Efficacy and Tolerance of Nova22007 Versus Vehicle in Patients With Vernal Keratoconjunctivitis (VKC)

Sponsor
Santen SAS (Industry)
Overall Status
Completed
CT.gov ID
NCT00328653
Collaborator
(none)
118
Enrollment
1
Location
3
Arms

Study Details

Study Description

Brief Summary

The primary objective of this study is:
  • To assess the efficacy of Nova22007, a cyclosporine A (CsA), 0.05% and 0.1% versus vehicle in patients with vernal keratoconjunctivitis (VKC) after a 4-week treatment period.
The secondary objectives of this study are:
  • To compare the safety and ocular tolerance of Nova22007 0.05% and 0.1%;

  • To assess the long term safety and ocular tolerance of Nova22007 0.05% and 0.1%; and

  • To assess the decrease in frequency of concomitant artificial tears use.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Cyclosporine NOVA22007 0.05%
  • Drug: Cyclosporine NOVA22007 0.1%
  • Drug: Vehicle
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
118 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Official Title:
Phase II/III, Multicenter, Double-Masked, Randomized, Parallel Group, Dose Ranging, Controlled Trial of Efficacy and Tolerance of Nova22007 (Cyclosporine A [CSA] 0.05% & 0.1% Ophthalmic Cationic Emulsion) Versus Vehicle in Patients With VKC
Study Start Date :
May 1, 2006
Actual Primary Completion Date :
Feb 22, 2007

Arms and Interventions

ArmIntervention/Treatment
Experimental: NOVA22007 0.05%

four times daily

Drug: Cyclosporine NOVA22007 0.05%

Experimental: NOVA22007 0.1%

four times daily

Drug: Cyclosporine NOVA22007 0.1%

Sham Comparator: Vehicle

administered four times daily

Drug: Vehicle

Outcome Measures

Primary Outcome Measures

  1. Overall Rating of Subjective Symptoms of VKC in Period I [Week 4]

    The primary criteria of the trial was the overall rating of subjective symptoms in ocular symptoms of VKC as compared to Baseline and assessed at Week 4 (Month 1) based on a five-point scale based on BenEzra trial (BenEzra 1986): = Overall worsening of the subjective findings. = No change in the symptoms. = Slight improvement with the child still unable to participate in all normal daily activities. = Marked improvement despite temporary mild itching or mucus discharge. = Completely free of all symptoms.

  2. Overall Rating of Objective Symptoms of VKC in Period I [Week 4]

    Overall rating of objective signs was to be assessed under the slit lamp by the Investigator and recorded on a five-point scale based on BenEzra trial (BenEzra 1986): Intense congestion of conjunctival vessels, perilimbal injection, or corneal involvement with the papillary proliferations more extensive or similar to the situation recorded before treatment in at least one of the eyes. The overall condition was assessed as better than before treatment in both eyes. Total re-epithelialisation of the cornea although slight conjunctival and perilimbal hyperaemia and papillary proliferations remains in both eyes. Only slight conjunctival hyperaemia without perilimbal injection or papillary proliferations in at least one eye Both eyes were quiet with no papillary proliferations or conjunctival or perilimbal injection.

Secondary Outcome Measures

  1. Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I [Up to Month1]

  2. Ocular Tolerance in Period I [Up to Month1]

    Are the tested eye drops (other than concomitant tear substitute ) comfortable?

Eligibility Criteria

Criteria

Ages Eligible for Study:
4 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • At least the two following signs, in at least one eye* (the same eye should fulfill both criteria):

  • Presence of giant papillae with a diameter ≥ 1 mm on the upper tarsal conjunctiva AND

  • Superficial keratitis

  • At least two of the following ocular symptoms with a score > 2 in at least one eye*: burning/stinging, tearing, itching, pain, sticky eyelids, foreign body sensation, mucus discharge, and photophobia.

  • Hyperemia score equal to or greater than 2.

Exclusion Criteria:
  • Concomitant corneal ulcer of infectious origin.

  • Active ocular herpes

  • Disease that could possibly interfere with the interpretation of the study results: active uveitis (defined by Tyndall score > 0), previous history of ocular hypertension or glaucoma, or condition incompatible with the frequent assessments needed by the study.

  • Active herpes.

  • History of malignancy or a recurrence in the last 5 years.

  • Abnormality of nasolacrimal drainage apparatus.

