Efficacy and Tolerance of Nova22007 Versus Vehicle in Patients With Vernal Keratoconjunctivitis (VKC)
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 Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/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
- 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.
- 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
- Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I [Up to Month1]
- Ocular Tolerance in Period I [Up to Month1]
Are the tested eye drops (other than concomitant tear substitute ) comfortable?
Eligibility Criteria
Criteria
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
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Groupe Hospitalier Bichat-Claude Bernard | Paris | France | 75018 |
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.- NOVATIVE - NVG05L101
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Vehicle | NOVA22007 0.05% | NOVA22007 0.1% |
---|---|---|---|
Arm/Group Description | Vehicle administered four times daily | Cyclosporine NOVA22007 0.05% four times daily | Cyclosporine NOVA22007 0.1% four times daily |
Period Title: Period I | |||
STARTED | 40 | 39 | 39 |
COMPLETED | 36 | 39 | 36 |
NOT COMPLETED | 4 | 0 | 3 |
Period Title: Period I | |||
STARTED | 0 | 58 | 53 |
COMPLETED | 0 | 50 | 49 |
NOT COMPLETED | 0 | 8 | 4 |
Baseline Characteristics
Arm/Group Title | NOVA22007 0.05% | NOVA22007 0.1% | Vehicle | Total |
---|---|---|---|---|
Arm/Group Description | Cyclosporine NOVA22007 0.05% four times daily | Cyclosporine NOVA22007 0.1% four times daily | Vehicle administered four times daily | Total of all reporting groups |
Overall Participants | 39 | 39 | 40 | 118 |
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
Title | Overall Rating of Subjective Symptoms of VKC in Period I |
---|---|
Description | 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. |
Time Frame | Week 4 |
Outcome Measure Data
Analysis Population Description |
---|
FAS population |
Arm/Group Title | Vehicle | NOVA22007 0.05% | NOVA22007 0.1% |
---|---|---|---|
Arm/Group Description | Vehicle administered four times daily | Cyclosporine NOVA22007 0.05% four times daily | Cyclosporine NOVA22007 0.1% four times daily |
Measure Participants | 40 | 39 | 39 |
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 Hypothesis | p-Value | 0.2699 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | M-H Chi-square |
Estimated Value | 1.2187 | |
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 Hypothesis | p-Value | 0.2719 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | M-H Chi-square |
Estimated Value | 1.2359 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I |
---|---|
Description | |
Time Frame | Up to Month1 |
Outcome Measure Data
Analysis Population Description |
---|
The number of participants is reduced due to missing data. |
Arm/Group Title | Vehicle | NOVA22007 0.05% | NOVA22007 0.1% |
---|---|---|---|
Arm/Group Description | Vehicle administered four times daily | Cyclosporine NOVA22007 0.05% four times daily | Cyclosporine NOVA22007 0.1% four times daily |
Measure Participants | 40 | 39 | 39 |
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)
|
Title | Ocular Tolerance in Period I |
---|---|
Description | Are the tested eye drops (other than concomitant tear substitute ) comfortable? |
Time Frame | Up to Month1 |
Outcome Measure Data
Analysis Population Description |
---|
The number of participants is reduced due to missing data. |
Arm/Group Title | Vehicle | NOVA22007 0.05% | NOVA22007 0.1% |
---|---|---|---|
Arm/Group Description | Vehicle administered four times daily | Cyclosporine NOVA22007 0.05% four times daily | Cyclosporine NOVA22007 0.1% four times daily |
Measure Participants | 40 | 39 | 39 |
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%
|
Title | Overall Rating of Objective Symptoms of VKC in Period I |
---|---|
Description | 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. |
Time Frame | Week 4 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Vehicle | NOVA22007 0.05% | NOVA22007 0.1% |
---|---|---|---|
Arm/Group Description | Vehicle administered four times daily | Cyclosporine NOVA22007 0.05% four times daily | Cyclosporine NOVA22007 0.1% four times daily |
Measure Participants | 40 | 39 | 39 |
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 Hypothesis | p-Value | 0.0386 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | M-H-Chi-square |
Estimated Value | 4.2925 | |
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 Hypothesis | p-Value | 0.0208 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | M-H-Chi-square |
