BURAN: Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging (BURAN)

BURAN: Effects of Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging Parameters

This study will assess the effects of benralizumab on airway dynamics in severe eosinophilic asthma in terms of quantitative computed tomography (CT)-derived measurements of pulmonary structure and function using the Functional Respiratory Imaging (FRI) platform.

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma
• Intervention / Treatment: Combination product: Benralizumab

Detailed Description

This is a phase IV, interventional single group, open-label, uncontrolled, prospective, multicenter clinical trial.

This study will be conducted in male and female participants ≥18 years old with established severe eosinophilic asthma as defined by European Respiratory Society (ERS)/American Thoracic Society (ATS) clinical guidelines inadequately controlled by treatment with Inhaled Corticosteroids-Long-acting β2 agonists (ICS-LABA) with or without oral corticosteroids (OCS) or other asthma controller medications.

Each participant will participate in the study for a minimum of 15 weeks and up to 23 weeks.

This study will comprise of:

Screening visit (V0) Visit 1 (V1; week 0; within 1 to 21 days of screening) Visit 2 (V2; week 4 ± 5 days) Visit 3 (V3; week 8 ± 5 days) Visit 4 (V4; week 13 ± 5 days) Follow-up (2 weeks [± 7 days] after V4) - Phone call follow-up. Participants will be discharged from the study after the phone call follow-up is completed.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Research Site
  • Frankston, Australia, 3199
    • Research Site
  • Toorak Gardens, Australia, 5065
    • Research Site
• Belgium
  • Liege, Belgium, 4000
    • Research Site
  • Mechelen, Belgium, 2800
    • Research Site
  • Montigny-le-Tilleul, Belgium, 6110
    • Research Site
  • Namur, Belgium, 5101
    • Research Site
  • Roeselare, Belgium, 8800
    • Research Site
• France
  • Cannes, France, 06414
    • Research Site
  • Clermont-Ferrand, France, 63003
    • Research Site
  • Libourne Cedex, France, 33505
    • Research Site
  • Montpellier Cedex 5, France, 34295
    • Research Site
• Portugal
  • Lisboa, Portugal, 1649-035
    • Research Site
  • Porto, Portugal, 4100-180
    • Research Site
• Spain
  • Alzira, Spain, 46410
    • Research Site
  • Barcelona, Spain, 08006
    • Research Site
  • Barcelona, Spain, 8003
    • Research Site
  • Barcelona, Spain, 08017
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Santander, Spain, 39008
    • Research Site
  • Villarreal (Castellón), Spain, 12540
    • Research Site
• United Kingdom
  • Bradford, United Kingdom, BND9 6RJ
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
• United States
  • California
    • Walnut Creek, California, United States, 94598
      • Research Site
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Research Site
    • Plantation, Florida, United States, 33324
      • Research Site
  • Indiana
    • Greenwood, Indiana, United States, 46143
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Research Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Research Site
  • Texas
    • Tyler, Texas, United States, 75708
      • Research Site
    • Webster, Texas, United States, 77598
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who are diagnosed with asthma with documented reversibility post-bronchodilator or salbutamol either historical or at Visit 0 (V0).
• Participants who have documented treatment with ICS and LABA for ≥ 3 months prior to V0 with or without oral corticosteroids and additional asthma controllers.
• Participants who have documented peripheral blood eosinophil count ≥ 300 cells/μL at V0, or if Oral Corticosteroids (OCS)-dependent, a documented peripheral blood eosinophil count ≥ 150 cells/μL at V0.
• Participants who have had a minimum of 2 exacerbations in the last 12 months prior to V0.
• Participants who have pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ≤ 70% at Visit 0 (V0).
• Participants who have pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) < 80% of predicted at V0.
• Participants who can perform acceptable and repeatable spirometry.
• Participants who can withhold asthma maintenance medication for at least 12 hours prior to V0, 1 and 4 where spirometry and/or Computed Tomography (CT) scan procedures will be performed except for once-a-day dosage where 24 hours will be required.
• Female participants who have a negative pregnancy test prior to administration of the investigational product (IP) and high-resolution CT scan and must agree to use a highly effective method of birth control from randomization throughout the study duration and within 12 weeks after last dose of IP.

