The Role of Benralizumab on airway Remodeling Assessed by HRCT in severe asthma (BREATH Study)

Phase 1

• Conditions: SEVERE ASTHMA; MedDRA version: 21.1Level: LLTClassification code 10068462Term: Eosinophilic asthmaSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2018-002498-23-IT
• Lead Sponsor: AZIENDA OSPEDALIERA UNIVERSITARIA POLICLINICO PAOLO GIACCONE” DI PALERMO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-24
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Male or female with age over 18 yrs.
2. Clinical diagnosis of persistent asthma for at least 6 months, according to GINA guidelines;
3. Existing treatment with high dose inhaled corticosteroids (ICS>500 mcg total daily dose of fluticasone propionate) in combination with other 2 controllers (LABA, LAMA, LTRA) for at least 3 months.
4. Positive methacholine challenge test (PC20 FEV1< 4mg/ml or PD20 FEV1<0.8 mg) or positive response to the spirometry with reversibility test in the previous year; reversibility test is positive if the pre-salbutamol FEV1 increases more than 200 mL and 12%, 15 min after the administration of 400 mg of salbutamol.
5. A forced expiratory volume in 1 second (FEV1<80% of predicted normal during the screening period);
6. History of 2 or more exacerbations in the previous year requiring systemic corticosteroids;
7. Blood eosinophil count of at least 300 cells per mcL.
8. Motivation to complete all the study visits and procedure, and ability to communicate well with the investigator and be capable of understanding the nature of the research.
9. Ability to comprehend and complete questionnaires on respiratory symptoms.
10. Written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

Exclusion Criteria

1. Inability to carry out pulmonary function testing;
2. Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary disease (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), cardiovascular diseases (cardiac arrhythmia, unstable angina, congestive heart failure, aneurysm), neurological or haematological autoimmune diseases;
3. Malignancy;
4. Any chronic diseases with prognosis < 2 years;
5. Pregnant or lactating females or not able to exclude pregnancy during the study period;
6. History of alcohol or drug abuse;
7. Current smoker with a smoking history >10 pack-years;
8. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study;
9. Patients who are participating to other clinical studies.
10. Impaired DLCO suggestive of diseases other than asthma (i.e. Emphysema).
11. A helminth parasitic infection within 24 weeks that has not been treated with, or has failed to respond to, standard of care therapy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: 1. to assess wthether the effect of Benralizumab on HRCT markers of remodeling parallels the improvement in the disease, assessed by a reduction in the frequency and severity of respiratory symptoms as well as rate and seveity of exacerbations.<br>2. to assess wthether the effect of Benralizumab on biomarkers of airways inflammation (exhaled bronchial and alveolar nitric oxide (NO) concentrations and blood and sputum eosinophils levels) parallels the improvement in the control of the disease, assessed by a reduction in the frequency and severity of respiratory symptoms as well as rate and seveity of exacerbations.;Main Objective: TO EVALUATE THE EFFICACY OF BENRALIZUMAB TO REDUCE AIRWAY INFLAMMATION AND FEATURE OF AIRWAY REMODELING EVALUATED BY HRCT;Primary end point(s): To reduce number of exacerbations and symptoms of severe asthma;Timepoint(s) of evaluation of this end point: 52 weeks