Health Condition 1: J479- Bronchiectasis, uncomplicated
Conditions
Interventions
Intervention1: Benralizumab: Benralizumab, subcutaneous injection, every 4 weeks for 52 weeks
Control Intervention1: Placebo: Subcutaneous injection, every 4 weeks for 52 weeks
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Age Must be at least 18 years of age inclusive at the time of signing the ICF. Type of Participant and Disease Characteristics I. Must have NCFB diagnosed by a physician and confirmed by CT (measured at screening if a new CT is not possible, a CT performed within 12 months of the screening visit is acceptable). CT must demonstrate > 1 segment affected within a single lobe. On CT, small bronchiectasis features only visible in a single pulmonary segment and judged to be unrelated to clinical features will not be considered as meeting this criterion. II. Documented history of 2 or more bronchiectasis exacerbations within a year of the screening visit. NOTE: Examples of documentation include but not limited to: hospital records, medical records, prescription records, copies or transcriptions certified as being accurate copies (eg, X-rays, records kept at the pharmacy). I. At least 70% compliance on the daily BED ePRO assessment during the entire screening period. II. Greater than 50% compliance on the daily BED ePRO assessment in the 14-day period prior to the randomisation visit. III. If receiving prophylactic systemic or inhaled antibiotics to prevent bronchiectasis exacerbations, the dose/regimen must be stable for at least 3 months prior to the screening visit and remain stable throughout the DB period of the study. If prophylactic macrolides have been recently discontinued, patients must have been off treatment for at least 3 months prior to randomisation. In all other cases of prophylactic antibiotic use, >=4 weeks wash-out period should be in place after the last dose of antibiotic and prior to randomisation. IV. Patients must be on airway clearance therapy, physiotherapy, or mucus clearance therapy. Examples including active cycle of breathing techniques, postural drainage, positive expiratory pressure (eg, Acapella•), and other clearance devices. The dose and regimen of these therapies and any drugs used to aid expectoration (eg, hypertonic saline, isotonic saline, carbocysteine, N-acetylcysteine) should be stable for at least 3 months prior to the screening visit and remain stable throughout the DB period of the study. V. If receiving inhaled corticosteroid or bronchodilator (long-acting β-agonists and/or long-acting muscarinic antagonist) therapy, the dose and regimen should be stable with no alteration to dose or formulation for at least 3 months prior to the screening visit and this should remain stable throughout the DB period of the study. Sex Male or female Reproduction Negative pregnancy test (serum) for WOCBP at the screening visit WOCBP must: (a) Have a negative urine pregnancy test prior to randomisation, and (b) Must agree to use a highly effective method of birth control from enrolment, throughout the study duration, and for 12 weeks after the last dose of IP. Highly effective birth control methods (those that can achieve a failure rate of less than 1% per year when used consistently and correctly) include: a. Combined (Estrogen-and progestogen-containing) hormonal contraception associated with inhibition of ovulation -oral, intravaginal, or transdermal b. Progestogen-only hormonal contraception associated with inhibition of ovulation â??oral, injectable, or implantable c. Intrauterine device d. Intrauterine hormone-relea
Exclusion criteria
Exclusion criteria: Patients are excluded from the study if any of the following criteria apply: Medical Conditions I. Pulmonary disease other than bronchiectasis (eg, COPD, asthma, active lung infection including tuberculosis or NTM, pulmonary fibrosis, cystic fibrosis, primary ciliary dyskinesia, pulmonary hypertension, lung cancer, a1 anti-trypsin deficiency). Patients with a history of NTM disease may be enrolled if they have completed treatment prior to the screening visit, if at least 3 months have elapsed since the last day of antibiotic treatment for NTM at the screening visit, and if they have had a negative sputum culture prior to the screening visit. II. Another diagnosed or suspected pulmonary or systemic disease associated with elevated peripheral eosinophil counts (eg, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, allergic bronchopulmonary aspergillosis). III. Respiratory infection or bronchiectasis exacerbation during the screening period. In the