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

Non-cystic Fibrosis Bronchiectasis Clinical Trial

— MAHALE  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05006573
• Other study ID #: D325BC00001
• Secondary ID: 2020-004068-24
• Status: Completed
• Phase: Phase 3
• Start date: July 21, 2021
• Est. completion date: April 16, 2024

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: April 16, 2024
• Est. primary completion date: April 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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:

1. Affect the safety of the patient during the study.

2. Influence the findings of the study or their interpretation.

3. 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:

1. 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

2. 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.

Related Conditions & MeSH terms

• Bronchiectasis
• Fibrosis
• Non-cystic Fibrosis Bronchiectasis

Intervention

Biological:
• Benralizumab
Benralizumab active solution in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume
• Placebo to Benralizumab
Matching placebo solution in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume

Locations

Country	Name	City	State
Argentina	Research Site	Florida
Argentina	Research Site	San Fernando
Argentina	Research Site	San Miguel de Tucuman
Australia	Research Site	Melbourne
Australia	Research Site	South Brisbane
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Windsor	Ontario
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Shanghai
China	Research Site	Zhengzhou
Denmark	Research Site	Aalborg
Denmark	Research Site	Hellerup
Denmark	Research Site	Hvidovre
Denmark	Research Site	Vejle
Germany	Research Site	Essen
Germany	Research Site	Frankfurt
Germany	Research Site	Gauting
Germany	Research Site	München
India	Research Site	Coimbatore
India	Research Site	Hyderabad
India	Research Site	New Delhi
Italy	Research Site	Milano
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Korea, Republic of	Research Site	Jeonju
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Philippines	Research Site	Quezon City
Poland	Research Site	Bydgoszcz
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Wejherowo
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Ulyanovsk
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Southampton
United States	Research Site	Birmingham	Alabama
United States	Research Site	El Paso	Texas
United States	Research Site	Newport Beach	California
United States	Research Site	Northridge	California
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Hochiminh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Canada,  China,  Denmark,  Germany,  India,  Italy,  Korea, Republic of,  Philippines,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualised exacerbation rate	Annualised exacerbation rate	over the DB treatment period (28 to 52 weeks)
Secondary	Time to first bronchiectasis exacerbation		over the DB treatment period (28 to 52 weeks)
Secondary	Change from baseline in QoL-B-RSS	Quality of Life-Bronchiectasis-Respiratory Symptoms Scale (QoL-B-RSS).; QoL-B-RSS evaluates respiratory symptoms using 9 items from the 37-item QoL-B questionnaire. The QoL-B-RSS is standardized from 0 to 100, with higher scores indicative of better health-related quality of life.	over the DB treatment period (28 to 52 weeks)
Secondary	Change from baseline in pre-dose FEV1	forced expiratory volume in 1 second (FEV1)	over the DB treatment period (28 to 52 weeks)
Secondary	Change from baseline in LCQ	Leicester Cough Questionnaire (LCQ)	over the DB treatment period (28 to 52 weeks)
Secondary	Change from baseline in QoL-B scales (excluding QoL-B-RSS secondary endpoint)	The Quality of Life-Bronchiectasis (QoL-B) is a 37-item questionnaire with 8 scales (Respiratory Symptoms, Physical Functioning, Role Functioning, Emotional Functioning, Social Functioning, Vitality, Health Perceptions, and Treatment Burden Scales).; Each scale is standardized from 0 to 100, with higher scores indicative of better health-related quality of life.	over the DB treatment period (28 to 52 weeks)
Secondary	Change from baseline in SGRQ	St. George's Respiratory Questionnaire (SGRQ)	over the DB treatment period (28 to 52 weeks)
Secondary	Safety and tolerability of benralizumab	Will be evaluated in terms of frequency and rate of: Adverse Events (AEs), abnormal vital signs, abnormal results of clinical laboratory assessments, abnormal findings in physical examinations, and abnormal findings in Electrocardiograms (ECGs).; Assessments related to AEs cover: Occurrence/Frequency; Relationship to IP as assessed by Investigator; Intensity; Seriousness; Death; AEs leading to discontinuation of IP; Other significant AEs	over the DB treatment period (28 to 52 weeks)

External Links

•   MAHALE Poster Master US