Atopic Conjunctivitis
Conditions
Brief summary
This study evaluates the efficacy and safety of Cyclosporine 0.010% eye drops in the treatment of Atopic Keratoconjunctivitis (chronic and severe inflammation of the eye). The study consists of a double-masked phase, and open-labeled phase, and an open-labeled maintenance phase. For the first 3 months of the study, patients will receive either masked Cyclosporine 0.010% eye drops or vehicle four times daily; for the next 6 months, patients may receive open-labeled Cyclosporine 0.010% eye drops four times daily. At month 9, patients who are in remission, will be re-randomized to receive either open-labeled Cyclosporine 0.010% eye drops four times daily or twice daily.
Interventions
DRUGCyclosporine Vehicle
Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months.
DRUGCyclosporine 0.010%
Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a clinical diagnosis of Atopic Keratoconjunctivitis (chronic and severe inflammation of the eye) * Be on stable doses of your current AKC medications for at least 2 weeks
Exclusion criteria
* You have used contact lenses within 48 hours of Day 1 or think you may have to wear contact lenses during the study * You are pregnant, breastfeeding, or planning to become pregnant during the study * You have used a calcineurin inhibitors (e.g. topical tacrolimus or topical pimecrolimus) on or around your eyes including eyelids within 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Treatment Responders | Baseline, Month 2 | Treatment responders are defined as patients with a ≥ 1 grade improvement from baseline in punctate corneal staining score and a ≥ 4 grade improvement from baseline in composite symptom score in the study eye. The punctate corneal staining score is assessed on a scale of 0 to 5 (0 is ≤2 dots and 5 is \>316 dots (approximately) or ulcer/erosion). The composite symptom score is based on 5 symptoms (itching, tearing, ocular discomfort, photophobia, mucous discharge). The composite symptom score (0 to 15) is the sum of 5 symptoms (each symptom is assessed on a scale of 0=absent to 3=severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Punctate Corneal Staining Responders | Month 2 | Punctate corneal staining responders defined as patients achieving a punctate corneal staining score of 0 or 1 in the study eye. Punctate corneal staining is assessed on a scale of 0 to 5 where 0 is ≤2 dots, 1 is \>2 dots but ≤ 10 dots, 2 is \> 10 dots but ≤ 32 dots, 3 is \> 32 dots but ≤ 100 dots (approximately), 4 is \> 100 dots (approximately) but ≤ 316 dots (approximately), and 5 is \>316 dots (approximately) or ulcer/erosion. |
| Percentage of Patients With an Improvement in the Composite Symptom Score | Baseline, Month 2 | Composite symptom score improvement is defined as a 4 or more grade decrease from baseline in composite symptom score in the study eye. The composite symptom score is based on 5 symptoms (itching, tearing, ocular discomfort, photophobia, mucous discharge). Each of the 5 symptoms is assessed on a scale of 0=absent to 3=severe. The composite symptom score is the sum of all 5 individual symptom scores, where 0 is no symptoms and 15 is the most severe symptoms. |
| Percentage of Patients With an Improvement in the Punctate Corneal Staining Score | Baseline, Month 2 | Punctate corneal staining improvement is defined as a 1 or more grade decrease from baseline in the study eye. The punctate corneal staining score is assessed on a scale of 0 to 5 where 0 is ≤2 dots, 1 is \>2 dots but ≤ 10 dots, 2 is \> 10 dots but ≤ 32 dots, 3 is \> 32 dots but ≤ 100 dots (approximately), 4 is \> 100 dots (approximately) but ≤ 316 dots (approximately), and 5 is \>316 dots (approximately) or ulcer/erosion. |
Countries
Australia, Canada, Czechia, France, Germany, India, Israel, Italy, New Zealand, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Per protocol defined pre-specified criteria, both eyes could qualify for treatment. However, only one eye was designated as the study eye.
