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

• ClinicalTrials.gov Identifier: NCT05552508
• Recruitment Status: Recruiting
• First Posted: September 23, 2022
• Last Update Posted: March 16, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Combination Product: Benralizumab	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 138 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BURAN: Effects of Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging Parameters
• Actual Study Start Date: November 9, 2022
• Estimated Primary Completion Date: September 29, 2023
• Estimated Study Completion Date: November 10, 2023

Arms and Interventions

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 Name: Fasenra

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in specific airway volume (siVaw) [ Time Frame: Baseline (at week 0), Week 13 ]
   The change from baseline to Week 13 in siVaw of trimmed airways measured using quantitative CT analysis following treatment with benralizumab calculated as the mean percent change from baseline will be assessed.

Secondary Outcome Measures :

1. Change from baseline in Lung volume (iVlung) [ Time Frame: Baseline (at week 0), Week 13 ]
   The change from baseline to Week 13 in iVlung measured using quantitative CT analysis following treatment with benralizumab will be assessed.
2. Change from baseline in Lobar volume (iVlobe) [ Time Frame: Baseline (at week 0), Week 13 ]
   The change from baseline to Week 13 in iVlobe measured using quantitative CT analysis following treatment with benralizumab will be assessed.
3. Change from baseline in Airway volume (iVaww) [ Time Frame: Baseline (at week 0), Week 13 ]
   The change from baseline to Week 13 in iVaw measured using quantitative CT analysis following treatment with benralizumab will be assessed.
4. Change from baseline in air trapping [ Time Frame: Baseline (at week 0), Week 13 ]
   The change from baseline to Week 13 in air trapping measured using quantitative CT analysis following treatment with benralizumab will be assessed.
5. Change from baseline in Airway resistance (iRaw) [ Time Frame: Baseline (at week 0), Week 13 ]
   The change from baseline to Week 13 in airway resistance measured using quantitative CT analysis following treatment with benralizumab will be assessed.
6. Change from baseline in mucus plugs score [ Time Frame: Baseline (at week 0), Week 13 ]

   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).

7. Change from baseline in Blood Vessel measurements (BVX) measured in millilitres (mL) [ Time Frame: Baseline (at week 0), Week 13 ]

   BV5 - The change from baseline to Week 13 of BV5, the volume in milliliters of intrapulmonary vessel-like markings >= 5 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed.

   BV5-10 - The change from baseline to Week 13 of BV5-10, the volume in milliliters of intrapulmonary vessel-like markings >5 mm2 and < 10 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed.

   BV10 - The change from baseline to Week 13 of BV10, the volume in milliliters of intrapulmonary vessel-like markings >=10 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed

   TBV - The change from baseline to Week 13 of TBV, the volume in milliliters of all intrapulmonary vessel-like markings as measured by quantitative CT analysis will be assessed.

8. Percent change from baseline in BVX [ Time Frame: Baseline (at week 0), Week 13 ]

   BV5/TBV - The change from baseline to Week 13 of BV5/TBV, BV5 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV5/TBV)x100 will be assessed.

   BV5-10/TBV - The change from baseline to Week 13 of BV5-10/TBV, BV5-10 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV5-10/TBV)x100 will be assessed.

   BV10/TBV - The change from baseline to Week 13 of BV10/TBV, BV10 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV10/TBV)x100 will be assessed.