  • Concomitant disease not stabilized within 1 month before Screening Visit (e.g. diabetes with glycemia out of range, trouble with thyroid secretions, etc.) or judged by the investigator to be incompatible with the study (e.g. current systemic infections), or condition incompatible with the frequent assessments needed by the study.

  • Known hypersensitivity to one of the components of the investigational medicinal products (IMP) or test products.

  • Severe systemic allergy requiring systemic treatment at study entry.

  • Female of childbearing potential.

  • History of drug or alcohol addiction (> 50g/day, 5 glasses alcohol/day).

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Groupe Hospitalier Bichat-Claude BernardParisFrance75018

Sponsors and Collaborators

  • Santen SAS

Investigators

  • Principal Investigator: David BenEzra, Pf, Haddassah University Hospital
  • Study Director: Christophe Baudouin, Pf., Hôpital des XV-XX 28 rue de Charenton 75012 Paris

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
, ,
ClinicalTrials.gov Identifier:
NCT00328653
Other Study ID Numbers:
  • NOVATIVE - NVG05L101
First Posted:
May 22, 2006
Last Update Posted:
Dec 14, 2021
Last Verified:
Nov 1, 2021

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleVehicleNOVA22007 0.05%NOVA22007 0.1%
Arm/Group DescriptionVehicle administered four times dailyCyclosporine NOVA22007 0.05% four times dailyCyclosporine NOVA22007 0.1% four times daily
Period Title: Period I
STARTED403939
COMPLETED363936
NOT COMPLETED403
Period Title: Period I
STARTED05853
COMPLETED05049
NOT COMPLETED084

Baseline Characteristics

Arm/Group TitleNOVA22007 0.05%NOVA22007 0.1%VehicleTotal
Arm/Group DescriptionCyclosporine NOVA22007 0.05% four times dailyCyclosporine NOVA22007 0.1% four times dailyVehicle administered four times dailyTotal of all reporting groups
Overall Participants393940118
Age, Customized (years) [Mean (Standard Deviation) ]
Age
8.5
(2.9)
9.4
(3.7)
8.5
(2.4)
8.8
(3.9)
Sex: Female, Male (Count of Participants)
Female
5
12.8%
6
15.4%
11
27.5%
22
18.6%
Male
34
87.2%
33
84.6%
29
72.5%
96
81.4%

Outcome Measures

1. Primary Outcome
TitleOverall Rating of Subjective Symptoms of VKC in Period I
DescriptionThe primary criteria of the trial was the overall rating of subjective symptoms in ocular symptoms of VKC as compared to Baseline and assessed at Week 4 (Month 1) based on a five-point scale based on BenEzra trial (BenEzra 1986): = Overall worsening of the subjective findings. = No change in the symptoms. = Slight improvement with the child still unable to participate in all normal daily activities. = Marked improvement despite temporary mild itching or mucus discharge. = Completely free of all symptoms.
Time FrameWeek 4

Outcome Measure Data

Analysis Population Description
FAS population
Arm/Group TitleVehicleNOVA22007 0.05%NOVA22007 0.1%
Arm/Group DescriptionVehicle administered four times dailyCyclosporine NOVA22007 0.05% four times dailyCyclosporine NOVA22007 0.1% four times daily
Measure Participants403939
1- Overall worsening of the
7
17.9%
1
2.6%
4
10%
2- No change in the symptoms
5
12.8%
3
7.7%
2
5%
3- Slight improvement
10
25.6%
15
38.5%
11
27.5%
4- Marked improvement
15
38.5%
19
48.7%
20
50%
5- Completely free of all symptoms
3
7.7%
1
2.6%
2
5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle, NOVA22007 0.05%
Comments
Type of Statistical Test Superiority
Comments Comparisons of NOVA22007 0.05% to vehicle
Statistical Test of Hypothesisp-Value0.2699
Comments
MethodCochran-Mantel-Haenszel
Comments
Method of EstimationEstimation ParameterM-H Chi-square
Estimated Value1.2187
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Vehicle, NOVA22007 0.1%
Comments
Type of Statistical Test Superiority
Comments Comparisons of NOVA22007 0.1% to vehicle
Statistical Test of Hypothesisp-Value0.2719
Comments
MethodCochran-Mantel-Haenszel
Comments
Method of EstimationEstimation ParameterM-H Chi-square
Estimated Value1.2359
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
TitleChange in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I
Description
Time FrameUp to Month1

