The purpose of this study is to evaluate the effectiveness of treatment with triple therapy an inhaler that contains three types of asthma medications, on participants with poorly controlled asthma. The triple therapy medication contains fluticasone furoate, an inhaled corticosteroid (ICS) which reduces inflammation in the lungs; umeclidinium (UMEC), a long-acting muscarinic antagonist (LAMA), a medication which helps open up the airways; and vilanterol (VI), a long-acting beta2-adrenergic agonist (LABA) which also helps open up airways, delivered in a single daily inhalation via an Ellipta inhaler. The Investigators will evaluate lung structure and function using magnetic resonance imaging (MRI). Participants will inhale xenon gas before an MRI image of their lungs is taken. Using a special technique xenon is visible in MRI images, so this lets us see how air spreads in the lungs. In healthy lungs, the gas fills the lungs evenly, but in unhealthy lungs, the gas may fill the lungs unevenly and they will appear patchy. The patchy areas are called ventilation defects. A CT of the chest will be done to assess the structure of the lungs. The Investigators will also be using lung function testing and questionnaires to compare them to MRI ventilation defect measurements.

This is an open-label, single arm pilot study in participants prescribed low or medium dose ICS/LABA inhaled therapy and poorly controlled asthma to quantify hyperpolarized 129Xe MRI VDP before and after six weeks of therapy with FF/UMEC/VI 200/62.5/25 ug QD. Male and females between 18 and 70 years of age will provide written informed consent to five visits including screening (Visit 1 week -2), baseline (Visit 2 week 0), mid-study Visit 3 in week 3, study end (Visit 4, week +6) and safety follow-up (Visit 5 week +8). The general study procedures are the same for Visit 1/Day -14, Visit 2/Day 0 and Visit 4/Day 42. Visit 3/Day 21 is an optional clinic visit or phone call. Visit 5 is a phone call check-in for adverse events.

For Visits 1, 2 and 4, participants are to withhold their medication as previously described. Vital signs will be recorded at the beginning of the visit. FeNO, spirometry, plethysmography, FOT, MBNW and 129Xe MRI will be performed pre-bronchodilator. FeNO will be performed before all other pulmonary function testing. Following 129Xe MRI, all participants will inhale 4 puffs (100mcg each) of a bronchodilator and quietly rest for 15 minutes. After 15 minutes, participants will undergo post-bronchodilator 129Xe MRI, and once MRI is complete, participants will undergo post-bronchodilator spirometry, plethysmography, FOT and MBNW. SGRQ, ACQ-6 and AQLQ will be administered after post-bronchodilator assessments are completed. For Visit 3, participants who choose to attend an in-person visit are to withhold their medication as described and the process for Visits 1, 2 and 4 will be followed. Participants who choose a phone call Visit 3 will be asked a series of questions regarding their breathing, asthma control and general health and they will complete the SGRQ, ACQ and AQLQ. For all participants, Visit 5 will entail a phone call check-in for adverse events. CT will be acquired at Visit 2, whilst MRI will be acquired on Visits 2, 4 and for those who prefer an in person visit, on Visit 3.

Inclusion Criteria:

• Participant understands study procedures and is willing to participate in the study as indicated by the participant's signature
• Provision of written, informed consent prior to any study specific procedures
• Males and females with a clinical diagnosis of eosinophilic asthma (based on FENO ≥40ppb, blood eosinophilia≥ 200 cells/μl at screening) aged 18 to 70 years, inclusively, at the time of Visit 1 (enrolment), under the care of a respirologist
• FEV1 ≥35 and ≤80% predicted
• Participant is a current non-smoker and non-vaper, having not smoked tobacco or cannabis, pipe or cigar or vaped any product for at least 12 months prior to the study with a tobacco smoking history of no more than 1 pack-year (i.e. 1 pack per day for 1 year).
• Women of childbearing potential (after menarche) must use a highly effective form of birth control (confirmed by the investigator or designee)
• A highly effective form of birth control includes true sexual abstinence, a vasectomized sexual partner, Implanon®, female sterilization by tubal occlusion, any effective intrauterine device (IUD)/levonorgestrel intrauterine system (IUS), Depo-ProveraTM injections, oral contraceptive and Erva PatchTM or NuvaringTM
• Women of childbearing potential (after menarche) must agree to use a highly effective form of birth control, as defined above, from enrolment, throughout the study duration, and 8 weeks after last dose of study drug, with negative pregnancy test result at Visit 1
• Male participants who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of the study drug until 8 weeks after last dose
• Participant has documented treatment with a stable dose of low to medium dose inhaled corticosteroids (defined as >250 and ≤500 mcg fluticasone proprionate/day or equivalent or, >400 to ≤800 mcg Budesonide/day for at least 6 months prior to enrolment
• long-acting β2-agonist (LABA) for at least 6 months prior to enrolment
• Participant has blood eosinophils ≥ 200 cells/μl or FENO ≥25ppb at Visit 1 for all participants except for those with previous biologic therapy without washout who will be required to washout prior to screening.
• Participant has ACQ-6 ≥ 1.5 at visit 1
• Participant has a history of poorly controlled asthma (i.e. ≥ 2 exacerbations in past 24 months)

Exclusion Criteria:

• Participant is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand written material
• Participant has clinically important pulmonary disease other than asthma (e.g. active lung infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha-1 antitrypsin deficiency and primary ciliary dyskinesia) or been diagnosed with pulmonary or systemic disease other than asthma that is associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome), except for those atopic conditions that can be associated with asthma (e.g. allergic rhinitis, sinusitis with or without polyposis, eczema, and eosinophilic esophagitis)
• Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Qualified Investigator and/or could affect the safety of the participant throughout the study, influence the findings of the study or their interpretations, or impede the participant's ability to complete the entire duration of the study, as assessed by the Qualified Investigator.
• Known history of allergy or reaction to the study drug formulation
• Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date of informed consent
• Clinically significant asthma exacerbation, defined as a change from baseline deemed clinically relevant in the opinion of the Qualified investigator, including those requiring the use of OCS, or an increase in maintenance dosage of OCS within 30 days prior to the date of informed consent. Participants with an exacerbation after providing informed consent but prior to treatment start will be excluded from the study
• Receipt of immunoglobulin or blood products within 30 days prior to the date of informed consent
• Receipt of live attenuated vaccines 30 days prior to the date of enrolment
• Previously randomized in any FF/UMEC/VI 200/62.5/25ug study
• Planned surgical procedure during the conduct of the study
• Concurrent enrolment in another clinical trial
• Participant has history of alcohol or drug abuse within 12 months prior to the date of informed consent
• Participant is a female who is ≤8 weeks post-partum or breast feeding an infant
• Participant is pregnant, or intends to become pregnant during the time course of the study
• Participant is unable to perform MRI breath-hold maneuver
• Participant is unable to perform spirometry maneuver
• Participant is hospitalized or has had a major surgical procedure, major trauma requiring medical attention, or significant illness requiring medical attention within 4 weeks of Visit 1
• Participant has a blood pressure of >150 mmHg systolic or >95 mmHg diastolic on more than 2 measurements done >5 minutes apart at Visit 1
• In the opinion of the investigator, participant suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia
• Participant has implanted mechanically, electrically or magnetically activated device or any metal in their body, which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) - at the discretion of the MRI Technologist.

All enrolled, Completed Visit 1

9 Months