Atopic Dermatitis
Conditions
Keywords
Atopic eczema, Skin Diseases
Brief summary
The purpose of this study is to determine whether QAW039 is safe and has beneficial effects in people who have moderate to severe atopic dermatitis (AD).
Interventions
DRUGQAW039
Capsules
DRUGPlacebo
Capsules
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Presence of atopic dermatitis confirmed by Itchy skin condition in the past 12 months plus three, or more, of the following: * History of involvement of the skin creases (fronts of elbows, behind knees, fronts of ankles, around neck or around eyes) * Personal history of asthma or hay fever * History of generally dry skin in the past year * Onset before age of 2 years * Visible flexural dermatitis * Patients with an EASI score of ≥15 at screening and stable AD (not currently experiencing an acute flare of their AD). * Patients that have been treated with topical corticosteroids or topical calcineurin inhibitors on at least one occasion, or could not use topical drugs (due to contraindications, side effects, etc.) and are candidates for or have previously received systemic treatment. Key
Exclusion criteria
* History of hypersensitivity to any of the study drugs (including local anesthesia) or to drugs of similar chemical classes (CRTh2 antagonists) * History of serious allergic reactions to any allergen, such as anaphylactic shock or life-threatening asthma, prior intubation, respiratory arrest, hospitalization due to asthma within the last 3 months or seizures as a result of asthma * History of clinically significant ECG abnormalities or screening/baseline ECG that demonstrated clinical significant abnormalities which could affect patient safety or interpretation of study results * History of long QT syndrome or whose QTc interval (Frederica's) was prolonged (\>450 msec for males and females) at screening * Use of topical prescription treatment (e.g., topical corticosteroids, calcineurin inhibitors, antibiotics, etc.) within two weeks prior to initial dosing of study drug. Patient use of emollients was encouraged * Exception: For local atopic dermatitis flares during this 2-week interval, mild topical corticosteroids may be taken short term (up to one week) * Recent previous systemic treatment with phototherapy, systemic antihistamines, immunosuppressive agents (e.g., cyclosporine, mycophenolate, or oral tacrolimus, including therapeutic proteins) * Patients on maintenance immunotherapy who either began their allergen specific immunotherapy regimen or had a clinically relevant change to their immunotherapy within one month prior to granting informed consent * Patients on high-dose statin therapy (\>40 mg fluvastatin or 20 mg simvastatin, atorvastin, pravastatin, or rosuvastatin \[10 mg if Asian\]) * Excessive exposure to UV light in the three weeks prior to study start (screening), including tanning and sun beds and/or planning excessive sunbathing or beach holidays with associated sun bathing during the treatment period * History of hypertrophic scarring * Body mass index \<17 or \>40 kg/m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eczema Area and Severity Index (EASI) | Baseline, 12 weeks | Investigators assessed presence and severity of erythema, induration/papulation, excoriation, and lichenification in four body areas: head/neck (H), upper limbs (UL), trunk (T), and lower limbs (LL). Investigators assigned a severity score from 0 - 3 for each area (none=0, mild=1, moderate=2, and severe=3). Investigators could assign half-points. Investigators also assigned an area score from 0 (no atopic dermatitis lesion in the area) to 6 (entire area is affected) for each area. The weighting factor was 0.1 for head/neck, 0.2 for upper limbs, 0.3 for trunk, and 0.4 for lower limbs. The total body score for each body region was obtained by multiplying the sum of the severity scores of the four key signs by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gave the EASI total, ranging from 0 to 72. A higher score represented greater disease severity. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eczema Area and Severity Index | Baseline, 4 weeks, 8 weeks | Investigators assessed presence and severity of erythema, induration/papulation, excoriation, and lichenification in four body areas: head/neck (H), upper limbs (UL), trunk (T), and lower limbs (LL). Investigators assigned a severity score from 0 - 3 for each area (none=0, mild=1, moderate=2, and severe=3). Investigators could assign half-points. Investigators also assigned an area score from 0 (no atopic dermatitis lesion in the area) to 6 (entire area is affected) for each area. The weighting factor was 0.1 for head/neck, 0.2 for upper limbs, 0.3 for trunk, and 0.4 for lower limbs. The total body score for each body region was obtained by multiplying the sum of the severity scores of the four key signs by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gave the EASI total, ranging from 0 to 72. A higher score represented greater disease severity. A negative change from baseline indicates improvement. |
