study of efficacy and safety of qaw039 in patients with severe asthma inadequately controlled with standard of care asthma treatment.

Conditions: Asthma

Summary: this study aimed to determine the efficacy and safety of qaw039 and qaw039 450 mg compared to 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 (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 and 450 mg) or placebo was added to 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 optional safety study (cqaw039a2315) directly after the week 52 study visit

Eligibility criteria:
inclusion criteria: * written informed consent. * male and female patients aged ≥12 years. * a diagnosis of severe asthma, uncontrolled on gina 4/5 asthma medication. * evidence of airway reversibility or airway hyper- reactivity. * fev1 ≤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 \>20 mg of simvastatin, \> 40 mg of atorvastatin, \>40 mg of pravastatin, or \>2 mg of pitavastatin.

Keywords: asthma qaw039