Exclusion Criteria:

• Participants who are unstable or who experienced an exacerbation/infection in the 6 weeks before V0.
• Participants with acute upper or lower airway infection in the 6 weeks before V0.
• Participants diagnosed with clinically important pulmonary disease other than asthma, or participants who have ever been diagnosed with pulmonary or systemic disease, other than asthma that are associated with elevated peripheral eosinophil count.
• Receipt of any biologic products for asthma within 4 months or 5 half-lives prior to V0 whichever is longer.
• History or current use of chronic (i.e., > 4 weeks) immunosuppressive medication.
• History of lung volume reduction surgery, lung resection, thermal bronchoplasty at any time before visit 0 (V0) or on active phase of pulmonary rehabilitation.
• Participants with current malignancy or history of malignancy.
• History of other clinically significant disease or abnormality.
• Participants with positive Hepatitis B, C or HIV.
• Participants with:

Positive COVID-19 test at V0, COVID-19 disease within 6 weeks before V0 or History of severe COVID-19 disease at any time, defined by the need for Intensive Care Unit stay or Mechanical Ventilation (invasive or non-invasive).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Benralizumab; Participants will receive 3 doses of benralizumab having a strength of 30 mg subcutaneously once every 4 weeks (Week 0, Week 4, and Week 8).	Combination product: Benralizumab; Participants will receive benralizumab subcutaneously.; Other Names: Fasenra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Total Mucus Volume	The change from baseline to Week 13 in total mucus volume of untrimmed airways measured using quantitative CT analysis following treatment with benralizumab calculated as the mean percent change from baseline will be assessed.	Baseline (at week 0), Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Total mucus plugs score	The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by mucus plugs scores will be assessed. High baseline mucus scores have shown to have significant improvements in Ventilation Defect Percent (VDP) and asthma control post-benralizumab while those with low mucus scores have not. The scale has an upper bound of 20. An increase in Mucus Plug Score implies an increase in the number of observed obstructive mucus plugs and is understood to represent a worse outcome. A decrease represents a decrease in the number of observed obstructive mucus plugs and is understood to represent a better outcome. Mucus plugs will be scored with a scoring system based on bronchopulmonary segmental anatomy. Each bronchopulmonary segment will be given a score of 1 (mucus plug present) or 0 (mucus plug absent).	Baseline (at week 0), Week 13
Change from baseline in Total air trapping	The change from baseline to Week 13 in total air trapping at functional residual capacity (FRC) measured using quantitative CT analysis following treatment with benralizumab will be assessed.	Baseline (at week 0), Week 13
Change from baseline in trimmed distal Airway wall volume (iVaww) at TLC	The change from baseline to Week 13 in trimmed distal iVaww at TLC measured using quantitative CT analysis following treatment with benralizumab will be assessed.	Baseline (at week 0), Week 13
Change from baseline in distal Specific airway volume (siVaw) at TLC	The change from baseline to Week 13 in trimmed distal siVaw at TLC measured using quantitative CT analysis following treatment with benralizumab will be assessed.	Baseline (at week 0), Week 13
Change from baseline in distal Specific airway volume (siVaw) at FRC	The change from baseline to Week 13 in trimmed distal siVaw at FRC measured using quantitative CT analysis following treatment with benralizumab will be assessed.	Baseline (at week 0), Week 13
Change from baseline in Total Lung volume (iVlung) at TLC	The change from baseline to Week 13 in total iVlung at TLC measured using quantitative CT analysis following treatment with benralizumab will be assessed.	Baseline (at week 0), Week 13
Change from baseline in Total Lung volume (iVlung) at FRC	The change from baseline to Week 13 in total iVlung at FRC measured using quantitative CT analysis following treatment with benralizumab will be assessed.	Baseline (at week 0), Week 13
Correlation between imaging endpoints (Primary and Secondary FRI endpoints) and pre-bronchodilator forced expiratory volume (pre-BD FEV1)	The relationship between imaging endpoints (total mucus volume at TLC, mucus plugs score at TLC, total air trapping at FRC, trimmed distal iVaww at TLC, trimmed distal siVaw at TLC and FRC, total iVlung at TLC and FRC and total mucus plugs score at TLC) and pre-BD FEV1 will be assessed.	Baseline (at week 0)
Correlation between imaging endpoints (Primary and Secondary FRI endpoints) and pre-bronchodilator forced vital capacity (pre-BD FVC)	The relationship between imaging endpoints (total mucus volume at TLC, total air trapping at FRC, trimmed distal iVaww at TLC, trimmed distal siVaw at TLC and FRC, total iVlung at TLC and FRC and total mucus plugs score at TLC) and pre-BD FVC will be assessed.	Baseline (at week 0)
Correlation between the change in imaging endpoints (Primary and Secondary FRI endpoints) and the change in pre-BD FEV1 (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FEV1	The relationship between change from baseline to Week 13 in imaging endpoints (total mucus volume at TLC, total air trapping at FRC, trimmed distal iVaww at TLC, trimmed distal siVaw at TLC and FRC, total iVlung at TLC and FRC and total mucus plugs score at TLC) and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Correlation between the change in imaging endpoints (Primary and Secondary FRI endpoints) and the change in pre-BD FVC (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FVC	The relationship between change from baseline to Week 13 in imaging endpoints (total mucus volume at TLC, total air trapping at FRC, trimmed distal iVaww at TLC, trimmed distal siVaw at TLC and FRC, total iVlung at TLC and FRC and total mucus plugs score at TLC) and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Number of patients with Adverse Events (AEs)	The safety and tolerability of benralizumab will be assessed.	From screening to follow-up (up to 1.9 years)