Countries
Australia, Austria, Belgium, Bulgaria, Germany, Netherlands, Romania, South Africa
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| QAW039 Participants received QAW039 450 mg daily by mouth. | 76 |
| Placebo Participants received matching placebo to QAW039. | 27 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 7 | 3 |
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | QAW039 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 35.5 Years STANDARD_DEVIATION 13.08 | 38.7 Years STANDARD_DEVIATION 9.95 | 36.3 Years STANDARD_DEVIATION 12.37 |
| Sex: Female, Male Female | 27 Participants | 12 Participants | 39 Participants |
| Sex: Female, Male Male | 49 Participants | 15 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 76 | 16 / 27 |
| serious Total, serious adverse events | 1 / 76 | 4 / 27 |
Outcome results
Primary
Change From Baseline in Eczema Area and Severity Index (EASI)
Investigators assessed presence and severity of erythema, induration/papulation, excoriation, and lichenification in four body areas: head/neck (H), upper limbs (UL), trunk (T), and lower limbs (LL). Investigators assigned a severity score from 0 - 3 for each area (none=0, mild=1, moderate=2, and severe=3). Investigators could assign half-points. Investigators also assigned an area score from 0 (no atopic dermatitis lesion in the area) to 6 (entire area is affected) for each area. The weighting factor was 0.1 for head/neck, 0.2 for upper limbs, 0.3 for trunk, and 0.4 for lower limbs. The total body score for each body region was obtained by multiplying the sum of the severity scores of the four key signs by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gave the EASI total, ranging from 0 to 72. A higher score represented greater disease severity. A negative change from baseline indicates improvement.
Time frame: Baseline, 12 weeks
Population: All randomized participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QAW039 | Change From Baseline in Eczema Area and Severity Index (EASI) | -8.65 Score on a scale | Standard Error 0.01 |
| Placebo | Change From Baseline in Eczema Area and Severity Index (EASI) | -6.95 Score on a scale | Standard Error 0.017 |
Secondary
Change From Baseline in Eczema Area and Severity Index
Investigators assessed presence and severity of erythema, induration/papulation, excoriation, and lichenification in four body areas: head/neck (H), upper limbs (UL), trunk (T), and lower limbs (LL). Investigators assigned a severity score from 0 - 3 for each area (none=0, mild=1, moderate=2, and severe=3). Investigators could assign half-points. Investigators also assigned an area score from 0 (no atopic dermatitis lesion in the area) to 6 (entire area is affected) for each area. The weighting factor was 0.1 for head/neck, 0.2 for upper limbs, 0.3 for trunk, and 0.4 for lower limbs. The total body score for each body region was obtained by multiplying the sum of the severity scores of the four key signs by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gave the EASI total, ranging from 0 to 72. A higher score represented greater disease severity. A negative change from baseline indicates improvement.
Time frame: Baseline, 4 weeks, 8 weeks
Population: All randomized participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QAW039 | Change From Baseline in Eczema Area and Severity Index | Week 4 | -6.22 Score on a scale | Standard Error 0.01 |
| QAW039 | Change From Baseline in Eczema Area and Severity Index | Week 8 | -7.49 Score on a scale | Standard Error 0.01 |
| Placebo | Change From Baseline in Eczema Area and Severity Index | Week 4 | -5.89 Score on a scale | Standard Error 0.017 |
| Placebo | Change From Baseline in Eczema Area and Severity Index | Week 8 | -5.61 Score on a scale | Standard Error 0.017 |