Conjunctivitis, Vernal
Conditions
Keywords
vernal keratoconjunctivitis (VKC), eye, allergy, cyclosporin
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.
Interventions
DRUGCyclosporine NOVA22007 0.05%
DRUGCyclosporine NOVA22007 0.1%
DRUGVehicle
Sponsors
Santen SAS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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): 1. = Overall worsening of the subjective findings. 2. = No change in the symptoms. 3. = Slight improvement with the child still unable to participate in all normal daily activities. 4. = Marked improvement despite temporary mild itching or mucus discharge. 5. = 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): 1. 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. 2. The overall condition was assessed as better than before treatment in both eyes. 3. Total re-epithelialisation of the cornea although slight conjunctival and perilimbal hyperaemia and papillary proliferations remains in both eyes. 4. Only slight conjunctival hyperaemia without perilimbal injection or papillary proliferations in at least one eye 5. Both eyes were quiet with no papillary proliferations or conjunctival or perilimbal injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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? |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NOVA22007 0.05% Cyclosporine NOVA22007 0.05% four times daily | 39 |
| NOVA22007 0.1% Cyclosporine NOVA22007 0.1% four times daily | 39 |
| Vehicle Vehicle administered four times daily | 40 |
| Total | 118 |
Baseline characteristics
| Characteristic | NOVA22007 0.05% | NOVA22007 0.1% | Vehicle | Total |
|---|---|---|---|---|
| Age, Customized Age | 8.5 years STANDARD_DEVIATION 2.9 | 9.4 years STANDARD_DEVIATION 3.7 | 8.5 years STANDARD_DEVIATION 2.4 | 8.8 years STANDARD_DEVIATION 3.9 |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 34 Participants | 33 Participants | 29 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 39 | 0 / 39 | 0 / 58 | 0 / 53 |
| other Total, other adverse events | 14 / 40 | 14 / 39 | 12 / 39 | 17 / 58 | 11 / 53 |
| serious Total, serious adverse events | 0 / 40 | 0 / 39 | 0 / 39 | 1 / 58 | 0 / 53 |
Outcome results
Primary
Overall Rating of Objective Symptoms of VKC in Period I
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): 1. 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. 2. The overall condition was assessed as better than before treatment in both eyes. 3. Total re-epithelialisation of the cornea although slight conjunctival and perilimbal hyperaemia and papillary proliferations remains in both eyes. 4. Only slight conjunctival hyperaemia without perilimbal injection or papillary proliferations in at least one eye 5. Both eyes were quiet with no papillary proliferations or conjunctival or perilimbal injection.
Time frame: Week 4
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle | Overall Rating of Objective Symptoms of VKC in Period I | 4.Only slight conjunctival hyperaemia in at least one eye | 4 Participants |
| Vehicle | Overall Rating of Objective Symptoms of VKC in Period I | 3.Total re-epithelialisation of the cornea | 4 Participants |
| Vehicle | Overall Rating of Objective Symptoms of VKC in Period I | 1.Intense congestion of conjunctival vessels, perilimbal injection, or corneal involvement. | 18 Participants |
| Vehicle | Overall Rating of Objective Symptoms of VKC in Period I | 2.The overall condition was assessed as better than before treatment in both eyes. | 13 Participants |
| Vehicle | Overall Rating of Objective Symptoms of VKC in Period I | 4.Both eyes were quiet with no papillary proliferations or conjunctival or perilimbal injection. | 1 Participants |
| NOVA22007 0.05% | Overall Rating of Objective Symptoms of VKC in Period I | 3.Total re-epithelialisation of the cornea | 7 Participants |
| NOVA22007 0.05% | Overall Rating of Objective Symptoms of VKC in Period I | 1.Intense congestion of conjunctival vessels, perilimbal injection, or corneal involvement. | 8 Participants |
| NOVA22007 0.05% | Overall Rating of Objective Symptoms of VKC in Period I | 2.The overall condition was assessed as better than before treatment in both eyes. | 17 Participants |
| NOVA22007 0.05% | Overall Rating of Objective Symptoms of VKC in Period I | 4.Only slight conjunctival hyperaemia in at least one eye | 6 Participants |
| NOVA22007 0.05% | Overall Rating of Objective Symptoms of VKC in Period I | 4.Both eyes were quiet with no papillary proliferations or conjunctival or perilimbal injection. | 1 Participants |
| NOVA22007 0.1% | Overall Rating of Objective Symptoms of VKC in Period I | 4.Both eyes were quiet with no papillary proliferations or conjunctival or perilimbal injection. | 2 Participants |
| NOVA22007 0.1% | Overall Rating of Objective Symptoms of VKC in Period I | 4.Only slight conjunctival hyperaemia in at least one eye | 2 Participants |
| NOVA22007 0.1% | Overall Rating of Objective Symptoms of VKC in Period I | 1.Intense congestion of conjunctival vessels, perilimbal injection, or corneal involvement. | 7 Participants |
| NOVA22007 0.1% | Overall Rating of Objective Symptoms of VKC in Period I | 3.Total re-epithelialisation of the cornea | 12 Participants |
| NOVA22007 0.1% | Overall Rating of Objective Symptoms of VKC in Period I | 2.The overall condition was assessed as better than before treatment in both eyes. | 16 Participants |
p-value: 0.0386Cochran-Mantel-Haenszel
p-value: 0.0208Cochran-Mantel-Haenszel
Primary
Overall Rating of Subjective Symptoms of VKC in Period I
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): 1. = Overall worsening of the subjective findings. 2. = No change in the symptoms. 3. = Slight improvement with the child still unable to participate in all normal daily activities. 4. = Marked improvement despite temporary mild itching or mucus discharge. 5. = Completely free of all symptoms.
