A Long-term Safety Study of QVM149 in Japanese Patients With Asthma

Study Overview
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Brief Summary
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The purpose of this study is to provide long term safety data of QVM149 in Japanese patients with asthma for the registration of QVM149 in Japan.

Official Title
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A Multicenter, Open-label, Single Arm, 52-week Treatment Study to Assess the Safety of QVM149 in Japanese Patients With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: QVM149


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Male and female adult patient ≥ 18 years old. Patients with a diagnosis of persistent asthma (GINA 2016) for a period of at least 1 year prior to Visit 1. Patients who have used medium or high dose of ICS/LABA combinations for asthma for at least 3 months and at stable dose and regimen for at least 4 weeks prior to Visit 1. An ACQ-7 score ≥ 1.5 at Visits 2. Pre-bronchodilator FEV1 of ≥ 40% and ≤ 85% of the predicted normal value for the patient after withholding bronchodilators at Visit 2. o Repeating is allowed once only. Repeating of percentage predicted FEV1 should be done in an ad-hoc visit to be scheduled on a date that would provide sufficient time to receive confirmation from the spirometry data central reviewer of the validity of the assessment before Visit 99. Patients must demonstrate reversibility defined as an increase in FEV1 of ≥ 12% and 200 mL within 15 to 30 minutes after administration of 400 µg of salbutamol at Visit 2. Spacer devices are permitted during reversibility testing only. The Investigator or delegate may decide whether or not to use a spacer for the reversibility testing. If reversibility is not proven at Visit 2, patients may be permitted to enter the study with historical evidence of reversibility that was performed within 5 years prior to Visit 1. Alternatively, patients may be permitted to enter the study with a historical positive bronchoprovocation test (defined as a provoked fall in FEV1 of 20% by bronchoconstriction agent e.g., methacholine, histamine) or equivalent test (e.g., astography) that was performed within 5 years prior to Visit 1. If reversibility is not proven at Visit 2 and historical data is not available, reversibility should be repeated once in an ad-hoc visit scheduled as close as possible from the first attempt (but not on the same day). Exclusion Criteria: Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6-weeks of Visit 1. Patients who have ever required intubation for a severe asthma attack/exacerbation. Patients who have a clinical condition which is likely to be worsened by ICS administration (e.g. glaucoma, cataract and fragility fractures) who are according to investigator's medical judgment at risk participating in the study. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder-neck obstruction or severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered. Patients who have had a respiratory tract infection or asthma worsening as determined by investigator within 4 weeks prior to Visit 1 or between Visit 1 and Visit 99. Patients may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening. Patients with a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis. Patients with severe narcolepsy and/or insomnia Pregnant or nursing (lactating) women Women of child-bearing potential unless they are using highly effective methods of contraception during dosing and for 30 days after stopping of investigational medication

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QVM149<br>All eligible patients take QVM149 150/50/160 μg once daily over 52 weeks. | Drug: QVM149<br>* QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate)<br>* Other names: QVM149 150/50/160 μg once daily, delivered as powder in hard capsules via Concept1 inhaler;|

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 (TEAEs), Serious Adverse Events (SAEs) | An adverse event (AE) was any untoward medical occurrence (example; any unfavorable and unintended sign including abnormal laboratory findings, symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study until the end of study visit. TEAEs were defined as adverse events started on or after the time of the first inhalation of study drug but no later than 7 days after the last administration (30 days in the case of SAEs). SAE was defined as any adverse event (appearance of [or worsening of any pre-existing]) undesirable sign, symptom or medical conditions which is fatal or life-threatening or results in persistent or significant disability/incapacity or constitutes a congenital anomaly/birth defect or requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant. | Up to 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Pre-dose) Forced Expiratory Volume in One Second (FEV1) at Week 26 and 52 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Change from baseline in FEV1 at week 26 and 52 was reported. | Baseline (Pre-dose), Week 26, Week 52 | 
| Change From Baseline (Pre-dose) Forced Vital Capacity (FVC) at Week 26 and 52 | Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry. Change from baseline in FVC at week 26 and 52 was reported. | Baseline (Pre-dose), Week 26, Week 52 | 
| Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF) Over 52 Weeks | PEF is the peak expiratory flow, the maximum speed of expiration. Electronic peak flow meter (ePEF) was given to each participant at visit 1 for the measurement of morning and evening PEF. Change from baseline in morning and evening PEF over 52 weeks was measured. | Baseline up to week 52 | 
| Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 26 and 52 | ACQ-7 is a 7-item, disease-specific instrument developed and validated to assess asthma control in participants. All 7 items were scored on a 7-point Likert scale, with 0 indicating total control of asthma and 6 indicating poor control of asthma. The questions were equally weighted and the total score is the mean of the 7 items. A decrease of ACQ-7 score of at least 0.5 from baseline was considered to be clinically meaningful improvement. | Baseline, Week 26, Week 52 | 
| Proportion of Participants Who Achieved Clinically Meaningful Improvement Threshold in ACQ-7 Score (Decrease of Greater Than or Equal to 0.5 Units in ACQ-7) at Week 26 and 52 | ACQ-7 is a 7-item, disease-specific instrument developed and validated to assess asthma control in participants. All 7 items were scored on a 7-point likert scale, with 0 indicating total control of asthma and 6 indicating poor control of asthma. Questions were equally weighted and total score is mean of 7 items. A decrease from baseline of at least 0.5 units in ACQ-7 score was considered to be clinically meaningful improvement. The proportion of participants achieving the clinically meaningful improvement threshold in ACQ-7 score were reported at Week 26 and Week 52. | Week 26, Week 52 | 
| Change From Baseline in Daily Number of Puffs of Rescue Medication Over 52 Weeks | Daily use of rescue medication (number of puffs taken in the previous 12 hours) were recorded each morning and evening throughout the 52 week treatment by the participant using their electronic diary. | Baseline up to week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QVM149, Asthma, Japanese, Allergic asthma, Allergy triggered asthma, Reactive asthma, Asthma attack, Difficulty breathing