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

Phase 3

Terminated

• Conditions: Asthma
• Interventions: Drug: QAW039 150 mg; Drug: QAW039 450 mg; Drug: Placebo

• Registration Number: NCT03052517
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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:

1. 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

2. 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

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.

Study Timeline

• Study First Submitted: 2017-01-23
• Study First Submitted QC: 2017-02-09
• Study First Posted: 2017-02-14
• Study Start: 2017-03-21
• Primary Completion: 2020-02-19
• Study Completion: 2020-03-16
• Status Verified: 2020-09
• Results First Submitted: 2020-09-14
• Results First Submitted QC: 2020-09-14
• Last Update Submitted: 2020-09-14
• Results First Posted: 2020-10-12
• Last Update Posted: 2020-10-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2538

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QAW039 150mg	QAW039 150 mg	QAW039 Dose 1 once daily
QAW039 450 mg	QAW039 450 mg	QAW039 Dose 2 once daily
Placebo	Placebo	Placebo once daily

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 52 - Cox Regression Model	52 weeks	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.
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 156 - Cox Regression Model	156 weeks	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.
Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 52 - Cox Regression Model	52 weeks	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.
Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 156 - Cox Regression Model	156 weeks	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
Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 52 - Cox Regression Model	52 weeks	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.
Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 156 - Cox Regression Model	156 weeks	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

Secondary Outcome Measures

Name	Time	Method
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model	52 weeks	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)
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model	156 weeks	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)
Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 52	52 weeks	The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs.
Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 156	156 weeks	The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs.
Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 52	52 weeks	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
Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 156	156 weeks	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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Leicester, United Kingdom