9. Change from baseline in Internal Airflow Distribution (IAD) [ Time Frame: Baseline (at week 0), Week 13 ]
   The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by IAD will be assessed.
10. Change from baseline in CT-based imaging ventilation heterogeneity, defined as the standard deviation of the histogram of voxel-wise deformation representing the local expansion of lung tissue during inspiration, measured by quantitative CT analysis [ Time Frame: Baseline (at week 0), Week 13 ]
    The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by ventilation mapping will be assessed.
11. Change from baseline in ventilation/perfusion mapping [ Time Frame: Baseline (at week 0), Week 13 ]
    The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by ventilation/perfusion mapping will be assessed. Ventilation/perfusion is an arithmetic manipulation of other outcome measures which results in a unitless number, and is arrived at for a given lobe by dividing the difference in lobar volume (iVlobe) between inspiratory (TLC) and expiratory (FRC) scans by the TBV for that lobe.
12. Correlation between imaging endpoints (FRI endpoints and mucus plugs score) and pre-bronchodilator forced expiratory volume (pre-BD FEV1) [ Time Frame: Baseline (at week 0) ]
    The relationship between imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FEV1 will be assessed.
13. Correlation between imaging endpoints (FRI endpoints and mucus plugs score) and pre-bronchodilator forced vital capacity (pre-BD FVC) [ Time Frame: Baseline (at week 0) ]
    The relationship between imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FVC will be assessed.
14. Correlation between the change in imaging endpoints (FRI endpoints and mucus plugs score) and the change in pre-BD FEV1 (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FEV1 will be assessed.
15. Correlation between the change in imaging endpoints (FRI endpoints and mucus plugs score) and the change in pre-BD FVC (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FVC will be assessed.
16. Number of patients with Adverse Events (AEs) [ Time Frame: From screening to follow-up (up to 1.4 years) ]
    The safety and tolerability of benralizumab will be assessed.
17. Change from baseline in siVaw with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in siVaw measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
18. Change from baseline in siVaw with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in siVaw measured using quantitative CT analysis and pre-BD FVC will be assessed.
19. Change from baseline in iVlung with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in iVlung measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
20. Change from baseline in iVlung with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in iVlung measured using quantitative CT analysis and pre-BD FVC will be assessed.
21. Change from baseline in iVlobe with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in iVlobe measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
22. Change from baseline in iVlobe with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in iVlobe measured using quantitative CT analysis and pre-BD FVC will be assessed.
23. Change from baseline in iVaww with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in iVaww measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
24. Change from baseline in iVaww with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in iVaww measured using quantitative CT analysis and pre-BD FVC will be assessed.
25. Change from baseline in air trapping with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in air trapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
26. Change from baseline in air trapping with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in air trapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
27. Change from baseline in iRaw with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in iRaw measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
28. Change from baseline in iRaw with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in iRaw measured using quantitative CT analysis and pre-BD FVC will be assessed.
29. Change from baseline in BVX with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in BVX measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
30. Change from baseline in BVX with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in BVX measured using quantitative CT analysis and pre-BD FVC will be assessed.
31. Change from baseline in IAD with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in IAD measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
32. Change from baseline in IAD with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in IAD measured using quantitative CT analysis and pre-BD FVC will be assessed.
33. Change from baseline in ventilation mapping with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in ventilation mapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
34. Change from baseline in ventilation mapping with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in ventilation mapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
35. Change from baseline in ventilation/perfusion mapping with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in ventilation/perfusion mapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
36. Change from baseline in ventilation/perfusion mapping with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in ventilation/perfusion mapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
37. Change from baseline in mucus plugs score with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in mucus plugs score measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
38. Change from baseline in mucus plugs score with and without adjustment for pre-BD FVC [ Time Frame: Baseline (at week 0), Week 13 ]
    The relationship between change from baseline to Week 13 in mucus plugs score measured using quantitative CT analysis and pre-BD FVC will be assessed.
39. Change from baseline in imaging endpoints (FRI endpoints and mucus plugs score) for every one percent correlation between pre-BD FEV1 and pre-BD FVC [ Time Frame: Week 0, and Week 13 ]
    The change from baseline to Week 13 in the estimated average change in each imaging endpoint (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) for every one percent increase in pre-BD FEV1 and pre-BD FVC will be assessed.

Eligibility Criteria

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

Criteria

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 Vital Capacity (FVC) < 65% of predicted at V0.
• Participants who have pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) < 80% of predicted at V0.
• Participants who have stable asthma regimen apart from the use of rescue medication including the use of any other asthma medication for at least 3 months prior to 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).