Outcome Measure Data

Analysis Population Description
The number of participants is reduced due to missing data.
Arm/Group TitleVehicleNOVA22007 0.05%NOVA22007 0.1%
Arm/Group DescriptionVehicle administered four times dailyCyclosporine NOVA22007 0.05% four times dailyCyclosporine NOVA22007 0.1% four times daily
Measure Participants403939
Week1- Baseline
-0.5
(1.5)
0.1
(2.2)
-0.1
(1.3)
Week2- Baseline
-0.2
(0.9)
-0.4
(1.4)
-0.2
(1.5)
Month1-Baseline
-0.4
(1.9)
-0.5
(1.5)
0.0
(1.9)
3. Secondary Outcome
TitleOcular Tolerance in Period I
DescriptionAre the tested eye drops (other than concomitant tear substitute ) comfortable?
Time FrameUp to Month1

Outcome Measure Data

Analysis Population Description
The number of participants is reduced due to missing data.
Arm/Group TitleVehicleNOVA22007 0.05%NOVA22007 0.1%
Arm/Group DescriptionVehicle administered four times dailyCyclosporine NOVA22007 0.05% four times dailyCyclosporine NOVA22007 0.1% four times daily
Measure Participants403939
No
3
7.7%
11
28.2%
4
10%
Yes
35
89.7%
24
61.5%
34
85%
No
3
7.7%
5
12.8%
6
15%
Yes
34
87.2%
33
84.6%
31
77.5%
No
2
5.1%
8
20.5%
7
17.5%
Yes
34
87.2%
31
79.5%
29
72.5%
4. Primary Outcome
TitleOverall Rating of Objective Symptoms of VKC in Period I
DescriptionOverall rating of objective signs was to be assessed under the slit lamp by the Investigator and recorded on a five-point scale based on BenEzra trial (BenEzra 1986): Intense congestion of conjunctival vessels, perilimbal injection, or corneal involvement with the papillary proliferations more extensive or similar to the situation recorded before treatment in at least one of the eyes. The overall condition was assessed as better than before treatment in both eyes. Total re-epithelialisation of the cornea although slight conjunctival and perilimbal hyperaemia and papillary proliferations remains in both eyes. Only slight conjunctival hyperaemia without perilimbal injection or papillary proliferations in at least one eye Both eyes were quiet with no papillary proliferations or conjunctival or perilimbal injection.
Time FrameWeek 4

