Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.
Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.
This study aimed to determine the efficacy and safety of QAW039 150 mg and QAW039 450 mg,
 compared with placebo, when added to GINA (Global Initiative for Asthma) steps 4 and 5
 standard-of- care (SoC) asthma therapy (GINA 2016) in the following two populations:

 -  patient with inadequately controlled severe asthma and high eosinophil counts at
 baseline (eosinophil count at Visit 1 ≥250 cells/ µl) (sub-population)

 -  patients with inadequately controlled severe asthma (overall study population)

 Inadequate control is defined as partly controlled or uncontrolled asthma (GINA 2016).
This study used a randomized, multicenter, double-blind, placebo-controlled parallel-group
 design in which QAW039 150 mg or QA039 450 mg or placebo was added to standard of care, GINA
 steps 4 and 5 asthma therapy.

 The study included:

 -  Screening period of up to 2 weeks to assess eligibility;

 -  Run-in period of approximately 2 weeks and a maximum of 6 weeks on placebo to collect
 baseline data for efficacy variables and compliance with the Electronic Peak Flow/
 eDiary device. Upon completion of the run-in period, all patients who met the
 eligibility criteria were randomized to one of three treatments: QAW039 150 mg or QAW039
 450 mg or placebo once daily in a ratio of 1:1:1.

 -  Treatment period of 52 weeks (assessment period for all Primary and Secondary Outcome
 Measures). Clinic visits were scheduled approximately 4 weeks after randomization and
 then at approximately 8-week intervals during the active-treatment period. Phone calls
 occurred at specified time points between visits occurring at 8-week intervals. Patients
 who had successfully completed 52 weeks of treatment in this study were offered an
 optional participation in a safety study (CQAW039A2315).

 -  Follow-up period of 4 weeks, investigational and drug-free, following the last dose of
 study drug. A follow-up visit occurred approximately 4 weeks (i.e., approximately 30
 days) following the last dose of study therapy to complete safety assessments and
 pregnancy testing (if applicable). the follow-up period applied to all patients except
 those patients who had entered the safety study (CQAW039A2315) directly after the Week
 52 study visit.
Inclusion Criteria:

 -  Written informed consent and assent (if applicable).

 -  Male and female patients aged ≥12 years (or ≥lower age limit allowed by health
 authority and/or ethics committee/institutional review board approvals).

 -  A diagnosis of severe asthma, uncontrolled on GINA 4/5 asthma medication.

 -  Evidence of airway reversibility or airway hyper- reactivity.

 -  FEV1 of ≤80% of the predicted normal value for patients aged ≥18 years; FEV1 of ≤90%
 for patients aged 12 to <18 years

 -  An ACQ score ≥1.5.

 -  A history of 2 or more asthma exacerbations within the 12 months prior to entering the
 study.

 Exclusion Criteria:

 -  Use of other investigational drugs within 5 half-lives of study entry, or within 30
 days, whichever is longer.

 -  Subjects who have participated in another trial of QAW039.

 -  A QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female).

 -  History of malignancy with the exception of local basal cell carcinoma of the skin.

 -  Pregnant or nursing (lactating) women.

 -  Serious co-morbidities.

 -  Patients on greater than 20 mg of simvastatin, greater than 40 mg of atorvastatin,
 greater than 40 mg of pravastatin, or greater than 2 mg of pitavastatin