event of a respiratory infection or bronchiectasis exacerbation during the screening period, the screening period may be extended once only after the last dose of antibiotics is given to ensure the patient has recovered from the infection or exacerbation. IV. A helminth parasitic infection diagnosed within 24 weeks of the screening visit that has not been treated with or has failed to respond to standard-of-care therapy. V. Any other clinical condition (ie, including but not limited to: cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment) that is not stable in the opinion of the Investigator and could: A. Affect the safety of the patient during the study. B. Influence the findings of the study or their interpretation. C. Impede the patient s ability to complete the entire duration of the study. VI. Radiological findings suggestive of a clinically important respiratory disease other than bronchiectasis, suggestive of acute infection, or of solitary pulmonary nodules without appropriate follow-up and demonstration of stability as per standard of care. Pulmonary nodules >6mm in size should have at least2 years of follow-up with no change on CT imaging. VII. Current active liver disease: A. Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen [HBsAg] or hepatitis C antibody) or other stable chronic liver disease is acceptable if patient otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. B. Patients with alanine aminotransferase or aspartate aminotransferase level >=3 times the upper limit of normal confirmed by repeated testing during screening period should not be randomised. Transient increase of aspartate aminotransferase/alanine aminotransferase level that resolves by the time of randomisation is acceptable if, in the Investigator s opinion, the patient does not have an active liver disease and meets other eligibility criteria. VIII. Current malignancy, or history of malignancy, except for: A. Patients who have had basal cell carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the effect of benralizumab 30 mg Q4W on bronchiectasis exacerbationsTimepoint: Annualized bronchiectasis exacerbation rate over the 52-week treatment period. i.e. Total number of bronchiectasis over a period of 52 weeks in Study arm and Placebo arm. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety Objective: To evaluate the safety and tolerability of benralizumab 30mg Q4W Timepoint: safety and tolerability will be evaluated in terms of AEs, vital signs, clinical laboratory assessments, physical examinations, and ECGs. Assessments related to AEs cover: I. Occurrence/Frequency II. Relationship to IP as assessed by Investigator III. Intensity IV. Seriousness V. Death VI. AEs leading to discontinuation of IP VII. Other significant AEs Will be assessed at baseline and 52 weeks ;To evaluate the effect of benralizumab 30 mg Q4W on bronchiectasis health-related quality of lifeTimepoint: Change from baseline in QoL-B scales (excluding QoL-B-RSS key secondary endpoint) over 52-week treatment period Will be assessed at baseline and 52 weeks;To evaluate the effect of benralizumab 30 mg Q4W on NCFB-related healthcare resource utilisationTimepoint: Frequency and annual rate of NCFB-related healthcare encounters (hospitalisation, ICU stay, emergency room visits, urgent care, specialist/GP visits, home healthcare), tests/procedures. Total hospital length of stay Will be assessed at baseline and 52 weeks;To evaluate the effect of benralizumab 30 mg Q4W on pulmonary functionTimepoint: Change from baseline in pre-dose FEV1over 52-weektreatment period Will be assessed at baseline and 52 weeks;To evaluate the effect of benralizumab 30 mg Q4W on respiratory health status/health-related quality of lifeTimepoint: Change from baseline in SGRQ over 52-week treatment period Will be assessed at baseline and 52 weeks;To evaluate the effect of benralizumab 30 mg Q4W on respiratory symptomsTimepoint: Change from baseline in QoL-B-RSS over 52-week treatment period Will be assessed at baseline and 52 weeks;To evaluate the effect of benralizumab 30 mg Q4W on severe bronchiectasis exacerbationsTimepoint: I. Annualised rate of severe bronchiectasis exacerbations at Week 52 II. Annualised rate of hospitalisations due to bronchiectasis exacerbations at Week 52 Will be | — |
Countries
Argentina, Australia, Canada, Chile, Denmark, Germany, India, Italy, Japan, Philippines, Poland, Republic of Korea, Russian Federation, Spain, United Kingdom, United States of America, Viet Nam
Contacts
Public ContactDr Santosh Kadam
AstraZeneca Pharma India Ltd
Outcome results
None listed