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleVehicleNOVA22007 0.05%NOVA22007 0.1%
Arm/Group DescriptionVehicle administered four times dailyCyclosporine NOVA22007 0.05% four times dailyCyclosporine NOVA22007 0.1% four times daily
Measure Participants403939
1.Intense congestion of conjunctival vessels, perilimbal injection, or corneal involvement.
18
46.2%
8
20.5%
7
17.5%
2.The overall condition was assessed as better than before treatment in both eyes.
13
33.3%
17
43.6%
16
40%
3.Total re-epithelialisation of the cornea
4
10.3%
7
17.9%
12
30%
4.Only slight conjunctival hyperaemia in at least one eye
4
10.3%
6
15.4%
2
5%
4.Both eyes were quiet with no papillary proliferations or conjunctival or perilimbal injection.
1
2.6%
1
2.6%
2
5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle, NOVA22007 0.05%
Comments
Type of Statistical Test Superiority
Comments Comparisons of NOVA22007 0.05% to vehicle
Statistical Test of Hypothesisp-Value0.0386
Comments
MethodCochran-Mantel-Haenszel
Comments
Method of EstimationEstimation ParameterM-H-Chi-square
Estimated Value4.2925
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Vehicle, NOVA22007 0.1%
Comments
Type of Statistical Test Superiority
Comments Comparisons of NOVA22007 0.1% to vehicle
Statistical Test of Hypothesisp-Value0.0208
Comments
MethodCochran-Mantel-Haenszel
Comments
Method of EstimationEstimation ParameterM-H-Chi-square
Estimated Value5.3007
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time FrameFrom the time the patient gave informed consent until the last trial visit at month 4.
Adverse Event Reporting Description
Arm/Group TitlePlaceboPeriod I- NOVA22007 0.05%Period I-NOVA22007 0.1%Period II- NOVA22007 0.05%Period II-NOVA22007 0.1%
Arm/Group DescriptionLow Dose RegimenHigh Dose Regimen
All Cause Mortality
PlaceboPeriod I- NOVA22007 0.05%Period I-NOVA22007 0.1%Period II- NOVA22007 0.05%Period II-NOVA22007 0.1%
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/40 (0%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Serious Adverse Events
PlaceboPeriod I- NOVA22007 0.05%Period I-NOVA22007 0.1%Period II- NOVA22007 0.05%Period II-NOVA22007 0.1%
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/40 (0%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Respiratory, thoracic and mediastinal disorders
ASTHMA0/40 (0%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Other (Not Including Serious) Adverse Events
PlaceboPeriod I- NOVA22007 0.05%Period I-NOVA22007 0.1%Period II- NOVA22007 0.05%Period II-NOVA22007 0.1%
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total14/40 (35%) 14/39 (35.9%) 12/39 (30.8%) 17/58 (29.3%) 11/53 (20.8%)
Ear and labyrinth disorders
Ear Pain0/40 (0%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 1/53 (1.9%)
Eye disorders
Allergic keratitis9/40 (22.5%) 3/39 (7.7%) 8/39 (20.5%) 1/58 (1.7%) 0/53 (0%)
Visual acuity reduced1/40 (2.5%) 0/39 (0%) 3/39 (7.7%) 3/58 (5.2%) 1/53 (1.9%)
Ocular hyperaemia1/40 (2.5%) 2/39 (5.1%) 2/39 (5.1%) 0/58 (0%) 0/53 (0%)
Blepharitis0/40 (0%) 0/39 (0%) 1/39 (2.6%) 0/58 (0%) 0/53 (0%)
Corneal Epithelium disorder1/40 (2.5%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Corneal neovascularisation0/40 (0%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Keratitis0/40 (0%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Ocular discomfort0/40 (0%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Conjunctivitis0/40 (0%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Corneal Ulcer3/40 (7.5%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Gastrointestinal disorders
Abdominal Pain0/40 (0%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 1/53 (1.9%)
General disorders
Instillation site pain2/40 (5%) 0/39 (0%) 1/39 (2.6%) 0/58 (0%) 1/53 (1.9%)
Instillation site pruritus1/40 (2.5%) 5/39 (12.8%) 4/39 (10.3%) 3/58 (5.2%) 1/53 (1.9%)
Drug intolerance0/40 (0%) 2/39 (5.1%) 0/39 (0%) 4/58 (6.9%) 1/53 (1.9%)
Hyperthermia0/40 (0%) 1/39 (2.6%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Instillation site lacrimation0/40 (0%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 1/53 (1.9%)
Pain0/40 (0%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Instillation Site Irritation0/40 (0%) 4/39 (10.3%) 2/39 (5.1%) 2/58 (3.4%) 4/53 (7.5%)
Infections and infestations
Bronchitis0/40 (0%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 1/53 (1.9%)
Gastroenteritis0/40 (0%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 1/53 (1.9%)
Otitis externa0/40 (0%) 1/39 (2.6%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Varicella0/40 (0%) 0/39 (0%) 1/39 (2.6%) 0/58 (0%) 0/53 (0%)
Injury, poisoning and procedural complications
Accident0/40 (0%) 0/39 (0%) 1/39 (2.6%) 0/58 (0%) 0/53 (0%)
Face injury1/40 (2.5%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Skin Laceration0/40 (0%) 1/39 (2.6%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Nervous system disorders
Headache0/40 (0%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 1/53 (1.9%)
Respiratory, thoracic and mediastinal disorders
Asthma0/40 (0%) 0/39 (0%) 0/39 (0%) 1/58 (1.7%) 0/53 (0%)
Cough1/40 (2.5%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Epistaxis0/40 (0%) 1/39 (2.6%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Pharyngolaryngeal pain0/40 (0%) 1/39 (2.6%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Skin and subcutaneous tissue disorders
Eczema0/40 (0%) 0/39 (0%) 1/39 (2.6%) 0/58 (0%) 0/53 (0%)
Urticaria1/40 (2.5%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 0/53 (0%)
Skin Irritation1/40 (2.5%) 0/39 (0%) 0/39 (0%) 0/58 (0%) 0/53 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleR&D Quality Manager
OrganizationSanten Inc
Phone415 268 9199
Emailevelyn.chikere@santen.com
Responsible Party:
, ,
ClinicalTrials.gov Identifier:
NCT00328653
Other Study ID Numbers:
  • NOVATIVE - NVG05L101
First Posted:
May 22, 2006
Last Update Posted:
Dec 14, 2021
Last Verified:
Nov 1, 2021