Study of Safety of QAW039 in Patients With Asthma Inadequately Controlled on Standard-of-care Asthma Treatment

Study Overview
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Brief Summary
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This study was a 2-treatment period, randomized, multicenter parallel-group study. The overall purpose of this study was to provide long- term safety data for fevipiprant (QAW039) (Dose 1 and Dose 2), compared with placebo, when added to the Global Initiative for Asthma (GINA) steps 3, 4, and 5 standard-of-care (SoC) asthma therapy (GINA 2016), in patients with moderate-to- severe asthma. The purpose of this study was to provide long-term safety data for QAW039 150 mg once daily and 450 mg once daily, compared with placebo, when added to GINA steps 3, 4, and 5 standard-of-care asthma therapy (GINA 2020) in adult and adolescent (≥12 years) patients with moderate-to-severe asthma. The study included 2 cohorts of patients: Rollover patients who had completed any of the four Phase 3 pivotal efficacy studies with QAW039 (QAW039A2307, QAW039A2314, QAW039A2316, or QAW039A2317, hereafter referred to as Studies A2307, A2314, A2316, and A2317), thus providing data for a longer duration of exposure, and New patients who had not previously participated in a study of QAW039, permitting an increase in the number of patients with long-term exposure to QAW039. By including these 2 categories of patients, the total number of patients treated with QAW039 as well as the duration of exposure to QAW039 treatment was substantially increased, supporting evaluation of the safety profile of QAW039.

Detailed Description
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The study comprised 2-treatment period. Treatment Period 1 was a 52-week, double-blind treatment period in which QAW039 450 mg or 150 mg or placebo was added to standard-of-care asthma therapy according to GINA guidelines. Treatment Period 2 was an optional 104-week, single-blind treatment period in which patients received QAW039 450 mg or 150 mg or placebo added to standard-of-care asthma therapy according to GINA guidelines.

Official Title
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A 2-treatment Period, Randomized, Placebo-controlled, Multicenter Parallel-group Study to Assess the Safety of QAW039 When Added to Existing Asthma Therapy in GINA Steps 3, 4 and 5 Patients With Uncontrolled Asthma.

Conditions
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Asthma

Intervention / Treatment
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* Drug: QAW039 150 mg
* Drug: QAW039 450 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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: Written informed consent. A diagnosis of asthma,uncontrolled on GINA 3/4/5 asthma medication. Evidence of airway reversibility or airway hyper- reactivity. FEV1 of ≤85% of the predicted normal value. An ACQ score ≥1.5 prior to entering the study. Exclusion Criteria: Patients completing a prior phase 3 study of QAW039: Pregnant or nursing (lactating) women. Women of child-bearing potential 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 QAW039 study they participated in. Inability to comply with all study requirements. Patient who experienced a serious and drug-related AE in the prior QAW039 study they participated in. Patients who have not previously participated in a study of QAW039: 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 QAW039 (i.e.-the patient was randomized in another study). 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 greater than 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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QAW039 150mg<br>QAW039 Dose 1 once daily | Drug: QAW039 150 mg<br>* One tablet of QAW039 150 mg once daily<br>|
| Experimental: QAW039 450 mg<br>QAW039 Dose 2 once daily | Drug: QAW039 450 mg<br>* One tablet of QAW039 450 mg once daily<br>|
| Placebo Comparator: Placebo<br>Placebo once daily | Drug: Placebo<br>* One tablet of Placebo once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 52 - Cox Regression Model | Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs. For this Outcome Measure, AE up to week 52 are reported. | 52 weeks | 
| Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 156 - Cox Regression Model | Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs | 156 weeks | 
| Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 52 - Cox Regression Model | Serious Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +30 days were classified as treatment emergent SAEs. For this Outcome Measure, AE up to week 52 are reported. | 52 weeks | 
| Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 156 - Cox Regression Model | Serious Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +30 days were classified as treatment emergent SAEs. | 156 weeks | 
| Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 52 - Cox Regression Model | Adverse events leading to study treatment discontinuation starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs leading to study treatment discontinuation. For this Outcome Measure, AE up to week 52 are reported. | 52 weeks | 
| Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 156 - Cox Regression Model | Adverse events leading to study treatment discontinuation starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs leading to study treatment discontinuation | 156 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model | The number of patients per patient year of follow-up having a treatment emergent adverse event, categorized by system organ class. Treatment emergent adverse events are defined as an AEs starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) | 52 weeks | 
| Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model | The number of patients per patient year of follow-up having a treatment emergent adverse event, categorized by system organ class. Treatment emergent adverse events are defined as an AEs starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) | 156 weeks | 
| Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 52 | The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs. | 52 weeks | 
| Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 156 | The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs. | 156 weeks | 
| Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 52 | Number of treatment emergent severe asthma exacerbation episodes requiring hospitalizations (any visit to the hospital requiring an overnight stay or an emergency room visit greater than 24 hours) per person year of follow-up. Treatment emergent severe asthma exacerbation episodes are defined as episodes occurring on or after the day of the first intake of study drug and until the day of last intake of study drug +7 days (30 days in the case of a serious AE). Rate of exacerbations per person year = total number of exacerbations / total number of treatment years | 52 weeks | 
| Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 156 | Number of treatment emergent severe asthma exacerbation episodes requiring hospitalizations (any visit to the hospital requiring an overnight stay or an emergency room visit greater than 24 hours) per person year of follow-up. Treatment emergent severe asthma exacerbation episodes are defined as episodes occurring on or after the day of the first intake of study drug and until the day of last intake of study drug +7 days (30 days in the case of a serious AE). Rate of exacerbations per person year = total number of exacerbations / total number of treatment years | 156 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, QAW039, allergic asthma, allergy triggered asthma, reactive asthma, asthma attack, difficulty breathing