Resumen

This is a multicentre, randomised, double-blind, parallel-group, placebo-controlled, phase III study originally designed to test the hypothesis that benralizumab will reduce exacerbation rates compared with placebo on top of standard-of-care therapy in adult patients with non-cystic fibrosis bronchiectasis with eosinophilic inflammation (NCFB+EI). All patients who complete the double-blind treatment period (28 to 52 weeks depending on the timing of patient randomization and when the revised CSP version 3.0 becomes effective) on investigational product (IP) may be eligible to continue into an open-label extension (OLE) period during which all patients will receive benralizumab. The revised OLE period is intended to allow patients approximately 32 weeks of treatment with open label benralizumab (24 weeks followed by a FU visit 8 weeks after the last dose of IP for a total of approximately 32 weeks).

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 130 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

Affect the safety of the patient during the study.
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:
Influence the findings of the study or their interpretation.
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:
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
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
Current smokers with a tobacco history of ≥ 10 pack-years or ex-smoker with a tobacco history of ≥ 10 pack-years.
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.

Intervenciones

biological

Benralizumab

Benralizumab active solution in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume

biological

Placebo to Benralizumab

Matching placebo solution in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume

A Multicentre, Randomised, Double-blind, Parallel-group, Placebo-controlled, 52 Week, Phase III Study With an Open-label Extension to Evaluate the Efficacy and Safety of Benralizumab in Patients With Non-Cystic Fibrosis Bronchiectasis (MAHALE)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Benralizumab

Placebo to Benralizumab

Ubicaciones

Research Site

Research Site

Research Site

Patrocinadores