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

Asthma Clinical Trial

— BURAN  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05552508
• Other study ID #: D3250R00107
• Secondary ID: 2022-000152-11
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 11, 2022
• Est. completion date: July 31, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 44
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Asthma
• Pulmonary Eosinophilia

Intervention

Combination Product:
• Benralizumab
Participants will receive benralizumab subcutaneously.

Locations

Country	Name	City	State
Australia	Research Site	Clayton
Australia	Research Site	Frankston
Australia	Research Site	Toorak Gardens
Belgium	Research Site	Liege
Belgium	Research Site	Mechelen
Belgium	Research Site	Montigny-le-Tilleul
Belgium	Research Site	Namur
Belgium	Research Site	Roeselare
France	Research Site	Cannes
France	Research Site	Clermont-Ferrand
France	Research Site	Libourne Cedex
France	Research Site	Montpellier Cedex 5
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Spain	Research Site	Alzira
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Santander
Spain	Research Site	Villarreal (Castellón)
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Nottingham
United States	Research Site	Charlottesville	Virginia
United States	Research Site	DuBois	Pennsylvania
United States	Research Site	Greenwood	Indiana
United States	Research Site	Lexington	Kentucky
United States	Research Site	Loxahatchee Groves	Florida
United States	Research Site	Plantation	Florida
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Springfield	Massachusetts
United States	Research Site	Tyler	Texas
United States	Research Site	Walnut Creek	California
United States	Research Site	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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