Primary objective: To evaluate the efficacy of once daily doses of QAW039, as measured by EASI after 12 weeks of treatment, relative to placebo, in adult patients with moderate to severe AD. To evaluate safety and tolerability.Secondary objectives:…
ID
Source
Brief title
Condition
- Allergic conditions
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
EASI score week 12, adverse effects.
Secondary outcome
EASI score week 4 and 8.
Background summary
Atopic dermatitis (AD) is an itching, chronically relapsing skin condition. It
is maily localized in the face, behind the ears, on the hairy part of the head,
on the trunk and arms and legs. The onset is mostly at the age of 3 months.
After the age of 10 years mainly the hands, feet, elbows and knees are
affected. In some adults the disease is mainly localized in the face and neck.
It is often associated with elevated serum IgE levels and a personal or family
history of allergies, allergic rhinitis, and asthma. The prevalence of AD has
been reported to be at least 10-15% of children in Europe.
Topical corticosteroids are the mainstay of therapy but their value in patients
with extensive disease is limited by the need for topical application and
short-term use. Long-term use of topical corticosteroids is not recommended due
to the potential to cause local and systemic side effects (e.g. skin atrophy,
impairment of hypothalamic-pituitary-adrenal axis function, and growth
retardation). Treatment options for patients who are not controlled with
topical treatments include phototherapy, methotrexate, and cyclosporine.
QAW039 is a highly selective and potent oral antagonist of prostaglandin D2
(PGD2) that binds to the CRTh2 receptor. CRTh2 inhibitors have been shown to
exert clinical efficacy in asthma and allergic rhinitis. Circulating T-cells
and eosinophils of atopic dermatitis patients express CRTh2 receptors
correlating to disease severity. Please see the Investigator*s Brochure for
more information on the mechanism of action and characteristics of QAW039.
This non-confirmatory clinical study will assess the efficacy and safety of
QAW039 in adult patients with AD over 12 weeks of treatment.
Study objective
Primary objective: To evaluate the efficacy of once daily doses of QAW039, as
measured by EASI after 12 weeks of treatment, relative to placebo, in adult
patients with moderate to severe AD. To evaluate safety and tolerability.
Secondary objectives: To evaluate the efficacy of QAW039, as measured by EASI,
after 4 and 8 weeks of treatment.
Study design
Randomized, double-blind placebo-controlled parallel group, phase II study.
Randomization (3:1) to:
* QAW039 450 mg orally, once daily.
* Placebo.
Screening 4 weeks, treatment 12 weeks, follow-up 8 weeks.
Rescue medication.
Approx. 92 patients.
Intervention
Treatment with QAW039 or placebo.
Study burden and risks
Risk: Adverse effects of study medication. Changes in current asthma
medication. Stepping down budesonide.
Burden: 10 visits in approx. 24 weeks.
Blood tests 10 times (5-65 ml/occasion, 345 ml in total).
Pregnancy test 4 times.
Skin test 4 times.
Skin biopsy 2 times.
ECG 6 times.
Questionnaires (4) 7 times.
Daily diary (medication use and symptoms).
When no positive result of atopy patch test was found at baseline (Visit 3),
atopy patch test will not be performed at Visit 7/8 and Visit 7 may be dropped.
Optional substudies:
* Pharmacogenetic blood test (10 ml).
* Biomarker tests: (3 times extra skin biopsy.
* Photographs of lesions in the face.
Raapopseweg 1
Arnhem 6834 DP
NL
Raapopseweg 1
Arnhem 6834 DP
NL
Listed location countries
Age
Inclusion criteria
* Male or female adults aged 18-65 years.
* Atopic dermatitis (AD) (see protocol page 34 for details).
* Stable AD, EASI score *15 at screening.
* Has 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.
Exclusion criteria
* History of serious allergic reactions to any allergen (see protocol page 35 for details).
* Clinically significant ECG abnormalities (see protocol page 35 for details).
* History of long QT syndrome or QTc measured at Visit 2 (Fridericia method) is prolonged (>450 ms for males and females).
* Use of topical prescription treatment within 2 weeks prior to initial dosing of study drug. Exception: see protocol page 35 for details.
* Recent previous systemic treatment. See protocol page 35 for types of treatment en wash-out.
* Patients on maintenance immunotherapy who either began their allergen specific immunotherapy regimen or had a clinically relevant change to their immunotherapy within 1 month prior to granting informed consent.
* High dose statin therapy (see protocol page 36 for details).
* Excessive exposure to UV light in the 3 weeks prior to screening (see protocol page 36 for details).
* BMI < 17 or > 40 kg/m2.
* Pregnancy and breast feeding. Inadequate contraception, if relevant.
* Serious co-morbidities (see protocol page 37 for details).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2012-005321-78-NL |
| CCMO | NL45361.060.13 |