An exploratory study to assess the effect of benralizumab on small airway obstruction in patients with severe asthma using functional respiratory imaging

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

1. Patients eligible for treatment with benralizumab will be aged 18 - 75 years
and have a confirmed diagnosis of severe eosinophilic asthma according to
ERS/ATS guidelines.
2. Pre-bronchodilator FEV1 of * 80% predicted and history of
physician-diagnosed asthma requiring treatment with medium-to-high dose ICS
(>250µg fluticasone dry powder formulation equivalents total daily dose) and a
LABA, for at least 12 months prior to Visit 1.
3. All patients will show persistent blood eosinophilia of >0.3 x 10E9/L
despite treatment with high doses of inhaled corticosteroids (>500 ug/day
fluticasone equivalent), or >0.15 x 10E9/L despite chronic oral corticosteroid
treatment at baseline.
4. At least 2 documented asthma exacerbations in the 12 months prior to the
date informed consent.
5. Females of childbearing potential must have a negative pre-treatment urine
pregnancy test

Exclusion Criteria

1. Current smokers or former smokers with a smoking history of >=15 pack years.
A former smoker is defined as a subject who quit smoking at least 6 months
prior to Visit 1
2. Chronic pulmonary disorders other than asthma
3. Current malignancy or previous malignancy in remission <12 months
4. Prior use of anti IL5 or anti 5 R monoclonal Antibodies. For patients
treated with omalizumab there is a wash out period of 3 month.
5. Any other condition that, according to the investigator, may affect the
outcome of the study

Study & Design

Study Type: Observational non invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Absolute change in specific airway volume (siVaw) at FRC & TLC during treatment<br /><br>with benralizumab after 4 and 12 weeks · Absolute change in specific airway<br /><br>resistance (siRaw) at FRC & TLC during treatment with benralizumab after 4 and<br /><br>12 weeks.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Change in other FRI parameters (absolute change in values or percent<br /><br>predicted at baseline, after 4 and 12 weeks of treatment):<br /><br>• airway wall volume<br /><br>• air trapping<br /><br>• Internal Lobar Airflow Distribution<br /><br>• Image based lobe volumes<br /><br><br /><br>2. Change in spirometry parameters: FEV1, FVC,FEF 25-75, tiffeneau index<br /><br>(FEV1/FVC ratio), IC<br /><br>3. Change in body plethysmography parameters: RV, TLC, FRC, Raw, Sraw, Sgaw<br /><br>4. Change in FeNO (Fractional concentration of exhaled nitric oxide)<br /><br>5. Change in FOT (Forced oscillation technique= measurement of airway<br /><br>impedance)<br /><br>5. Change in Patient reported outcomes: ACQ, SGRQ<br /><br>6. Change in exercise tolerance: 6MWT<br /><br>7. Change in blood eosinophil count<br /><br><br /><br>All other parameters will be evaluated at baseline, after 1 week, 4 weeks and<br /><br>12 weeks of treatment, and correlated with changes in FRI parameters:</p><br>