Introduction
Methods
Liberty Asthma QUEST Study Design
Key inclusion criteria
|
Adults and adolescent pts (≥ 12 years) |
Physician-diagnosed asthma for ≥ 12 months, based on GINA 2017 Guidelines [23] |
Existing treatment with medium-to-high-dose ICS (≥ 250 μg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 μg/day of fluticasone propionate or equivalent) in combination with a second controller (e.g., LABA, LTRA) for at least 3 months with a stable dose ≥ 1 month prior to visit 1 |
Pre-bronchodilator FEV1 ≤ 80% of predicted normal for adults and ≤ 90% of predicted normal for adolescents at visits 1 and 2, prior to randomization |
ACQ-5 score ≥ 1.5 at visits 1 and 2, prior to randomization |
Reversibility of at least 12% and 200 mL in FEV1 after the administration of 200–400 μg albuterol/salbutamol or levalbuterol/levosalbutamol before randomization |
Must have experienced, within 1 year prior to visit 1, any of the following events: |
Treatment with a systemic steroid (oral or parenteral) for worsening asthma at least once |
Hospitalization or emergency medical care visit for worsening asthma |
Key exclusion criteria
|
Pts < 12 years of age or the minimum legal age for adolescents in the country of the investigative site, whichever is higher |
Weight is less than 30 kg |
Diagnosis of chronic obstructive pulmonary disease or other lung disease that may impair lung function |
Evidence of lung disease(s) other than asthma, either clinical evidence or imaging (e.g., chest X-ray, CT, MRI), within 12 months of visit 1 as per local standard of care |
A severe asthma exacerbation at any time from 1 month before screening up to and including the baseline visit |
Current smokers, or smokers who stopped within 6 months before screening or had a previous smoking history of > 10 pack-years |
Anti-IgE therapy within 130 days before screening or any other biologic therapy/immunosuppressant within 2 months (or five half-lives) before screening |
Exposure to another investigative antibody within five half-lives or 6 months before screening, or to any other (non-antibody) investigative agent within 30 days before screening |
Comorbid disease that might interfere with the evaluation of dupilumab |
Previous treatment with dupilumab |
Treatment/Dosing
Objectives and Outcome Measures
Outcome measure | Time frame |
---|---|
Primary efficacy endpoints
| |
Annualized rate of severe exacerbation events | 52 weeks |
Absolute change from baseline in pre-bronchodilator FEV1 | Week 12 |
Secondary efficacy endpoints
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Percentage change from baseline in pre-bronchodilator FEV1a | Week 12 |
Annualized rate of severe exacerbation events in pts with ≥ 300 or ≥ 150 eosinophils/μL | Week 12 |
Absolute change from baseline in pre-bronchodilator FEV1 in pts with ≥ 300 or ≥ 150 eosinophils/μL | Week 12 |
Absolute change from baseline in pre-bronchodilator FEV1 | Weeks 2, 4, 8, 24, 36, 52 |
Percentage change from baseline in pre-bronchodilator FEV1 | Weeks 2, 4, 8, 24, 36, 52 |
Annualized rate of severe exacerbation events in pts with ≥ 300 eosinophils/μL | 52 weeks |
Absolute change from baseline in pre-bronchodilator FEV1 in pts with ≥ 300 eosinophils/μL | Week 12 |
Percentage change from baseline in pre-bronchodilator FEV1 in pts with ≥ 300 eosinophils/μL | Week 12 |
Annualized rate of severe exacerbation events in pts with ≥ 150 eosinophils/μL | 52 weeks |
Absolute change from baseline in pre-bronchodilator FEV1 in pts with ≥ 150 eosinophils/μL | Week 12 |
Percentage change from baseline in pre-bronchodilator FEV1 in pts with ≥ 150 eosinophils/μL | Week 12 |
Annualized rate of severe exacerbation events in pts on high-dose ICS | 52 weeks |
Absolute change from baseline in pre-bronchodilator FEV1 in pts on high-dose ICS | Week 12 |
Percentage change from baseline in pre-bronchodilator FEV1 in pts on high-dose ICS | Week 12 |
Change from baseline in other lung function measurementsb | Weeks 2, 4, 8, 12, 24, 36, 52 |
Annualized rate of loss of asthma control event | 52 weeks |
Annualized rate of severe exacerbation events resulting in hospitalization or ER visit | 52 weeks |
Time to first severe exacerbation event | 52 weeks |
Time to first loss of asthma control event | 52 weeks |
Change from baseline in ACQ-5 and ACQ-7 score | Weeks 2, 4, 8, 12, 24, 36, 52 |
Change from baseline in am/pm asthma symptom score and nocturnal awakenings | Weeks 2, 4, 8, 12, 24, 36, 52 |
Change from baseline in rescue medication use | Weeks 2, 4, 8, 12, 24, 36, 52 |
Change from baseline in healthcare resource utilization | Weeks 12, 24, 36, 52 |
Change from baseline in PROs (AQLQ, EQ-5D-5L, HADS, SNOT-22c, RQLQd) | Weeks 12, 24, 36, 52 |
Other endpoints
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Systemic drug concentration and anti-drug antibodies | Weeks 12, 24, 36, 52 |
Biomarker assessment (FeNO, blood eosinophils, periostin, TARC, IgE, ECP, eotaxin-3) | Weeks 12, 24, 36, 52 |
Safety and tolerability (includes AEs, vital signs, physical exam, clinical labs, ECG) | Continuous |
Statistical Considerations
Subgroup | Criteria |
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Age group (years) | < 18, 18–64, ≥ 65; < 18, ≥ 18 |
Gender | Male, female |
Region | Asia: Japan, South Korea, and Taiwan; Latin America: Argentina, Brazil, Colombia, Chile, and Mexico; East Europe: Hungary, Poland, Russia, Turkey, and Ukraine; Western countries: Australia, Canada, France, Germany, Italy, South Africa, Spain, UK, and USA |
Territory | North America: Canada and USA; European Union: France, Germany, Hungary, Italy, Poland, Spain, and UK; Rest of world: Argentina, Australia, Brazil, Colombia, Chile, Japan, Mexico, Russia, South Africa, South Korea, Taiwan, Turkey, and Ukraine |
Race/ethnicity | Caucasian/White, Black/of African descent, Asian/Oriental, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, Other |
Baseline blood eosinophil level (cells/μL) | ≥ 300, < 300; ≥ 150, < 150 |
Background ICS dose levels at randomization | Medium, high |
Background controller type at randomization | ICS and LABA only, ICS and LABA and anti-leukotrienes only; ICS, LABA, and any third controller, other |
Baseline FEV1 (L) | ≤ 1.75, > 1.75 |
ACQ-5 | ≤ 2, > 2 |
Number of severe asthma exacerbations prior to the study | 1, > 1 |
Baseline weight (kg) | < 60, ≥ 60, < 70, ≥ 70, < 90, ≥ 90 |
Baseline BMI (kg/m2) | < 25, 25 to < 30, ≥ 30 |
Smoking history | Former, never |
Atopic medical condition | Yes, no |
Age at onset of asthma (years) | < 18, 18–40, > 40 |
Baseline predicted FEV1 (%) | < 60, 60–90 |
Baseline periostin (ng/mL) | < Median, ≥ median |
Baseline FeNO (ppb) | < 25, ≥ 25 to < 50, ≥ 50 |