AzTrials
AzTrials

Asthma; EosinophilicAERFLONCT03733535

Evaluating the Effect of Benralizumab in Severe, Poorly-controlled Eosinophilic Asthma Using Inhaled Hyperpolarized 129-Xenon MRI

A study testing Benralizumab and 129 Xenon in people with Asthma; Eosinophilic, run by Dr. Grace Parraga at 1 site in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the effect of a drug called benralizumab in individuals with severe, poorly controlled asthma with eosinophilic airway inflammation. Eosinophils are a type of white blood cell that help fight off infections. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Asthma; Eosinophilic
What is being tested?
Benralizumab and 129 Xenon
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteCanada
Study dates
1 Mar 2022to Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient understands study procedures and is willing to participate in the study as indicated by the patient's signature
  • Provision of written, informed consent prior to any study specific procedures
  • Males and females with a clinical diagnosis of asthma aged 18 to 70 years, inclusively, at the time of Visit 1 (enrolment), under the care of a respirologist
  • Patient is a current non-smoker, having not smoked tobacco or cannabis 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-Provera (trademark) injections, oral contraceptive and Erva Patch (trademark) or Nuvaring (trademark)
  • 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 within 16 weeks after last dose of study drug, and have negative serum pregnancy test result on enrolment
Show all 14Show fewer
  • Male patients 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 16 weeks after last dose
  • Patient has documented treatment with medium- to high-dosage inhaled corticosteroids (ICS) (>250μg fluticasone dry powder formulation equivalents total daily dosage) and a long-acting β2-agonist (LABA) for at least 12 months prior to enrolment.
  • Patient has been treated with high dose ICS (at least 500μg/day fluticasone propionate dry powder formulation or equivalent daily) and LABA for at least 3 months prior to Visit 2 with or without oral corticosteroids (OCS) and additional asthma controllers
  • Patient demonstrates pre-bronchodilator (Pre-BD) forced expiratory volume in one second ˂ 80% predicted
  • Patient demonstrated significant bronchodilator reversibility (≥ 12% AND ≥ 200 mL improvement) or positive methacholine challenge test (PC20 < 4.0 mg/ml) in past 24 months
  • Patient has blood eosinophils ≥ 300 cells/μl
  • Patient has ACQ-6 ≥ 1.5 at visit 1
  • Patient has a history of poorly controlled asthma

Who cannot join

  • Patient is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand written material
  • Patient 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 patient throughout the study, influence the findings of the study or their interpretations, or impede the patient'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
  • History of anaphylaxis to any biologic therapy
  • A helminthic parasitic infection diagnosed within 24 weeks prior to the date of informed consent that has not been treated with or failed to respond to standard-of-care therapy
Show all 30Show fewer
  • Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date of informed consent
  • Use of immunosuppressive medication (including but not limited to methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid or any experimental anti-inflammatory therapy) within 3 months prior to the date of informed consent
  • Chronic maintenance prednisone for the treatment of asthma is allowed
  • Clinically significant asthma exacerbation, in the opinion of the investigator, including those requiring the use of OCS, or an increase in maintenance dosage of OCS 14 days prior to the date of informed consent
  • 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
  • Receipt of any marketed (e.g., omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date of informed consent, whichever is longer AND blood eosinophils ≥ 300 cells/µl.
  • Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to enrolment, whichever is longer
  • Previously randomized in any benralizumab (MEDI-563) study
  • Initiation of new allergen immunotherapy within 30 days prior to the date of informed consent
  • Current use of any oral of opthalmic nonselective β-adrenergic antagonist (e.g., propranolol)
  • Planned surgical procedure during the conduct of the study
  • Concurrent enrolment in another clinical trial
  • Patient has donated a unit of blood within 4 weeks prior to Visit 1 or anticipates donating blood at any time during the study
  • Patient has history of alcohol or drug abuse within 12 months prior to the date of informed consent
  • Patient is a female who is ≤8 weeks post-partum or breast feeding an infant
  • Patient is pregnant, or intends to become pregnant during the time course of the study
  • Patient is unable to perform MRI breath-hold maneuver
  • Patient is unable to perform spirometry maneuver
  • Patient 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
  • Patient has a blood pressure of >150 mmHg systolic or >95 mmHg diastolic on >2 measurements done >5 minutes apart at Visit 1 or Visit 2
  • Patient has ECG abnormalities consistent with previous myocardial infarction, hypertrophic cardiomyopathy, ischemic heart disease or conduction system disease
  • In the opinion of the investigator, patient suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia
  • Patient 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

