Asthma
Conditions
Keywords
QAW039, uncontrolled asthma
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.
Interventions
DRUGQAW039
QAW039 once daily
DRUGPlacebo
Placebo once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pre-dose FEV1 | Baseline and Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daytime Asthma Symptom Score | Baseline and Week 12 | 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. |
| Change From Baseline in Number of Puffs of SABA Taken Per Day | Baseline (daily mean for up to three weeks prior to baseline visit) and Week 12 (daily mean post baseline up to Week 12) | 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. |
| Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Score | Baseline and Week 12 | 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. |
Countries
Brazil, Bulgaria, Canada, Colombia, Germany, Hungary, India, Israel, Italy, Peru, Puerto Rico, Russia, South Korea, Spain, Sweden, Tunisia, United States, Vietnam
Participant flow
Recruitment details
Participants were recruited from centers in Brazil (8), Bulgaria (4), Canada (3), Colombia (4), Germany (5), Hungary (7), India (5), Israel (5), Italy (4), Peru (6), Republic of Korea (5), Russian Federation (14), Spain (8), United States (36), Vietnam (3).
Participants by arm
| Arm | Count |
|---|---|
| QAW039 QAW039 150mg once daily | 352 |
| Placebo Placebo once daily | 350 |
| Total | 702 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Subject/Guardian Decision | 7 | 6 |
| Overall Study | Technical Problems | 0 | 2 |
Baseline characteristics
| Characteristic | QAW039 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50.4 Years STANDARD_DEVIATION 14.87 | 50.2 Years STANDARD_DEVIATION 14.39 | 50.3 Years STANDARD_DEVIATION 14.62 |
| Race/Ethnicity, Customized Asian | 41 Participants | 46 Participants | 87 Participants |
| Race/Ethnicity, Customized Black | 26 Participants | 18 Participants | 44 Participants |
| Race/Ethnicity, Customized Caucasian | 216 Participants | 216 Participants | 432 Participants |
| Race/Ethnicity, Customized Native American | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Other | 55 Participants | 58 Participants | 113 Participants |
| Race/Ethnicity, Customized Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 216 Participants | 218 Participants | 434 Participants |
| Sex: Female, Male Male | 136 Participants | 132 Participants | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 352 | 0 / 350 |
| other Total, other adverse events | 94 / 352 | 116 / 350 |
| serious Total, serious adverse events | 7 / 352 | 3 / 350 |
Outcome results
Primary
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.
Time frame: Baseline and Week 12
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study medication. Patients in the FAS were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QAW039 | Change From Baseline in Pre-dose FEV1 | 0.126 Liters | Standard Error 0.00177 |
| Placebo | Change From Baseline in Pre-dose FEV1 | 0.157 Liters | Standard Error 0.0177 |
p-value: 0.21495% CI: [-0.08, 0.018]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study medication. Patients in the FAS were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QAW039 | Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Score | 0.77 units on a scale | Standard Error 0.043 |
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Score | 0.72 units on a scale | Standard Error 0.043 |
p-value: 0.44895% CI: [-0.07, 0.17]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study medication. Patients in the FAS were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QAW039 | Change From Baseline in Daytime Asthma Symptom Score | -0.55 Score | Standard Error 0.034 |
| Placebo | Change From Baseline in Daytime Asthma Symptom Score | -0.45 Score | Standard Error 0.034 |
p-value: 0.0350.035% CI: [-0.19, 0.01]ANCOVA
Secondary
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.
Time frame: Baseline (daily mean for up to three weeks prior to baseline visit) and Week 12 (daily mean post baseline up to Week 12)
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study medication. Patients in the FAS were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QAW039 | Change From Baseline in Number of Puffs of SABA Taken Per Day | -0.89 Puffs per day | Standard Error 0.066 |
| Placebo | Change From Baseline in Number of Puffs of SABA Taken Per Day | -0.88 Puffs per day | Standard Error 0.066 |
p-value: 0.89395% CI: [-0.2, 0.17]ANCOVA