicle in Pediatric Patients With Active Severe Vernal Keratoconjunctivitis
A Phase 3 study testing NOVA22007 ''Ciclosporin'' in people with Vernal Keratoconjunctivitis, run by Santen SAS at 46 sites in 11 countries.
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. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Vernal Keratoconjunctivitis
- What is being tested?
- NOVA22007 ''Ciclosporin''
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 169 participants
- Where
- 46 sitesin 11 countries
- Study dates
- 29 Apr 2013to Feb 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
46 sites in 11 countries.
46 sites in 11 countries
Spain11 sites
A Coruña, A Coruña, ES
A Coruña, 15006
Alicante, Alicante, ES
Alicante, 03016
Aranjuez, Madrid, ES
Aranjuez, Madrid, 28300
Barakaldo, Biscay, ES
Barakaldo, Biscay, 48903
Madrid, Madrid, ES
Madrid, 28009
Madrid, Madrid, ES
Madrid, 28046
San Sebastián, Guipúzcoa, ES
San Sebastián, Guipúzcoa, 20014
Sevilla, Sevilla, ES
Seville, 41003
Torrevieja, Alicante, ES
Torrevieja, Alicante, 03186
Valencia, Valencia, ES
Valencia, 46014
Valencia, Valencia, ES
Valencia, 46015
Italy6 sites
Bologna, Emilia-Romagna, IT
Bologna, Emilia-Romagna, 40138
Cinisello, Pisa, IT
Cinisello Balsamo, Pisa, 56124
Firenze, Tuscany, IT
Florence, Tuscany, 50139
Lavagna, Liguria, IT
Lavagna, Liguria, 16033
Messina, Messina, IT
Messina, 98125
Padova, Veneto, IT
Padova, Veneto, 35128
France5 sites
Amiens CEDEX, Somme, FR
Amiens, Somme, 80054
Angers CEDEX 9, Maine-et-Loire, FR
Angers, Maine-et-Loire, 49933
Marseille, Bouches-du-Rhône, FR
Marseille, Bouches-du-Rhône, 13008
Paris CEDEX 8, Île-de-France, FR
Paris, Île-de-France Region, 75877
Tours CEDEX 9, FR
Tours, 37044
Israel5 sites
Be'er-Sheva, IL
Beersheba, 84101
Jerusalem, IL
Jerusalem, 91120
Petah-Tikva, IL
Petah Tikva, 49100
Rehovot, IL
Rehovot, 76100
Tel-Aviv, IL
Tel Aviv, 64239
United States4 sites
Glendale, CA, USA
Glendale, California, 91204
Irvine, CA, USA
Irvine, California, 92697
Miami, FL, USA
Miami, Florida, 33136
Rancho Cordova, CA, USA
Rancho Cordova, California, 95670
India4 sites
Chennai, Tamil Nadu, IN
Chennai, Tamil Nadu, 600006
Lucknow, Uttar Pradesh, IN
Lucknow, Uttar Pradesh, 226003
New Delhi, National Capitol Territory, IN
New Delhi, National Capitol Territory, 110002
Visakhapatnam, Andhra Pradesh, IN
Visakhapatnam, Andhra Pradesh, 530013
Greece3 sites
Ioannina, Eprius, GR
Ioannina, Eprius, 45500
Larissa, Thessaly, GR
Larissa, Thessaly, 41110
Thessaloniki, Macedonia, GR
Thessaloniki, Macedonia, 54636
Hungary3 sites
Budapest, HU
Budapest, H-1085
Debrecen, Hajdú-Bihar, HU
Debrecen, Hajdú-Bihar, H-4031
Szeged, Csongrád, HU
Szeged, Csongrád megye, H-6720
Portugal3 sites
Lisboa, Extremadura, PT
Lisbon, Extremadura, 1150-199
Lisboa, Extremadura, PT
Lisbon, Extremadura, 1169-019
Vila Nova de Gaia, Douro Litoral, PT
Vila Nova de Gaia, Douro Litoral, 4434-502
Germany1 site
Mainz, Rhineland-Palatinate, DE
Mainz, Rhineland-Palatinate, 55131
About this study
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
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
- Being tested
- NOVA22007 ''Ciclosporin'', Placebo
- Keywords
- vernal keratoconjunctivitis, ciclosporin, cyclosporine
- Medical subject headings
- Conjunctivitis, Allergic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NOVA22007 ''Ciclosporin''Drug
Sterile, ophthalmic cationic oil-in-water emulsion containing 1 mg/ml Ciclosporin.
PlaceboDrug
Sterile, drug-free, cationic ophthalmic oil-in-water emulsion containing 0 mg/ml Ciclosporin.
| Study group | Role | What they receive |
|---|---|---|
| Ciclosporin | Experimental | One drop of ciclosporin (NOVA22007) 1 mg/ml 4 times a day as monotherapy (morning, noon, afternoon and evening). Receives: 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. Receives: Drug: NOVA22007 ''Ciclosporin''; Drug: Placebo |
| Placebo | Placebo comparator | One drop of placebo 4 times a day as monotherapy (morning, noon, afternoon and evening). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: over the 4 months
Secondary outcomes (3)
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.
Measured: Up to Month4
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.
Measured: 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.
Measured: Up to Month4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2012 (estimated)
- Study start29 Apr 2013
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Vernal KeratoconjunctivitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- Santen SAS
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01751126
- Sponsor's protocol ID
- NVG09B113
- Status last verified
- Mar 2022
- First submitted
- 13 Dec 2012
- Last updated
- 28 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01751126
- Acronym / sponsor ID
- NVG09B113
- Conditions
- Vernal Keratoconjunctivitis
- Keywords
- vernal keratoconjunctivitis, ciclosporin, cyclosporine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 169 participants (actual)
- Lead sponsor
- Santen SASIndustry (pharma, biotech, devices)
- Study start
- 29 Apr 2013
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 17 Dec 2012 (estimated)
- Results
- Posted 28 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ciclosporin | Experimental | Drug: NOVA22007 ''Ciclosporin''One drop of ciclosporin (NOVA22007) 1 mg/ml 4 times a day as monotherapy (morning, noon, afternoon and evening). |
| Ciclosporin/Placebo | Experimental | Drug: NOVA22007 ''Ciclosporin'', Drug: PlaceboOne 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. |
| Placebo | Placebo comparator | Drug: PlaceboOne drop of placebo 4 times a day as monotherapy (morning, noon, afternoon and evening). |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NOVA22007 ''Ciclosporin''Sterile, ophthalmic cationic oil-in-water emulsion containing 1 mg/ml Ciclosporin. | Drug | Ciclosporin, Ciclosporin/Placebo |
| PlaceboSterile, drug-free, cationic ophthalmic oil-in-water emulsion containing 0 mg/ml Ciclosporin. | Drug | Ciclosporin/Placebo, Placebo |
Primary outcome
Average Penalties Adjusted Composite Efficacy Score (CFS) Score Over the 4 Months
Time frame: 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.
3 secondary outcomes
Best Corrected Distance Visual Acuity (BCDVA) in 4-month Randomized Period I
Time frame: Up to Month4
Best Corrected Distance Visual Acuity (BCDVA) in 8-month Safety FU Period- Period II
Time frame: Up to Month12
Number of Courses of Rescue Medication in Period I
Time frame: Up to Month4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
46 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NOVA22007 ''Ciclosporin'' in people with Vernal Keratoconjunctivitis, run by Santen SAS at 46 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in Spain, Italy, France, Israel, United States and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Penalties Adjusted Composite Efficacy Score (CFS) Score Over the 4 Months (time frame: over the 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2022.