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

NCT03733535 | Active Not Recruiting

• 1 other identifier: ROB0042
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Asthma; Eosinophilic

Keywords

Benralizumab; Xenon

Outcome Measures

Primary Outcomes (1)

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

  Changes in VDP

  Day 0 and 28

Secondary Outcomes (14)

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

  Day 0, 14 and 112

• Change from baseline blood eosinophils

  Day 0, 14 and 112

• Change from baseline forced expiration volume in one second

  Day 0, 14, 28 and 112

• Change from baseline forced vital capacity

  Day 0, 14, 28 and 112

• Change from baseline lung volumes

  Day 0, 14, 28 and 112

Other Outcomes (12)

• Explore univariate correlation and linear regression of MRI ventilation defect percent and asthma control as measured by the Asthma Control Questionnaire

  Day 112

• Explore univariate correlation and linear regression of MRI ventilation defect percent and asthma-related quality of life as measured by the Asthma Quality of Life Questionnaire

  Day 112

• Explore univariate correlation and linear regression of MRI ventilation defect percent and daily life and perceived well-being as measured by the St. George's Respiratory Questionnaire

  Day 112

Study Arms (1)

Treatment

EXPERIMENTAL

Benralizumab 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.

Drug: Benralizumab; Drug: 129 Xenon

Interventions

Benralizumab DRUG

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

Also known as: Fasenra

Treatment

129 Xenon DRUG

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

Also known as: 129-Xe

Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Dr. Grace Parraga: lead
• AstraZeneca: collaborator

Study Sites (1)

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

London, Ontario, N6A 5B7, Canada

Location

Related Publications (2)

• 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.

  PMID: 36781102 DERIVED

• 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.

  PMID: 35283104 DERIVED

MeSH Terms

Conditions

Pulmonary Eosinophilia

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Grace E Parraga, PhD

  Robarts Research Institute, The University of Western Ontario

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Open-label, single arm

Study Record Dates

• First Submitted: November 2, 2018
• First Posted: November 7, 2018
• Study Start: March 1, 2022
• Primary Completion: March 20, 2022
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)