asthma

Treatment Period 1 (double-blind, 52-week treatment period): In patients with moderate-to-severe asthma receiving SoC asthma therapy, to evaluate the long-term safety of QAW039 (150 mg once daily and 450 mg once daily), compared with placebo. Treatment Period 1 and Treatment Period 2 combined: In patients with moderate-to-severe-asthma receiving SoC asthma therapy, to evaluate the long-term safety of QAW039 (150 mg once daily and 450 mg once daily), compared with placebo.

QAW039

QAW039 (Fevipiprant)

Tablet

150, 450

Treatment Period 1 (double-blind, 52-week treatment period):
 treatment emergent adverse events (AEs);
 treatment emergent serious adverse events (SAEs); and
 study treatment discontinuations due to treatment emergent AEs.

Treatment Period 1 and Treatment Period 2 combined:
 treatment emergent AEs
 treatment emergent SAEs; and
 study treatment discontinuations due to treatment emergent AEs.

Patients completing a prior Phase 3 study of QAW039:
 Informed consent and assent (if applicable).
 Completion of the Treatment Period (on blinded study drug) of a prior
Phase 3 study of QAW039.
 Patient is able to safely continue into the study as judged by the
investigator.
Patients who have not previously participated in a study of QAW039:
 Informed consent and assent (if applicable).
 Male and female patients at a minimum age of 12 years (or higher
minimum age limit as allowed by health authority and/or ethics
committee/institutional review board (IRB) approvals)
 A diagnosis of asthma (according to GINA 2016) for a period of at least
24 months prior to Screening visit (Visit 1).
 Patients have been treated with GINA steps 4 or 5 standard-of-care
(SoC) asthma therapy for at least 3 months prior to Visit 1. The doses
must have been stable for at least 4 weeks prior to Visit 1.
 Demonstration of inadequate control of asthma based on an Asthma
Control Questionnaire (ACQ) score ≥1.5 at Visit 1.
 For patients aged ≥18 years, forced expiratory volume in the first
second (FEV1) of ≤85% of the predicted normal value for the patient,
after withholding bronchodilators at Visit 1.
 For patients aged 12 to <18 years, FEV1 of ≤90% of the predicted
normal value for the patient, after withholding bronchodilators at Visit 1.
 A clinical diagnosis of asthma supported by at least one of the
following:
 An increase of ≥12% and ≥200 ml in FEV1 approximately 10 to 15
minutes after administration of 400 mcg of salbutamol/albuterol (or
equivalent dose) prior to randomization. Spacer devices are not
permitted during reversibility testing. All patients must perform a
reversibility test at Visit 1.
If reversibility is not demonstrated at Visit 1, the following historical
information may be used:
 Documented evidence of reversibility performed according to
American Thoracic Society/European Respiratory Society
(ATS/ERS) (ATS/ERS 2005) or country-specific guidelines within
the 2 years prior to Visit 1.
 Documented evidence of a positive airways hyper-responsiveness
(AHR) test result within the 2 years prior to Visit 1, defined as a
provoked fall in FEV1 of 20% by methacholine at ≤8 mg/ml (or
histamine ≤10 mg/ml or acetylcholine <20 mg/mL) when not on
ICS or ≤16 mg/ml (or histamine ≤20 mg/ml or acetylcholine <40
mg/mL) on ICS therapy performed according to ATS/ERS
guidelines.

Patients completing a prior phase 3 study of QAW039:
 Pregnant or nursing (lactating) women.
 Women of child-bearing potential, defined as all women physiologically
capable of becoming pregnant, unless they are using basic methods of
contraception during dosing of study drug.
 Patients who did not complete the Treatment Period on blinded study
drug of the prior phase 3 study of QAW039 they participated in.
 Inability to comply with all study requirements.
 Patients who experienced a serious and drug-related AE in the prior
phase 3 study of QAW039 they participated in.
Patients who have not previously participated in a study of QAW039:
 Use of other investigational drugs within 5 half-lives of enrollment, or
within 30 days, whichever is longer.
 Patients who have participated in another trial of QAW039 (i.e., the
patient was randomized into another study of QAW039).
 Patients with a resting QTcF (Fridericia) ≥450 msec (male) or ≥460
msec (female) at Visit 1 or Visit 201 on the ECG Analysis Report
provided by the ECG core laboratory.
 Use of agents known to prolong the QT interval unless it can be
permanently discontinued for the duration of the study.
 History of malignancy of any organ system (other than localized basal
cell carcinoma of the skin or in situ cervical cancer), treated or
untreated, within the past 5 years, regardless of whether there is
evidence of local recurrence or metastases.
 Pregnant or nursing (lactating) women.
 Women of child-bearing potential, defined as all women physiologically
capable of becoming pregnant, unless they are using basic methods of
contraception during dosing of study drug.
 Patients who have a clinically significant laboratory abnormality at the
Visit 1 laboratory test.
 Patients on >20 mg of simvastatin, > 40 mg of atorvastatin, >40 mg of
pravastatin, or >2 mg of pitavastatin. Statin doses less than or equal to
these doses as well as other statins will be permitted during the study.
 Patients on rifampin, probenecid, ritonavir and valproic acid (i.e.,
medications blocking several pathways important for the elimination of
QAW039 [broad range UDP-glucuronosyltransferase (UGT) inhibition
and/or inhibition of organic anion transporters (OAT3), OATP1B3,
multixenobiotic resistance (MXR) and p glycoprotein (P-gp)].