Evaluation of Triple Therapy Using Magnetic Resonance Imaging in Asthma

NCT04651777 | Active Not Recruiting Phase 3 Results

• 1 other identifier: ROB0046
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma

Keywords

Fluticasone furoate; umedlidinium; Vilanterol; Triple Therapy; Xenon

Outcome Measures

Primary Outcomes (1)

• Change From Baseline Airway Function Measured Using 129-Xenon MRI Ventilation Defect Percent at the End of 6 Weeks of Treatment With FF/UMEC/VI 200/62.5/25ug Once Daily

  Change in VDP

  Day 0 to day 42

Secondary Outcomes (9)

• Change From Baseline Forced Expiration Volume in One Second

  Baseline and Day 42

• Change From Baseline Forced Vital Capacity

  Baseline and Day 42

• Change From Baseline Residual Volume

  Baseline and Day 42

• Change From Baseline Total Lung Capacity

  Baseline and Day 42

• Change From Baseline in Proximal Airway Reactance at 5 Hz (R5), 19 Hz (R19), and 5 Hz - 19 Hz (R5-19)

  Baseline and Day 42

Study Arms (1)

Participants with poorly controlled moderate to severe asthma

EXPERIMENTAL

Participants with poorly controlled moderate to severe asthma will be evaluated during and after a six week trial of triple therapy (ICS/LABA/LAMA) for changes in 129Xe MRI ventilation percent defect, pulmonary function measurements.

Drug: FF/UMEC/VI

Interventions

FF/UMEC/VI DRUG

The investigational drug is a single Ellipta inhaler containing 200 ug fluticasone furoate, 62.5 ug umedlidinium and 25 ug vilanterol. The drug is delivered in an Ellipta inhaler in a single dose once daily.

Also known as: Trelegy

Participants with poorly controlled moderate to severe asthma

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. Grace Parraga: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Robarts Research Institute; The University of Western Ontario; London Health Sciences Centre

London, Ontario, N6A 5B7, Canada

Location

Related Publications (14)

• Kerwin E, Pascoe S, Bailes Z, Nathan R, Bernstein D, Dahl R, von Maltzahn R, Robbins K, Fowler A, Lee L. A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids. Respir Res. 2020 Jun 12;21(1):148. doi: 10.1186/s12931-020-01400-5.

  PMID: 32532275 BACKGROUND

• Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention: Updated 2017. (2017).

  BACKGROUND

• Dreher M, Muller T. Add-on Therapy for Symptomatic Asthma despite Long-Acting Beta-Agonists/Inhaled Corticosteroid. Tuberc Respir Dis (Seoul). 2018 Jan;81(1):1-5. doi: 10.4046/trd.2017.0102. Epub 2017 Dec 13.

  PMID: 29256220 BACKGROUND

• Walford HH, Doherty TA. Diagnosis and management of eosinophilic asthma: a US perspective. J Asthma Allergy. 2014 Apr 11;7:53-65. doi: 10.2147/JAA.S39119. eCollection 2014.

  PMID: 24748808 BACKGROUND

• de Groot JC, Ten Brinke A, Bel EH. Management of the patient with eosinophilic asthma: a new era begins. ERJ Open Res. 2015 Sep 23;1(1):00024-2015. doi: 10.1183/23120541.00024-2015. eCollection 2015 May.

  PMID: 27730141 BACKGROUND

• Fain S, Schiebler ML, McCormack DG, Parraga G. Imaging of lung function using hyperpolarized helium-3 magnetic resonance imaging: Review of current and emerging translational methods and applications. J Magn Reson Imaging. 2010 Dec;32(6):1398-408. doi: 10.1002/jmri.22375.

  PMID: 21105144 BACKGROUND

• Altes TA, Powers PL, Knight-Scott J, Rakes G, Platts-Mills TA, de Lange EE, Alford BA, Mugler JP 3rd, Brookeman JR. Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings. J Magn Reson Imaging. 2001 Mar;13(3):378-84. doi: 10.1002/jmri.1054.

  PMID: 11241810 BACKGROUND

• Aysola R, de Lange EE, Castro M, Altes TA. Demonstration of the heterogeneous distribution of asthma in the lungs using CT and hyperpolarized helium-3 MRI. J Magn Reson Imaging. 2010 Dec;32(6):1379-87. doi: 10.1002/jmri.22388.

  PMID: 21105142 BACKGROUND

• Svenningsen S, Kirby M, Starr D, Coxson HO, Paterson NA, McCormack DG, Parraga G. What are ventilation defects in asthma? Thorax. 2014 Jan;69(1):63-71. doi: 10.1136/thoraxjnl-2013-203711. Epub 2013 Aug 16.

  PMID: 23956019 BACKGROUND

• Campana L, Kenyon J, Zhalehdoust-Sani S, Tzeng YS, Sun Y, Albert M, Lutchen KR. Probing airway conditions governing ventilation defects in asthma via hyperpolarized MRI image functional modeling. J Appl Physiol (1985). 2009 Apr;106(4):1293-300. doi: 10.1152/japplphysiol.91428.2008. Epub 2009 Feb 12.

  PMID: 19213937 BACKGROUND

• Costella S, Kirby M, Maksym GN, McCormack DG, Paterson NA, Parraga G. Regional pulmonary response to a methacholine challenge using hyperpolarized (3)He magnetic resonance imaging. Respirology. 2012 Nov;17(8):1237-46. doi: 10.1111/j.1440-1843.2012.02250.x.

  PMID: 22889229 BACKGROUND

• Kruger SJ, Niles DJ, Dardzinski B, Harman A, Jarjour NN, Ruddy M, Nagle SK, Francois CJ, Sorkness RL, Burton RM, Munoz del Rio A, Fain SB. Hyperpolarized Helium-3 MRI of exercise-induced bronchoconstriction during challenge and therapy. J Magn Reson Imaging. 2014 May;39(5):1230-7. doi: 10.1002/jmri.24272. Epub 2013 Sep 4.

  PMID: 24006239 BACKGROUND

• Samee S, Altes T, Powers P, de Lange EE, Knight-Scott J, Rakes G, Mugler JP 3rd, Ciambotti JM, Alford BA, Brookeman JR, Platts-Mills TA. Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: assessment of response to methacholine and exercise challenge. J Allergy Clin Immunol. 2003 Jun;111(6):1205-11. doi: 10.1067/mai.2003.1544.

  PMID: 12789218 BACKGROUND

• Tzeng YS, Lutchen K, Albert M. The difference in ventilation heterogeneity between asthmatic and healthy subjects quantified using hyperpolarized 3He MRI. J Appl Physiol (1985). 2009 Mar;106(3):813-22. doi: 10.1152/japplphysiol.01133.2007. Epub 2008 Nov 20.

  PMID: 19023025 BACKGROUND

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Dr. Grace E Parraga
• Organization: Western Universtiy

gparraga@robarts.ca

519-931-5365

Study Officials

• Grace E Parraga, PhD

  Robarts Research Institute, The University of Western Ontario

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: single arm, open-label pilot study

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: December 3, 2020
• Study Start: August 8, 2022
• Primary Completion: August 25, 2023
• Study Completion: December 1, 2025
• Last Updated: August 29, 2025
• Results First Posted: March 29, 2024

Record last verified: 2025-08

Locations

CA (1)