Efficacy and Safety of Benralizumab in Patients With Non-cystic Fibrosis Bronchiectasis

NCT05006573 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: D325BC000012020-004068-24
• Study Type: interventional
• Target: 100
• Locations: 16 countries
• Sites: 48

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).

Conditions

Non-cystic Fibrosis Bronchiectasis

Keywords

Benralizumab; Non-cystic Fibrosis Bronchiectasis; Eosinophlic Inflammation

Outcome Measures

Primary Outcomes (1)

• Annualized Bronchiectasis Exacerbations Rate in the Double-blind Period

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

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

Secondary Outcomes (12)

• 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

Study Arms (2)

Benralizumab

EXPERIMENTAL

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

Biological: Benralizumab

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo to Benralizumab

Interventions

Benralizumab BIOLOGICAL

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

Benralizumab

Placebo to Benralizumab BIOLOGICAL

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

Placebo

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (48)

Research Site

Birmingham, Alabama, 35233, United States

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Newport Beach, California, 92663, United States

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Northridge, California, 91324, United States

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El Paso, Texas, 79902, United States

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Florida, B1602DQD, Argentina

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San Fernando, B1646EBJ, Argentina

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San Miguel de Tucumán, 4000, Argentina

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Melbourne, 3004, Australia

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South Brisbane, 4101, Australia

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Ajax, Ontario, L1S 2J5, Canada

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Burlington, Ontario, L7N 3V2, Canada

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Windsor, Ontario, N8X-5A6, Canada

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Guangzhou, 510120, China

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Guangzhou, China

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Shanghai, 200032, China

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Zhengzhou, 450000, China

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Aalborg, 9000, Denmark

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Hellerup, 2900, Denmark

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Hvidovre, 2650, Denmark

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Vejle, 7100, Denmark

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Essen, 45239, Germany

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Frankfurt, 60590, Germany

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Gauting, 82131, Germany

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München, D-80336, Germany

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Coimbatore, 641028, India

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Hyderabad, 500084, India

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New Delhi, 100049, India

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Milan, 20122, Italy

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Pisa, 56100, Italy

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Roma, 00168, Italy

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Rozzano, 20089, Italy

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Quezon City, 1100, Philippines

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Bydgoszcz, 85-079, Poland

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Ostrowiec Świętokrzyski, 27-400, Poland

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Wroclaw, 54-239, Poland

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Penza, 440067, Russia

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Saratov, 410012, Russia

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Ulyanovsk, 432009, Russia

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Jeonju, 54907, South Korea

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Seoul, 04763, South Korea

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Seoul, 05030, South Korea

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Seoul, 06591, South Korea

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Barcelona, 08003, Spain

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Madrid, 28040, Spain

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Southampton, SO9 4XY, United Kingdom

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Hochiminh, 70000, Vietnam

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Related Links

• MAHALE Poster Master US
• CSR Synopsis

MeSH Terms

Interventions

benralizumab

Results Point of Contact

• Title: Global Clinical Head
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• James D. Chalmers, MD

  University of Dundee, Nethergate, Dundee DD1 4HN, Scotland, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: August 16, 2021
• Study Start: July 21, 2021
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: July 20, 2025
• Results First Posted: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (4); ES (2); PL (3); RU (3); GB (1); IN (3); CA (3); DK (4); AR (3); IT (4); DE (4); CN (4); VN (3); AU (2); KR (4); PH (1)