Change from baseline in Total Mucus Volume at TLC with and without adjustment for pre-BD FEV1	The relationship between change from baseline to Week 13 in total mucus volume at TLC measured using quantitative CT analysis and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Change from baseline in Total Mucus Volume at TLC with and without adjustment for pre-BD FVC	The relationship between change from baseline to Week 13 in total mucus volume at TLC measured using quantitative CT analysis and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Change from baseline in total air trapping with and without adjustment for pre-BD FEV1	The relationship between change from baseline to Week 13 in total air trapping at FRC measured using quantitative CT analysis and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Change from baseline in total air trapping with and without adjustment for pre-BD FVC	The relationship between change from baseline to Week 13 in total air trapping at FRC measured using quantitative CT analysis and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Change from baseline in trimmed distal iVaww at TLC with and without adjustment for pre-BD FEV1	The relationship between change from baseline to Week 13 in trimmed distal iVaww at TLC measured using quantitative CT analysis and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Change from baseline in trimmed distal iVaww at TLC with and without adjustment for pre-BD FVC	The relationship between change from baseline to Week 13 in trimmed distal iVaww at TLC measured using quantitative CT analysis and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Change from baseline in trimmed distal siVaw at TLC with and without adjustment for pre-BD FEV1	The relationship between change from baseline to Week 13 in trimmed distal siVaw at TLC measured using quantitative CT analysis and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Change from baseline in trimmed distal siVaw at TLC with and without adjustment for pre-BD FVC	The relationship between change from baseline to Week 13 in trimmed distal siVaw at TLC measured using quantitative CT analysis and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Change from baseline in trimmed distal siVaw at FRC with and without adjustment for pre-BD FEV1	The relationship between change from baseline to Week 13 in trimmed distal siVaw at FRC measured using quantitative CT analysis and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Change from baseline in trimmed distal siVaw at FRC with and without adjustment for pre-BD FVC	The relationship between change from baseline to Week 13 in trimmed distal siVaw at FRC measured using quantitative CT analysis and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Change from baseline in total iVlung at TLC with and without adjustment for pre-BD FEV1	The relationship between change from baseline to Week 13 in total iVlung at TLC measured using quantitative CT analysis and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Change from baseline in total iVlung at TLC with and without adjustment for pre-BD FVC	The relationship between change from baseline to Week 13 in total iVlung at TLC measured using quantitative CT analysis and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Change from baseline in total iVlung at FRC with and without adjustment for pre-BD FEV1	The relationship between change from baseline to Week 13 in total iVlung at FRC measured using quantitative CT analysis and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Change from baseline in total iVlung at FRC with and without adjustment for pre-BD FVC	The relationship between change from baseline to Week 13 in total iVlung at FRC measured using quantitative CT analysis and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Change from baseline in total mucus plugs score with and without adjustment for pre-BD FEV1	The relationship between change from baseline to Week 13 in total mucus plugs score measured using quantitative CT analysis and pre-BD FEV1 will be assessed.	Baseline (at week 0), Week 13
Change from baseline in total mucus plugs score with and without adjustment for pre-BD FVC	The relationship between change from baseline to Week 13 in total mucus plugs score measured using quantitative CT analysis and pre-BD FVC will be assessed.	Baseline (at week 0), Week 13
Change from baseline in imaging endpoints ( Primary and Secondary FRI endpoints) for every one percent correlation between pre-BD FEV1 and pre-BD FVC	The change from baseline to Week 13 in the estimated average change in each imaging endpoint (total mucus volume at TLC, total air trapping at FRC, trimmed distal iVaww at TLC, trimmed distal siVaw at TLC and FRC, total iVlung at TLC and FRC and total mucus plugs score at TLC) and pre-BD FEV1) for every one percent increase in pre-BD FEV1 and pre-BD FVC will be assessed.	Week 0, and Week 13

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2022
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Benralizumab; Eosinophilic Asthma; BURAN; Inhaled Corticosteroids; Long-acting β2 agonists
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Leukocyte Disorders; Eosinophilia; Hypereosinophilic Syndrome; Asthma; Pulmonary Eosinophilia; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: D3250R00107; 2022-000152-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No