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)

AstraZeneca1 site in 1 country100 target enrollmentJuly 21, 2021

ConditionsNon-cystic Fibrosis Bronchiectasis

InterventionsBenralizumab Placebo to Benralizumab

DrugsBenralizumab Placebo to Benralizumab

Overview

Phase: Phase 3
Intervention: Benralizumab
Conditions: Non-cystic Fibrosis Bronchiectasis
Sponsor: AstraZeneca
Enrollment: 100
Locations: 1
Primary Endpoint: Annualized Bronchiectasis Exacerbations Rate in the Double-blind Period
Status: Terminated
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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).

Registry

clinicaltrials.gov

Start Date

July 21, 2021

End Date

April 16, 2024

Last Updated

9 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

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.

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:
•Affect the safety of the patient during the study.
•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:

Arms & Interventions

Benralizumab

Benralizumab will be administered subcutaneously (SC) using an accessorized prefilled syringe (APFS)

Intervention: Benralizumab

Placebo

Matching placebo solution will be administered subcutaneously (SC) using an accessorized prefilled syringe (APFS)

Intervention: Placebo to Benralizumab

Outcomes

Primary Outcomes

Annualized Bronchiectasis Exacerbations Rate in the Double-blind Period

Time Frame: through Double-blind period, at least 28 weeks and up to 52 weeks

Annualized Non-Cystic Fibrosis Bronchiectasis (NCFB) exacerbations rate through end of double-blind treatment period.

Secondary Outcomes

Time to First Exacerbation in the Double-blind Treatment Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in QoL-B-RSS Over the Double-blind Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in Pre-dose Pre-BD FEV1 Over the Double-blind Treatment Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in LCQ Total Score Over the Double-blind Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Physical Functioning Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Role Functioning Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Emotional Functioning Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Social Functioning Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Vitality Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Health Perceptions Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Treatment Burden Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
Change From Baseline in SGRQ Total Score Over the Double-blind Treatment Period(through Double-blind period, at least 28 weeks and up to 52 weeks)