Contacts and Locations

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

Locations

United States, California

Research Site; Recruiting

Walnut Creek, California, United States, 94598

United States, Colorado

Research Site; Not yet recruiting

Denver, Colorado, United States, 80206

United States, Florida

Research Site; Recruiting

Loxahatchee Groves, Florida, United States, 33470

Research Site; Recruiting

Plantation, Florida, United States, 33324

United States, Indiana

Research Site; Recruiting

Greenwood, Indiana, United States, 46143

United States, Kentucky

Research Site; Recruiting

Lexington, Kentucky, United States, 40502

Research Site; Recruiting

Lexington, Kentucky, United States, 40536

United States, Massachusetts

Research Site; Not yet recruiting

Springfield, Massachusetts, United States, 01199

United States, Missouri

Research Site; Recruiting

Saint Louis, Missouri, United States, 63110

Research Site; Not yet recruiting

Saint Louis, Missouri, United States, 63110

United States, Pennsylvania

Research Site; Recruiting

DuBois, Pennsylvania, United States, 15801

United States, Tennessee

Research Site; Recruiting

Knoxville, Tennessee, United States, 37909

United States, Texas

Research Site; Recruiting

Tyler, Texas, United States, 75708

Research Site; Recruiting

Webster, Texas, United States, 77598

United States, Virginia

Research Site; Not yet recruiting

Charlottesville, Virginia, United States, 22908

Australia

Research Site; Not yet recruiting

Box Hill, Australia, 3128

Research Site; Not yet recruiting

Clayton, Australia, 3168

Research Site; Not yet recruiting

Frankston, Australia, 3199

Research Site; Not yet recruiting

Toorak Gardens, Australia, 5065

Belgium

Research Site; Not yet recruiting

Liege, Belgium, 4000

Research Site; Recruiting

Mechelen, Belgium, 2800

Research Site; Not yet recruiting

Montigny-le-Tilleul, Belgium, 6110

Research Site; Recruiting

Namur, Belgium, 5101

Research Site; Recruiting

Roeselare, Belgium, 8800

France

Research Site; Not yet recruiting

Bordeaux, France, 33076

Research Site; Not yet recruiting

Caen, France, F-14033

Research Site; Not yet recruiting

Cannes, France, 06414

Research Site; Not yet recruiting

Clermond Ferrand, France, 63003

Research Site; Not yet recruiting

Libourne Cedex, France, 33505

Research Site; Not yet recruiting

Montpellier Cedex 5, France, 34295

Portugal

Research Site; Not yet recruiting

Lisboa, Portugal, 1349-019

Research Site; Not yet recruiting

Lisboa, Portugal, 1649-035

Research Site; Not yet recruiting

Porto, Portugal, 4100-180

Spain

Research Site; Recruiting

Alzira, Spain, 46410

Research Site; Recruiting

Barcelona, Spain, 08006

Research Site; Recruiting

Barcelona, Spain, 8003

Research Site; Recruiting

Madrid, Spain, 28007

Research Site; Recruiting

Santander, Spain, 39008

Research Site; Recruiting

Villarreal (Castellón), Spain, 12540

United Kingdom

Research Site; Not yet recruiting

Bradford, United Kingdom, BND9 6RJ

Research Site; Recruiting

Nottingham, United Kingdom, NG5 1PB

Research Site; Not yet recruiting

St Just, United Kingdom, TR19 7HX

Sponsors and Collaborators

AstraZeneca

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05552508
• Other Study ID Numbers: D3250R00107; 2022-000152-11 ( EudraCT Number )
• First Posted: September 23, 2022
• Last Update Posted: March 16, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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.

• Supporting Materials: Study Protocol
• 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.
• 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.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:

BURAN; Inhaled Corticosteroids; Long-acting β2 agonists; Benralizumab; Eosinophilic Asthma

Additional relevant MeSH terms:

Asthma; Pulmonary Eosinophilia; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Benralizumab; Anti-Asthmatic Agents; Respiratory System Agents