A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of QAW039 When Added to Existing Asthma Therapy in Patients With Uncontrolled Severe Asthma.
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 877
- Locations
- 1
- Primary Endpoint
- Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation
Overview
Brief 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)
Detailed Description
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 QAW
- •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.
Arms & Interventions
QAW039 150 mg
QAW039 150 mg once daily
Intervention: QAW039 (Drug)
QAW039 450 mg
QAW039 450 mg once daily
Intervention: QAW039 (Drug)
Placebo
Placebo once daily
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation
Time Frame: 52 weeks
A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours\*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall Population
Time Frame: 52 weeks
A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours\*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours).
Secondary Outcomes
- Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in High Eosinophils Subpopulation(Baseline, Week 52)
- Change From Baseline to Week 52 in Asthma Control Questionnaire-5 (ACQ-5) Score in High Eosinophils Subpopulation(Baseline, Week 52)
- Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in High Eosinophils Subpopulation(Baseline, Week 52)
- Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in Overall Population(Baseline, Week 52)
- Change From Baseline to Week 52 in Asthma Control Questionnaire-5 (ACQ-5) Score in Overall Population(Baseline, Week 52)
- Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in Overall Population(Baseline, Week 52)