Investigating the Effects of QVM149 on MRI Ventilation Defects

A single site, two arm, randomized, open-label study in participants with asthma, who demonstrate visually obvious ventilation defects despite being on ICS/LABA was chosen to evaluate the capability of QVM149 150/50/160 μg once daily as compared to high dose dual therapy (ICS/LABA) to improve ventilation heterogeneity. According to the design of the study, hyperpolarized Xenon-129 (129Xe) will be used to measure ventilation defects in asthma participants as ventilation defect percent (VDP). A low-dose chest CT acquired within a few minutes of MRI will provide a way to measure both airway and parenchymal abnormalities. The selection of the QVM149 150/50/160 μg was made in order to keep the ICS dose equipotent to baseline therapy and to the active comparator arm and to directly compare the addition of a long-acting muscarinic antagonist (LAMA) versus continuing the therapy with high dose dual therapy (ICS/LABA). This study will be a single site, two arm, randomized, open-label study with the following treatment: * Treatment A: 2-week treatment with Indacaterol/Glycopyrronium/Mometasone 150/50/160 μg delivered as powder in hard capsules via Breezhaler, a breath-activated device which will deliver a specific dose of medication. * Treatment B: 2-week treatment with high dose dual therapy (ICS/LABA) in any approved drug formulation and delivery device. (Continue receiving high dose ICS/LABA therapy at the same dose and in the same formulation as at baseline). The study will consist of a screening/inclusion period of 1-5 days, followed by a treatment period of 14 days. The evaluation team including MRI observers will be blinded to treatment. At Visit 101, informed consent will be obtained before any study related assessments or procedures are performed. Asthma medications and eligibility criteria will be reviewed. Furthermore, at Visit 101, safety assessments including electrocardiography (ECG), hematology, blood chemistry, urinalysis, and spirometry to test reversibility will be performed. Once the above criteria are met, participants will move on to Visit 102. At Visit 102 all additional assessments, including MRI to detect visually obvious ventilation defects, low-dose chest CT, and Pulmonary Function Test assessments including spirometry, plethysmography, Lung Clearance Index (LCI) and Forced Oscillation Technique (FOT) will be conducted. Participants who qualify will then be randomized and entered into the 14 days treatment period and continue with the assessments according to study protocol. Participants will be supplied with open-label Indacaterol/Glycopyrronium/ Mometasone 150/50/160 μg o.d. delivered as powder in hard capsules via Breezhaler or continue with their previously prescribed high dose dual therapy (ICS/LABA) in any approved drug formulation and delivery device, which will be used during the study treatment period and stopped at Visit 201. Upon completion of the study treatment period at Visit 201, all participants will undergo post-treatment assessments, including MRI, pre- and post-salbutamol pulmonary function testing including spirometry, plethysmography, LCI, FOT, and asthma questionnaires. A final visit, Visit 301 will be scheduled for safety assessments. All participants will undergo vital signs, spirometry, ECG, bloodwork and urinalysis.