Estimated Value | 5.3007 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | From the time the patient gave informed consent until the last trial visit at month 4. | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||||
Arm/Group Title | Placebo | Period I- NOVA22007 0.05% | Period I-NOVA22007 0.1% | Period II- NOVA22007 0.05% | Period II-NOVA22007 0.1% | |||||
Arm/Group Description | Low Dose Regimen | High Dose Regimen | ||||||||
All Cause Mortality |
||||||||||
Placebo | Period I- NOVA22007 0.05% | Period I-NOVA22007 0.1% | Period II- NOVA22007 0.05% | Period II-NOVA22007 0.1% | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Serious Adverse Events |
||||||||||
Placebo | Period I- NOVA22007 0.05% | Period I-NOVA22007 0.1% | Period II- NOVA22007 0.05% | Period II-NOVA22007 0.1% | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Respiratory, thoracic and mediastinal disorders | ||||||||||
ASTHMA | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
Placebo | Period I- NOVA22007 0.05% | Period I-NOVA22007 0.1% | Period II- NOVA22007 0.05% | Period II-NOVA22007 0.1% | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 14/40 (35%) | 14/39 (35.9%) | 12/39 (30.8%) | 17/58 (29.3%) | 11/53 (20.8%) | |||||
Ear and labyrinth disorders | ||||||||||
Ear Pain | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 1/53 (1.9%) | |||||
Eye disorders | ||||||||||
Allergic keratitis | 9/40 (22.5%) | 3/39 (7.7%) | 8/39 (20.5%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Visual acuity reduced | 1/40 (2.5%) | 0/39 (0%) | 3/39 (7.7%) | 3/58 (5.2%) | 1/53 (1.9%) | |||||
Ocular hyperaemia | 1/40 (2.5%) | 2/39 (5.1%) | 2/39 (5.1%) | 0/58 (0%) | 0/53 (0%) | |||||
Blepharitis | 0/40 (0%) | 0/39 (0%) | 1/39 (2.6%) | 0/58 (0%) | 0/53 (0%) | |||||
Corneal Epithelium disorder | 1/40 (2.5%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Corneal neovascularisation | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Keratitis | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Ocular discomfort | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Conjunctivitis | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Corneal Ulcer | 3/40 (7.5%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Gastrointestinal disorders | ||||||||||
Abdominal Pain | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 1/53 (1.9%) | |||||
General disorders | ||||||||||
Instillation site pain | 2/40 (5%) | 0/39 (0%) | 1/39 (2.6%) | 0/58 (0%) | 1/53 (1.9%) | |||||
Instillation site pruritus | 1/40 (2.5%) | 5/39 (12.8%) | 4/39 (10.3%) | 3/58 (5.2%) | 1/53 (1.9%) | |||||
Drug intolerance | 0/40 (0%) | 2/39 (5.1%) | 0/39 (0%) | 4/58 (6.9%) | 1/53 (1.9%) | |||||
Hyperthermia | 0/40 (0%) | 1/39 (2.6%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Instillation site lacrimation | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 1/53 (1.9%) | |||||
Pain | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Instillation Site Irritation | 0/40 (0%) | 4/39 (10.3%) | 2/39 (5.1%) | 2/58 (3.4%) | 4/53 (7.5%) | |||||
Infections and infestations | ||||||||||
Bronchitis | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 1/53 (1.9%) | |||||
Gastroenteritis | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 1/53 (1.9%) | |||||
Otitis externa | 0/40 (0%) | 1/39 (2.6%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Varicella | 0/40 (0%) | 0/39 (0%) | 1/39 (2.6%) | 0/58 (0%) | 0/53 (0%) | |||||
Injury, poisoning and procedural complications | ||||||||||
Accident | 0/40 (0%) | 0/39 (0%) | 1/39 (2.6%) | 0/58 (0%) | 0/53 (0%) | |||||
Face injury | 1/40 (2.5%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Skin Laceration | 0/40 (0%) | 1/39 (2.6%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Nervous system disorders | ||||||||||
Headache | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 1/53 (1.9%) | |||||
Respiratory, thoracic and mediastinal disorders | ||||||||||
Asthma | 0/40 (0%) | 0/39 (0%) | 0/39 (0%) | 1/58 (1.7%) | 0/53 (0%) | |||||
Cough | 1/40 (2.5%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Epistaxis | 0/40 (0%) | 1/39 (2.6%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Pharyngolaryngeal pain | 0/40 (0%) | 1/39 (2.6%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Skin and subcutaneous tissue disorders | ||||||||||
Eczema | 0/40 (0%) | 0/39 (0%) | 1/39 (2.6%) | 0/58 (0%) | 0/53 (0%) | |||||
Urticaria | 1/40 (2.5%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) | |||||
Skin Irritation | 1/40 (2.5%) | 0/39 (0%) | 0/39 (0%) | 0/58 (0%) | 0/53 (0%) |
Limitations/Caveats
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/Title | R&D Quality Manager |
---|---|
Organization | Santen Inc |
Phone | 415 268 9199 |
evelyn.chikere@santen.com |
- NOVATIVE - NVG05L101