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

    London, Ontario, N6A 5B7

Other trials in Canada

About this study

Official title: A Mechanistic Pilot Open-label Study to Evaluate the Effect of Benralizumab on Airway Function and Inflammation in Patients With Severe, Poorly-controlled Eosinophilic Asthma Using Inhaled Hyperpolarized 129-Xenon MRI

The purpose of this study is to evaluate the effect of a drug called benralizumab in individuals with severe, poorly controlled asthma with eosinophilic airway inflammation. Eosinophils are a type of white blood cell that help fight off infections. Some people with asthma have too many eosinophils in their airways and blood, which can cause airway inflammation. Benralizumab is a new drug that is Health Canada approved and has been shown to rapidly eliminate eosinophils. It has been used in patients with severe asthma to improve lung function and reduce flair-ups, also known as exacerbations. Magnetic Resonance Imaging (MRI) is an imaging tool that can look at the structure of the lungs when a subject inhales a xenon gas mixture. In healthy individuals, the gas fills the lungs evenly, but in individuals with lung disease, some of the areas of the lungs are not filled by the gas and the image looks patchy. These patchy areas are called ventilation defects and they contribute to reduced lung function. The goal of the study is to see if treatment with benralizumab will improve these ventilation defects, overall lung function and blood and sputum eosinophil levels. Subjects will receive treatment with benralizumab a total of 3 times, 4 weeks apart. Before and after treatment, subjects will undergo a series of MRI tests, breathing tests, blood and sputum analysis and a series of questionnaires to evaluate daily quality of life. The hypothesis is that ventilation defects will significantly improve after benralizumab treatment, and that this improvement will be different based on how long the patient has had asthma.

Read the detailed description

This is an open-label, single arm, pilot study in patients with severe, poorly-controlled eosinophilic asthma to quantify hyperpolarized 129-Xenon MRI ventilation defect percent (VDP) before and after benralizumab therapy administered every 4 weeks for the first three injections (subcutaneous injection). Male and female patients between 18 and 70 years of age will be screened (Enrolment, Visit 1) and those that satisfy all inclusion and exclusion criteria will undergo five additional two-hour study visits (Visit 2=Day 0/baseline, Visit 3=Day 14±2 days and Visit 4=Day 28±2 days, Visit 5=Day 56±2 days, Visit 6=112±2 days) which will involve spirometry, plethysmography for airways resistance (Raw) and lung volumes, forced oscillation technique (FOT), multiple breath nitrogen washout (MBNW) for the lung clearance index (LCI) and 129-Xenon MRI pre- and post-bronchodilator, with the exception of Visit 5, which will not include MRIs. At all visits fractional exhaled nitric oxide (FeNO) will be measured pre-bronchodilator. The Asthma Control Questionnaire (ACQ-6), the Asthma Quality of Life Questionnaire (AQLQ) and the St. George's Respiratory Questionnaire (SQRQ) will be completed at all visits except Visit 3. Sputum induction will be performed on Visits 2 and 4 to measure sputum eosinophils, and blood samples will be performed on Visits 1 and 4 to measure blood eosinophils. Participants that satisfy all inclusion and exclusion criteria will complete a total of six study visits. Upon study enrolment, all participants will be allocated to a benralizumab treatment arm (30 mg injection after completion of study assessments on Visit 2/Day 0, Visit 4/Day 28 and Visit 5/Day 56). After Visit 6/Day 112, all participants will be offered participation in the AstraZeneca Patient Support Program to receive benralizumab therapy on Day 112 and every 8 weeks thereafter.

