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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05006573




Registration number
NCT05006573
Ethics application status
Date submitted
23/06/2021
Date registered
16/08/2021

Titles & IDs
Public title
Efficacy and Safety of Benralizumab in Patients With Non-cystic Fibrosis Bronchiectasis
Scientific 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)
Secondary ID [1] 0 0
2020-004068-24
Secondary ID [2] 0 0
D325BC00001
Universal Trial Number (UTN)
Trial acronym
MAHALE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-cystic Fibrosis Bronchiectasis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Benralizumab
Treatment: Other - Placebo to Benralizumab

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

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


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

Treatment: Other: Placebo to Benralizumab
Matching placebo solution in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualised exacerbation rate
Timepoint [1] 0 0
over the DB treatment period (28 to 52 weeks)
Secondary outcome [1] 0 0
Time to first bronchiectasis exacerbation
Timepoint [1] 0 0
over the DB treatment period (28 to 52 weeks)
Secondary outcome [2] 0 0
Change from baseline in QoL-B-RSS
Timepoint [2] 0 0
over the DB treatment period (28 to 52 weeks)
Secondary outcome [3] 0 0
Change from baseline in pre-dose FEV1
Timepoint [3] 0 0
over the DB treatment period (28 to 52 weeks)
Secondary outcome [4] 0 0
Change from baseline in LCQ
Timepoint [4] 0 0
over the DB treatment period (28 to 52 weeks)
Secondary outcome [5] 0 0
Change from baseline in QoL-B scales (excluding QoL-B-RSS secondary endpoint)
Timepoint [5] 0 0
over the DB treatment period (28 to 52 weeks)
Secondary outcome [6] 0 0
Change from baseline in SGRQ
Timepoint [6] 0 0
over the DB treatment period (28 to 52 weeks)
Secondary outcome [7] 0 0
Safety and tolerability of benralizumab
Timepoint [7] 0 0
over the DB treatment period (28 to 52 weeks)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/04/2024
Sample size
Target
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment hospital [2] 0 0
Research Site - South Brisbane
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Argentina
State/province [4] 0 0
Florida
Country [5] 0 0
Argentina
State/province [5] 0 0
San Fernando
Country [6] 0 0
Argentina
State/province [6] 0 0
San Miguel de Tucuman
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
China
State/province [8] 0 0
Guangzhou
Country [9] 0 0
China
State/province [9] 0 0
Shanghai
Country [10] 0 0
China
State/province [10] 0 0
Zhengzhou
Country [11] 0 0
Denmark
State/province [11] 0 0
Aalborg
Country [12] 0 0
Denmark
State/province [12] 0 0
Hellerup
Country [13] 0 0
Denmark
State/province [13] 0 0
Hvidovre
Country [14] 0 0
Denmark
State/province [14] 0 0
Vejle
Country [15] 0 0
Germany
State/province [15] 0 0
Essen
Country [16] 0 0
Germany
State/province [16] 0 0
Frankfurt
Country [17] 0 0
Germany
State/province [17] 0 0
Gauting
Country [18] 0 0
Germany
State/province [18] 0 0
München
Country [19] 0 0
India
State/province [19] 0 0
Coimbatore
Country [20] 0 0
India
State/province [20] 0 0
Hyderabad
Country [21] 0 0
India
State/province [21] 0 0
New Delhi
Country [22] 0 0
Italy
State/province [22] 0 0
Milano
Country [23] 0 0
Italy
State/province [23] 0 0
Pisa
Country [24] 0 0
Italy
State/province [24] 0 0
Roma
Country [25] 0 0
Italy
State/province [25] 0 0
Rozzano
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Jeonju
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Philippines
State/province [28] 0 0
Quezon City
Country [29] 0 0
Poland
State/province [29] 0 0
Bydgoszcz
Country [30] 0 0
Poland
State/province [30] 0 0
Ostrowiec Swietokrzyski
Country [31] 0 0
Poland
State/province [31] 0 0
Wejherowo
Country [32] 0 0
Poland
State/province [32] 0 0
Wroclaw
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Penza
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Saratov
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Ulyanovsk
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Cambridge
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Dundee
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Edinburgh
Country [41] 0 0
United Kingdom
State/province [41] 0 0
London
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Manchester
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Southampton
Country [44] 0 0
Vietnam
State/province [44] 0 0
Hanoi
Country [45] 0 0
Vietnam
State/province [45] 0 0
Ho Chi Minh
Country [46] 0 0
Vietnam
State/province [46] 0 0
Hochiminh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James D. Chalmers, MD
Address 0 0
University of Dundee, Nethergate, Dundee DD1 4HN, Scotland, UK
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05006573