Atopic Dermatitis
Conditions
Brief summary
The purpose of this study is to determine whether OC000459 is in reducing disease severity and preventing flares in people with moderate to severe atopic dermatitis (AD).
Detailed description
The study will include patients with a Th2 high eosinophilic phenotype who typically have more severe disease and are prone to flare.
Interventions
DRUGOC000459
Oral CRTH2 antagonist
Sponsors
Atopix Therapeutics, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 48 Years
Healthy volunteers
No
Inclusion criteria
1. Atopic dermatitis as defined by a score of at least 9 on the Nottingham Eczema Severity Score, stratified into moderate (score 9 to 11 inclusive) and severe (score 12 to 15 inclusive) disease. 2. Fully documented history of the use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI). Subjects without a fully documented history will be excluded from the study. 3. Male and female subjects with moderate to severe atopic dermatitis treated with by TCS and/or TCI (with or without emollients) at the time of screening and over the previous month. 4. Subjects must have had at least 1 AD flare in the previous 6 months.
Exclusion criteria
1. Receipt of any forbidden medication including over the counter preparations and herbal medicines within 14 days of the first dosing day with the exception of paracetamol up to a maximum of 2g daily. 2. Use of systemic steroids within 4 weeks of the screening visit, light therapy or immunosuppressants within 2 months of the screening visit. 3. Use of NSAIDs. 4. Subjects initially diagnosed with AD aged 2 years or over will be excluded unless they have either coexisting or a history of asthma and/or allergic rhinoconjunctivitis. 5. Subjects with contact dermatitis will be excluded. 6. Subjects with acute skin infection or acute disease flares. Subjects with active flares during the screening to randomisation period (visits 1 to 2) may be managed according to normal clinical practice and be rescreened once their flares are no longer active. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eczema Area and Severity Index (EASI) Compared to Placebo at Week 16 | EASI was measured at baseline (week 0) and 16 weeks after dosing. | The EASI scoring system uses a defined process to grade the severity of the signs of eczema and the extent affected in four regions of the body: head and neck, trunk, upper extremities and lower extremities. The scale ranges from 0 to 72 and the severity strata for the EASI are as follows: 0 clear; 0.1-1.0 almost clear; 1.1-7.0 mild; 7.1-21.0 =moderate; 21.1-50.0 severe; 50.1-72.0 very severe. When assessing response to therapy a reduction of 7 or more is considered to be clinically meaningful. |
Secondary
| Measure | Time frame |
|---|---|
| Rate of Flares | over 16 weeks |
Countries
United Kingdom
Participant flow
Recruitment details
142 patients were randomised. One patient withdrew prior to dosing meaning that there was 141 patients in the safety set. 2 further patients withdrew prior to the first efficacy measurement which means there were 139 patients in the full analysis set.
Participants by arm
| Arm | Count |
|---|---|
| OC000459 Tablets 50 mg orally once a day
OC000459: CRTH2 inhibitor | 69 |
| Placebo Tablets Orally once a day
OC000459: CRTH2 inhibitor | 70 |
| Total | 139 |
Baseline characteristics
| Characteristic | OC000459 Tablets | Placebo Tablets | Total |
|---|---|---|---|
| Age, Continuous | 31.6 years STANDARD_DEVIATION 8.42 | 30.9 years STANDARD_DEVIATION 8.54 | 31.2 years STANDARD_DEVIATION 8.46 |
| Sex: Female, Male Female | 29 Participants | 31 Participants | 60 Participants |
| Sex: Female, Male Male | 40 Participants | 39 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 52 / 70 | 47 / 71 |
| serious Total, serious adverse events | 2 / 70 | 6 / 71 |
Outcome results
Primary
Change From Baseline in Eczema Area and Severity Index (EASI) Compared to Placebo at Week 16
The EASI scoring system uses a defined process to grade the severity of the signs of eczema and the extent affected in four regions of the body: head and neck, trunk, upper extremities and lower extremities. The scale ranges from 0 to 72 and the severity strata for the EASI are as follows: 0 clear; 0.1-1.0 almost clear; 1.1-7.0 mild; 7.1-21.0 =moderate; 21.1-50.0 severe; 50.1-72.0 very severe. When assessing response to therapy a reduction of 7 or more is considered to be clinically meaningful.
Time frame: EASI was measured at baseline (week 0) and 16 weeks after dosing.
Population: Adjusted mean change from baseline EASI at Week 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OC000459 Tablets | Change From Baseline in Eczema Area and Severity Index (EASI) Compared to Placebo at Week 16 | -3.8 units on a scale | Standard Error 1.72 |
| Placebo Tablets | Change From Baseline in Eczema Area and Severity Index (EASI) Compared to Placebo at Week 16 | -6.1 units on a scale | Standard Error 1.71 |
Secondary
Rate of Flares
Time frame: over 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OC000459 Tablets | Rate of Flares | 2.879 flares | Standard Deviation 2.8679 |
| Placebo Tablets | Rate of Flares | 2.646 flares | Standard Deviation 4.7922 |