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporine Ophthalmic Solution (COS) Followed by COS Cyclosporine ophthalmic solution 0.010% administered 4 times a day to the qualified eye(s) for up to 12 months; at Month 9 the dose may be adjusted to 2 times a day. | 89 |
| Placebo Followed by COS Placebo (cyclosporine vehicle) administered 4 times a day to the qualified eye(s) for 3 months followed by cyclosporine ophthalmic solution 0.010% up to 9 additional months; at Month 9 the dose may be adjusted to 2 times a day. | 87 |
| Total | 176 |
Baseline characteristics
| Characteristic | Cyclosporine Ophthalmic Solution (COS) Followed by COS | Placebo Followed by COS | Total |
|---|---|---|---|
| Age, Customized 18 to <30 years | 15 Participants | 13 Participants | 28 Participants |
| Age, Customized <18 years | 7 Participants | 8 Participants | 15 Participants |
| Age, Customized 30 to <50 years | 32 Participants | 38 Participants | 70 Participants |
| Age, Customized 50 to <65 years | 27 Participants | 22 Participants | 49 Participants |
| Age, Customized >=65 years | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Female | 46 Participants | 39 Participants | 85 Participants |
| Sex: Female, Male Male | 43 Participants | 48 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 171 | 16 / 87 |
| serious Total, serious adverse events | 11 / 171 | 3 / 87 |
Outcome results
Primary
Percentage of Treatment Responders
Treatment responders are defined as patients with a ≥ 1 grade improvement from baseline in punctate corneal staining score and a ≥ 4 grade improvement from baseline in composite symptom score in the study eye. The punctate corneal staining score is assessed on a scale of 0 to 5 (0 is ≤2 dots and 5 is \>316 dots (approximately) or ulcer/erosion). The composite symptom score is based on 5 symptoms (itching, tearing, ocular discomfort, photophobia, mucous discharge). The composite symptom score (0 to 15) is the sum of 5 symptoms (each symptom is assessed on a scale of 0=absent to 3=severe).
Time frame: Baseline, Month 2
Population: Intent to Treat: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporine Ophthalmic Solution (COS) Followed by COS | Percentage of Treatment Responders | 21.3 Percentage of Patients |
| Placebo | Percentage of Treatment Responders | 17.2 Percentage of Patients |
Secondary
Percentage of Patients With an Improvement in the Composite Symptom Score
Composite symptom score improvement is defined as a 4 or more grade decrease from baseline in composite symptom score in the study eye. The composite symptom score is based on 5 symptoms (itching, tearing, ocular discomfort, photophobia, mucous discharge). Each of the 5 symptoms is assessed on a scale of 0=absent to 3=severe. The composite symptom score is the sum of all 5 individual symptom scores, where 0 is no symptoms and 15 is the most severe symptoms.
Time frame: Baseline, Month 2
Population: Intent to Treat: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporine Ophthalmic Solution (COS) Followed by COS | Percentage of Patients With an Improvement in the Composite Symptom Score | 30.3 Percentage of Patients |
| Placebo | Percentage of Patients With an Improvement in the Composite Symptom Score | 28.7 Percentage of Patients |
Secondary
Percentage of Patients With an Improvement in the Punctate Corneal Staining Score
Punctate corneal staining improvement is defined as a 1 or more grade decrease from baseline in the study eye. The punctate corneal staining score is assessed on a scale of 0 to 5 where 0 is ≤2 dots, 1 is \>2 dots but ≤ 10 dots, 2 is \> 10 dots but ≤ 32 dots, 3 is \> 32 dots but ≤ 100 dots (approximately), 4 is \> 100 dots (approximately) but ≤ 316 dots (approximately), and 5 is \>316 dots (approximately) or ulcer/erosion.
Time frame: Baseline, Month 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporine Ophthalmic Solution (COS) Followed by COS | Percentage of Patients With an Improvement in the Punctate Corneal Staining Score | 42.7 Percentage of Patients |
| Placebo | Percentage of Patients With an Improvement in the Punctate Corneal Staining Score | 42.5 Percentage of Patients |
Secondary
Percentage of Punctate Corneal Staining Responders
Punctate corneal staining responders defined as patients achieving a punctate corneal staining score of 0 or 1 in the study eye. Punctate corneal staining is assessed on a scale of 0 to 5 where 0 is ≤2 dots, 1 is \>2 dots but ≤ 10 dots, 2 is \> 10 dots but ≤ 32 dots, 3 is \> 32 dots but ≤ 100 dots (approximately), 4 is \> 100 dots (approximately) but ≤ 316 dots (approximately), and 5 is \>316 dots (approximately) or ulcer/erosion.
Time frame: Month 2
Population: Intent to Treat: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporine Ophthalmic Solution (COS) Followed by COS | Percentage of Punctate Corneal Staining Responders | 24.7 Percentage of Patients |
| Placebo | Percentage of Punctate Corneal Staining Responders | 23.0 Percentage of Patients |