Time frame: Week 4
Population: FAS population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle | Overall Rating of Subjective Symptoms of VKC in Period I | 4- Marked improvement | 15 Participants |
| Vehicle | Overall Rating of Subjective Symptoms of VKC in Period I | 3- Slight improvement | 10 Participants |
| Vehicle | Overall Rating of Subjective Symptoms of VKC in Period I | 1- Overall worsening of the | 7 Participants |
| Vehicle | Overall Rating of Subjective Symptoms of VKC in Period I | 5- Completely free of all symptoms | 3 Participants |
| Vehicle | Overall Rating of Subjective Symptoms of VKC in Period I | 2- No change in the symptoms | 5 Participants |
| NOVA22007 0.05% | Overall Rating of Subjective Symptoms of VKC in Period I | 2- No change in the symptoms | 3 Participants |
| NOVA22007 0.05% | Overall Rating of Subjective Symptoms of VKC in Period I | 1- Overall worsening of the | 1 Participants |
| NOVA22007 0.05% | Overall Rating of Subjective Symptoms of VKC in Period I | 3- Slight improvement | 15 Participants |
| NOVA22007 0.05% | Overall Rating of Subjective Symptoms of VKC in Period I | 4- Marked improvement | 19 Participants |
| NOVA22007 0.05% | Overall Rating of Subjective Symptoms of VKC in Period I | 5- Completely free of all symptoms | 1 Participants |
| NOVA22007 0.1% | Overall Rating of Subjective Symptoms of VKC in Period I | 5- Completely free of all symptoms | 2 Participants |
| NOVA22007 0.1% | Overall Rating of Subjective Symptoms of VKC in Period I | 4- Marked improvement | 20 Participants |
| NOVA22007 0.1% | Overall Rating of Subjective Symptoms of VKC in Period I | 1- Overall worsening of the | 4 Participants |
| NOVA22007 0.1% | Overall Rating of Subjective Symptoms of VKC in Period I | 3- Slight improvement | 11 Participants |
| NOVA22007 0.1% | Overall Rating of Subjective Symptoms of VKC in Period I | 2- No change in the symptoms | 2 Participants |
p-value: 0.2699Cochran-Mantel-Haenszel
p-value: 0.2719Cochran-Mantel-Haenszel
Secondary
Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I
Time frame: Up to Month1
Population: The number of participants is reduced due to missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Week2- Baseline | -0.2 instillations | Standard Deviation 0.9 |
| Vehicle | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Week1- Baseline | -0.5 instillations | Standard Deviation 1.5 |
| Vehicle | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Month1-Baseline | -0.4 instillations | Standard Deviation 1.9 |
| NOVA22007 0.05% | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Week2- Baseline | -0.4 instillations | Standard Deviation 1.4 |
| NOVA22007 0.05% | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Week1- Baseline | 0.1 instillations | Standard Deviation 2.2 |
| NOVA22007 0.05% | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Month1-Baseline | -0.5 instillations | Standard Deviation 1.5 |
| NOVA22007 0.1% | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Week1- Baseline | -0.1 instillations | Standard Deviation 1.3 |
| NOVA22007 0.1% | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Month1-Baseline | 0.0 instillations | Standard Deviation 1.9 |
| NOVA22007 0.1% | Change in Mean Daily Number of Unpreserved Artificial Tears Instillations in Period I | Week2- Baseline | -0.2 instillations | Standard Deviation 1.5 |
Secondary
Ocular Tolerance in Period I
Are the tested eye drops (other than concomitant tear substitute ) comfortable?
Time frame: Up to Month1
Population: The number of participants is reduced due to missing data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Vehicle | Ocular Tolerance in Period I | Week1 | Yes | 35 Participants |
| Vehicle | Ocular Tolerance in Period I | Week2 | Yes | 34 Participants |
| Vehicle | Ocular Tolerance in Period I | Week2 | No | 3 Participants |
| Vehicle | Ocular Tolerance in Period I | Week1 | No | 3 Participants |
| Vehicle | Ocular Tolerance in Period I | Month1 | Yes | 34 Participants |
| Vehicle | Ocular Tolerance in Period I | Month1 | No | 2 Participants |
| NOVA22007 0.05% | Ocular Tolerance in Period I | Week2 | No | 5 Participants |
| NOVA22007 0.05% | Ocular Tolerance in Period I | Week1 | No | 11 Participants |
| NOVA22007 0.05% | Ocular Tolerance in Period I | Week1 | Yes | 24 Participants |
| NOVA22007 0.05% | Ocular Tolerance in Period I | Week2 | Yes | 33 Participants |
| NOVA22007 0.05% | Ocular Tolerance in Period I | Month1 | No | 8 Participants |
| NOVA22007 0.05% | Ocular Tolerance in Period I | Month1 | Yes | 31 Participants |
| NOVA22007 0.1% | Ocular Tolerance in Period I | Week1 | No | 4 Participants |
| NOVA22007 0.1% | Ocular Tolerance in Period I | Month1 | Yes | 29 Participants |
| NOVA22007 0.1% | Ocular Tolerance in Period I | Month1 | No | 7 Participants |
| NOVA22007 0.1% | Ocular Tolerance in Period I | Week1 | Yes | 34 Participants |
| NOVA22007 0.1% | Ocular Tolerance in Period I | Week2 | No | 6 Participants |
| NOVA22007 0.1% | Ocular Tolerance in Period I | Week2 | Yes | 31 Participants |