|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Non-cystic fibrosis bronchiectasis (NCFB)
|Medical condition in easily understood language
|Non-cystic Fibrosis Bronchiectasis (NCFB)
|Diseases [C] - Respiratory Tract Diseases [C08]
|E.1.2 Medical condition or disease under investigation
|Non-cystic fibrosis bronchiectasis
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To evaluate the effect of benralizumab on bronchiectasisexacerbations - annualised exacerbation rate estimated forthe DB treatment period
|Secondary objectives of the trial
|To evaluate the effect of benralizumab on:
- time to onset of bronchiectasis exacerbations
- respiratory symptoms
- pulmonary function
- cough-related quality of life
- bronchiectasis health-related quality of life
- respiratory health status/health-related quality of life
To evaluate the safety and tolerability of benralizumab
|Trial contains a sub-study
|Principal inclusion criteria
|- Male or female, at least 18 years of age inclusive at the time of signing the ICF
- 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).
- Documented history of 2 or more bronchiectasis exacerbations within a year of the screening visit.
- 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
- Must be on airway clearance therapy, physiotherapy, or mucus clearance therapy.The dose and regimen of these therapies and any drugs used to aid expectoration should be stable for at least 3 months prior to the screening visit and remain stable throughout the DB period of the study.
- If receiving inhaled corticosteroid or bronchodilator 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.
- Women of childbearing potential (WOCBP) must have a negative serum and urine pregnancy test prior to randomization and agree to use a highly effective method of birth control from enrollment, throughout the study duration, and for 12 weeks after the last dose of IP.
|Principal exclusion criteria
|- Pulmonary disease other than bronchiectasis. 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.
- Another diagnosed or suspected pulmonary or systemic disease associated with elevated peripheral eosinophil counts
- Respiratory infection or bronchiectasis exacerbation during the screening period.
- Any other clinical condition 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.
- Radiological findings suggestive of a 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 > 6 mm in size should have at least 2 years of follow up with no change on CT imaging.
- Current active liver disease
- 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 cervix are eligible provided the patient is in remission and curative therapy was completed at least 12 months prior to Visit 1
b. Patients who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to Visit 1.
- History of known immunodeficiency disorder including a positive test for human immunodeficiency virus, HIV-1 or HIV-2.
- History of alcohol or drug abuse within the past year
- Patients receiving long-term oxygen treatment
- Patients participating in, or scheduled for, an intensive (active) pulmonary rehabilitation programme. Patients who are in the maintenance phase of a rehabilitation programme are eligible.
- Use of non-invasive positive-pressure ventilation for conditions other than obstructive sleep apnoea
- Use of immunosuppressive medication within 3 months of the screening visit or expected need for chronic use (≥ 4 weeks) during study
- Receipt of any marketed or investigational biologic products (monoclonal or polyclonal antibody) within one year of the screening visit
- Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to randomisation
- Receipt of immunoglobulin and blood products within 30 days of the date of the screening visit
- Receipt of live attenuated vaccines within 30 days of the date of randomisation
- Concurrent enrolment in another clinical drug interventional trial
- History of anaphylaxis to any biologic therapy or vaccine
- Known history of allergy or reaction to any component of the IP formulation.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements
- Previous randomisation in the present study
- Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
|E.5 End points
|Primary end point(s)
|Annualised exacerbation rate estimated for the DBtreatment period
|Timepoint(s) of evaluation of this end point
|over the DB treatment period (28 to 52 weeks)
|Secondary end point(s)
|- Time to first bronchiectasis exacerbation
- Change from baseline in Quality of Life-Bronchiectasis-Respiratory Symptoms (QoL-B-RSS)
- Change from baseline in pre-dose forced expiratoryvolume in 1 second (FEV1)
- Change from baseline in Leicester Cough Questionnaire(LCQ)
- Change from baseline in Quality of Life-Bronchiectasis(QoL-B) scales (excluding QoL-B-RSS key secondaryendpoint)
- Change from baseline in St. George's RespiratoryQuestionnaire (SGRQ)
- Safety and tolerability will be evaluated in terms of AEs,vital signs, clinical laboratory assessments, physicalexaminations, and ECGs
|Timepoint(s) of evaluation of this end point
|Over the DB treatment period
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The end of study is defined as the last expected visit/contact of the last patient undergoing the study.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days