Clinical trial NCT05552508: BURAN: Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging
Official title: BURAN: Effects of Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging Parameters
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: BURAN
Inhaled Corticosteroids
Long-acting β2 agonists
Benralizumab
Eosinophilic Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-09-23
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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 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).

Primary outcomes:
measure: Change From Baseline in Untrimmed Total Mucus Volume at TLC
timeFrame: Baseline and Week 13
Secondary outcomes:
measure: Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Air Trapping at FRC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Trimmed Distal Airway Wall Volume at TLC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Distal Airway Volume at TLC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Distal Airway Volume at Functional Residual Capacity (FRC)
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Lung Volume at TLC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Lung Volume at FRC
timeFrame: Baseline and Week 13
measure: Correlation Between Untrimmed Total Mucus Volume Measured at TLC and Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1)
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Mucus Plugs Score at TLC and Pre-BD FEV1
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Air Trapping at FRC and Pre-BD FEV1
timeFrame: At Baseline (Week 0)
measure: Correlation Between Trimmed Distal Airway Wall Volume at TLC and Pre-BD FEV1
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Distal Airway Volume at TLC and Pre-BD FEV1
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Distal Airway Volume at FRC and Pre-BD FEV1
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Lung Volume at TLC and Pre-BD FEV1
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Lung Volume at FRC and Pre-BD FEV1
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Mucus Volume Measured at TLC and Pre-bronchodilator Forced Vital Capacity (Pre-BD FVC)
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Mucus Plugs Score at TLC and Pre-BD FVC
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Air Trapping at FRC and Pre-BD FVC
timeFrame: At Baseline (Week 0)
measure: Correlation Between Trimmed Distal Airway Wall Volume at TLC and Pre-BD FVC
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Distal Airway Volume at TLC and Pre-BD FVC
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Distal Airway Volume at FRC and Pre-BD FVC
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Lung Volume at TLC and Pre-BD FVC
timeFrame: At Baseline (Week 0)
measure: Correlation Between Untrimmed Total Lung Volume at FRC and Pre-BD FVC
timeFrame: At Baseline (Week 0)
measure: Change From Baseline in Untrimmed Total Mucus Volume Measured at TLC With and Without Adjustment for Pre-BD FEV1
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC With and Without Adjustment for Pre-BD FEV1
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Air Trapping at FRC With and Without Adjustment for Pre-BD FEV1
timeFrame: Baseline and Week 13
measure: Change From Baseline in Trimmed Distal Airway Wall Volume at TLC With and Without Adjustment for Pre-BD FEV1
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FEV1
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FEV1
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Mucus Volume Measured at TLC With and Without Adjustment for Pre-BD FVC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC With and Without Adjustment for Pre-BD FVC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Air Trapping at FRC With and Without Adjustment for Pre-BD FVC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Trimmed Distal Airway Wall Volume at TLC With and Without Adjustment for Pre-BD FVC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FVC
timeFrame: Baseline and Week 13
measure: Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FVC
timeFrame: Baseline and Week 13
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From screening (Day -21) to follow-up (up to 1.9 years)
Other outcomes:
Locations:
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: Loxahatchee Groves
country: United States
facility: Research Site
state: Florida
city: Plantation
country: United States
facility: Research Site
state: Florida
city: Greenwood
country: United States
facility: Research Site
state: Indiana
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: DuBois
country: United States
facility: Research Site
state: Pennsylvania
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Webster
country: United States
facility: Research Site
state: Texas
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Clayton
country: Australia
facility: Research Site
city: Toorak Gardens
country: Australia
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Namur
country: Belgium
facility: Research Site
city: Montpellier Cedex 5
country: France
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Villarreal (Castellón)
country: Spain
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
References: