A 52-week, multicenter, randomized, double-blind, placebocontrolled study to assess the efficacy and safety of QAW039 when added to existing asthma therapy in patients with uncontrolled severe asthma

Despite existing therapies, there is still significant unmet medical need in
asthma.
Severe asthma is defined as asthma that requires treatment with high dose
inhaled corticosteroids plus a second controller and/or systemic
corticosteroids. Severe asthma is a heterogeneous condition consisting of
phenotypes such as eosinophilic asthma.This subgroup has also been defined as
"refractory" asthma.
Recurrent exacerbations are a major problem in some patients with severe
asthma. It seems inhalation therapy, and oral cortico-steroids are not as
effective for this sub-group as in the milder forms of asthma.Therefore, there
remains a need for therapy, which is well tolerated, is easy to administrate,
and anti-inflammatory works, in which it suppresses the sputum eosinophils and
thereby reduces the asthma exacerbations.

QAW039 is a CRTh2 antagonist expected to provide benefit in asthma by binding
to CRTh2 receptors on eosinophils, basophils, and T lymphocytes in the blood
and tissues; thus, inhibiting migration and activation of these cells into the
airway tissues and blocking the PGD2-driven release of Th2 cytokines
(Chevalier, et al 2005). Since these are the major effector cells and soluble
factors driving airway inflammation in asthma, treatment with QAW039 should
result in a decrease in these parameters of airway inflammation as well as a
clinical improvement in asthma.

The overall purpose of this study is to determine the efficacy and safety of
QAW039 in patients with inadequately controlled severe
asthma and high eosinophil counts.

In patients with severe asthma and high eosinophil counts (>=250 cells/µl)
receiving SoC asthma therapy, to demonstrate the efficacy (as measured
by rate of moderate-to-severe asthma exacerbations) of at least one dose level
of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of
the 52-week active-treatment epoch.
In patients with severe asthma receiving SoC asthma therapy, to demonstrate the
efficacy (as measured by rate of moderate-to-severe
asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg
once daily), compared with placebo, at the end of the 52-week
active-treatment epoch.

This study uses a randomized, multicenter, double-blind, placebocontrolled
parallel-group study design in which QAW039 or placebo is
added to GINA steps 4 and 5 asthma therapy.
A Screening epoch of approximately 2 weeks (however up to 6 weeks) to assess
eligibility;
A Run-in epoch of a minimum of 2 weeks and a maximum of 6 weeks to collect
baseline data for efficacy variables and compliance with the
Electronic Peak Flow/ eDiary device (if a patient experiences an asthma
exacerbation during the run-in epoch, the run-in epoch must
be extended to 6 weeks to permit for resolution of the asthma exacerbation
before randomization. The run-in epoch should only be
extended beyond 2 weeks (+/- 5 days) for an asthma exacerbation.);
A Treatment epoch of 52 weeks
A Follow-up epoch of 4 weeks, investigational and drug-free, following the last
dose of study drug.

Treatment with 150 mg or 450 mg QAW039 or placebo once daily.

Burden:
Physical examination: 10x
Length: 2x, weight 4x, vital signs 10x
Blood collection: 10x (7-12.25 ml blood per collection)
Urinalysis: 10x
Pregnancy test (females of childbearing potential): 11 x (1x serum, 10x urine)
Spirometry: 19x
Reversibility test: 4x
ECG: 14x
Peak expiratory flow (PEF) (AM and PM) en completion of dairy: Daily during
run-in and treatment period.
FeNO: 4x (= optional)
ECG:14x
Completion of 4 questionnaires: 10 x (at screening 1 instead of 4
questionnaires)

Risks:
Side effects QAW039 and risks of study procedures.