Being tested
Benralizumab, 129 Xenon
Keywords
Benralizumab, Xenon
Medical subject headings
Pulmonary Eosinophilia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BenralizumabDrug

    Also called Fasenra

    Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody

  • 129 XenonDrug

    Also called 129-Xe

    1.0 L of 129-Xenon/4-Helium mixture to acquire MRI images

Study groups in NCT03733535
Study groupRoleWhat they receive
TreatmentExperimentalBenralizumab 30mg subcutaneous injection on study days 0, 28 and 56 and 1.0 L 129-Xenon/4-Helium mixture, twice per visit, on days 0, 14, 28 and 112.
Receives: Drug: Benralizumab; Drug: 129 Xenon

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline airway function measured using 129-Xenon MRI ventilation defect percent

    Changes in VDP

    Measured: Day 0 and 28

Secondary outcomes (14)

  1. Change from baseline airway function measured using 129-Xenon MRI ventilation defect percent

    Changes in VDP

    Measured: Day 0, 14 and 112

  2. Change from baseline blood eosinophils

    Measured: Day 0, 14 and 112

  3. Change from baseline forced expiration volume in one second

    Indicator of pulmonary function

    Measured: Day 0, 14, 28 and 112

  4. Change from baseline forced vital capacity

    Indicator of pulmonary function

    Measured: Day 0, 14, 28 and 112

  5. Change from baseline lung volumes

    Indicator of pulmonary function

    Measured: Day 0, 14, 28 and 112

  6. Change from baseline airways resistance

    Indicator of pulmonary function and inflammation

    Measured: Day 0, 14, 28 and 112

  7. Change from baseline forced oscillation technique

    Indicator of pulmonary function and inflammation

    Measured: Day 0, 14, 28 and 112

  8. Change from baseline lung clearance index

    Indicator of pulmonary function

    Measured: Day 0, 14, 28 and 112

  9. Change from baseline fraction exhaled nitric oxide

    Indicator of pulmonary function and inflammation

    Measured: Day 0, 14, 28 and 112

  10. Change from baseline in asthma control

    Asthma Control Questionnaire (ACQ-6) is used to evaluate asthma control. The ACQ-6 is scored from 0 to 6, with higher scores indicating more severely uncontrolled asthma.

    Measured: Day 0, 28, 56 and 112

  11. Change from baseline in asthma-related quality of life

    Asthma Quality of Life Questionnaire with Standardised Activities (AQLQ(S)) evaluates asthma-related quality of life. The AQLQ(S) is scored from 1-7, with lower scores indicating more severe impairment.

    Measured: Day 0, 28, 56 and 112

  12. Change from baseline in daily life and perceived well-being

    St. George's Respiratory Questionnaire (SGRQ) evaluates daily life and perceived well-being in relation to asthma and respiratory conditions. The SGRQ is scored from 0-100 with higher scores indicating more limitations.

    Measured: Day 0, 28, 56 and 112

  13. Change from baseline in Clinician Global Impressions of Change

    The Clinical Global Impressions of Change is an indicator of improvement or decline in clinical status from the perspective of the clinician. It is a scale from 1-7, with lower scores indicating more improvement in clinical status.

    Measured: Day 0 and 112

  14. Change from baseline in Patient Global Impressions of Change

    The Patient Global Impressions of Change is an indicator of improvement or decline in clinical status from the perspective of the patient. It is a scale from 1-7, with lower scores indicating more improvement in clinical status.

    Measured: Day 0 and 112

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2018
  2. Study start1 Mar 2022
  3. Primary completion20 Mar 2022
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open-label, single arm
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03733535
Sponsor's protocol ID
ROB0042
Acronym
AERFLO
Status last verified
Jul 2025
First submitted
2 Nov 2018
Last updated
11 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • McIntosh MJ, Kooner HK, Eddy RL, Wilson A, Serajeddini H, Bhalla A, Licskai C, Mackenzie CA, Yamashita C, Parraga G. CT Mucus Score and 129Xe MRI Ventilation Defects After 2.5 Years' Anti-IL-5Ralpha in Eosinophilic Asthma. Chest. 2023 Jul;164(1):27-38. doi: 10.1016/j.chest.2023.02.009. Epub 2023 Feb 11.

    PubMed 36781102

  • McIntosh MJ, Kooner HK, Eddy RL, Jeimy S, Licskai C, Mackenzie CA, Svenningsen S, Nair P, Yamashita C, Parraga G. Asthma Control, Airway Mucus, and 129Xe MRI Ventilation After a Single Benralizumab Dose. Chest. 2022 Sep;162(3):520-533. doi: 10.1016/j.chest.2022.03.003. Epub 2022 Mar 10.

    PubMed 35283104

Questions about this trial

What is this clinical trial studying?

A study testing Benralizumab and 129 Xenon in people with Asthma; Eosinophilic, run by Dr. Grace Parraga at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline airway function measured using 129-Xenon MRI ventilation defect percent (time frame: Day 0 and 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03733535, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in