Study of Efficacy and Safety of QAW039 When Added to Standard-of-care Asthma Therapy in Patients With Uncontrolled Asthma

Study Overview
=================
Brief Summary
-----------------
A randomized, multicenter, double-blind, placebo- controlled parallel-group study to determine the efficacy and safety of QAW039, compared with placebo, when added to standard-of-care (SoC) asthma therapy in adult and adolescent (≥ 12 years) patients with uncontrolled asthma with respect to change from baseline in forced expiratory volume in 1 second (FEV1) at the end of 12 weeks of treatment.

Official Title
-----------------
A 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of QAW039 When Added to Standard-of-care Asthma Therapy in Patients With Uncontrolled Asthma

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: QAW039
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A diagnosis of asthma (according to GINA 2016) for a period of at least 6 months. Treated with medium dose inhaled corticosteroid (ICS), or high dose ICS, or low dose ICS plus long- acting beta agonist (LABA), or low dose ICS plus leukotriene receptor antagonist (LTRA), or medium dose ICS plus LABA for at least 3 months prior to Visit 1 and the doses have been stable for at least 4 weeks prior to Visit 1. FEV1 of ≤85% for patients aged ≥18 years. FEV1 of ≤90% for patients aged 12 to <18 years. Daytime asthma symptom score (0 to 6 scale) of ≥1 per day during 4 of the last 7 days of the placebo run- in period. Total daily SABA use ≥1 puff per day during 4 of the last 7 days of the placebo run-in period. Demonstrated reversible airway obstruction. Asthma control questionnaire (ACQ) score ≥ 1.5. Exclusion Criteria: Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days, whichever is longer. A resting QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female). 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. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: QAW039<br>QAW039 once daily | Drug: QAW039<br>* QAW039 once daily<br>|
| Placebo Comparator: Placebo<br>Placebo once daily | Drug: Placebo<br>* Placebo once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pre-dose FEV1 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Daytime Asthma Symptom Score | Daytime asthma symptoms are evaluated through four questions and each of them will be rated on a scale of 0 to 6. Higher scores indicate more severe asthma-related symptoms. A mean score is calculated for the responses to 4 questions. | Baseline and Week 12 | 
| Change From Baseline in Number of Puffs of SABA Taken Per Day | Daily use of SABA (the number of rescue medication puffs taken in the previous 12 hours) was recorded using a patient electronic diary (referred to as eDiary or eDiary/ePEF). Patients were instructed to routinely complete the patient diary twice daily - at the same time each morning and each evening, approximately 12 hours apart. | Baseline (daily mean for up to three weeks prior to baseline visit) and Week 12 (daily mean post baseline up to Week 12) | 
| Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Score | AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated better quality of life. Overall AQLQ+12 score is the mean of all 32 responses. | Baseline and Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
QAW039, uncontrolled asthma