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

Recruitment Status:
Active, not recruiting

Sponsor:
AstraZeneca

Information Provided by (Responsible Party):
AstraZeneca

ClinicalTrials.gov Identifier:
NCT05006573

Verification:
Verified 01 August 2022   by AstraZeneca

History of Changes:
ClinicalTrials.gov

Purpose

This is a multicentre, randomised, double-blind, parallel-group, placebo-controlled, 52 week Phase III study 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 52-week double-blind treatment period on investigational product (IP) may be eligible to continue into an open-label extension (OLE), during which all patients will receive benralizumab.

The OLE treatment period is intended to allow patients at least one year of treatment with open label benralizumab.

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)
Study Type:Interventional
Overall Recruitment Status:Active, not recruiting
Study Start Date:21 July 2021
Study Start Date Type:Actual
Primary Completion Date:11 September 2023
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
ConditionInterventionPhase
Non-cystic Fibrosis Bronchiectasis
Biological/Vaccine: Benralizumab
Biological/Vaccine: Placebo to Benralizumab
Phase 3
Ages Eligible for Study: 18 Years  to 130 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
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:
a. Affect the safety of the patient during the study.
b. Influence the findings of the study or their interpretation.
c. 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:
a. 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
b. 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.


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    [email protected]  

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: James  D.  Chalmers , MD   University of Dundee, Nethergate, Dundee DD1 4HN, Scotland, UK

Locations

CountryLocationFacilityContactStatus
KRResearch Site Jeonju-si, KR, 54907Active, not recruiting
KRResearch Site Seoul, KR, 06591Active, not recruiting
KRResearch Site Seoul, KR, 05030Active, not recruiting
KRResearch Site Seoul, KR, 04763Active, not recruiting
KRResearch Site Seoul, KR, 05505Recruiting
KRResearch Site Seoul, KR, 07061Not yet recruiting
DEResearch Site Berlin, DE, 14059Withdrawn
DEResearch Site Borstel, DE, 23845Withdrawn
DEResearch Site Donaustauf, DE, 93093Recruiting
DEResearch Site Düsseldorf, DE, 40489Withdrawn
DEResearch Site Essen, DE, 45239Completed
DEResearch Site Frankfurt, DE, 60590Active, not recruiting
DEResearch Site Gauting, DE, 82131Active, not recruiting
DEResearch Site Hannover, DE, 30625Recruiting
DEResearch Site Heidelberg, DE, 69126Withdrawn
DEResearch Site Hessen, DE, 60596Withdrawn
DEResearch Site München, DE, D-80336Active, not recruiting
PHResearch Site Davao City, PH, PH-8000Not yet recruiting
PHResearch Site Iloilo City, PH, 5000Not yet recruiting
PHResearch Site Manila, PH, 1000Not yet recruiting
PHResearch Site Quezon City, PH, 1100Recruiting
US , CAResearch Site Newport Beach, CA, US, 92663Active, not recruiting
US , CAResearch Site Northridge, CA, US, 91324Active, not recruiting
GBResearch Site Cambridge, GB, CB2 0AYRecruiting
GBResearch Site Dundee, GB, DD1 9SYRecruiting
GBResearch Site Edinburgh, GB, EH16 4SARecruiting
GBResearch Site London, GB, SW3 6NPRecruiting
GBResearch Site Manchester, GB, M23 9LTRecruiting
GBResearch Site Southampton, GB, SO9 4XYRecruiting
US , DCResearch Site Washington, DC, US, 20007Withdrawn
US , MDResearch Site Baltimore, MD, US, 21287Withdrawn
CA , ONResearch Site Ajax, ON, CA, L1S 2J5Recruiting
CA , ONResearch Site Burlington, ON, CA, L7N 3V2Recruiting
CA , ONResearch Site Windsor, ON, CA, N8X-5A6Recruiting
US , MNResearch Site Rochester, MN, US, 55905Withdrawn
ARResearch Site CABA, AR, C1280AEBNot yet recruiting
ARResearch Site CABA, AR, C1012AARRecruiting
ARResearch Site Florida, AR, B1602DQDRecruiting
ARResearch Site San Fernando, AR, B1646EBJRecruiting
ARResearch Site San Miguel de Tucuman, AR, T4000IAQRecruiting
RUResearch Site Chelyabinsk, RU, 454106Suspended
RUResearch Site Penza, RU, 440067Suspended
RUResearch Site Saratov, RU, 410012Suspended
RUResearch Site Tomsk, RU, 634050Withdrawn
RUResearch Site Ulyanovsk, RU, 432009Suspended
ESResearch Site Barcelona, ES, ?08041Recruiting
ESResearch Site Barcelona, ES, 08003Recruiting
ESResearch Site Barcelona, ES, 08035Recruiting
ESResearch Site Madrid, ES, 28040Recruiting
ESResearch Site Valencia, ES, 46017Withdrawn
CA , ABResearch Site Calgary, AB, CA, T2N 4Z6Withdrawn
DKResearch Site Aalborg, DK, 9000Active, not recruiting
DKResearch Site Hellerup, DK, 2900Active, not recruiting
DKResearch Site Hvidovre, DK, 2650Active, not recruiting
DKResearch Site Køge, DK, 4600Withdrawn
DKResearch Site Vejle, DK, 7100Active, not recruiting
INResearch Site Coimbatore, IN, 641028Recruiting
INResearch Site Hyderabad, IN, 500082Recruiting
INResearch Site Jaipur, IN, 302016Withdrawn
INResearch Site Nagpur, IN, 440012Not yet recruiting
INResearch Site New Delhi, IN, 100049Recruiting
INResearch Site Noida, IN, 201 301Recruiting
ITResearch Site Bari, IT, 70124Not yet recruiting
ITResearch Site FOGGIA, IT, 71100Recruiting
ITResearch Site Milano, IT, 20122Recruiting
ITResearch Site Pisa, IT, 56100Recruiting
ITResearch Site Roma, IT, 00168Recruiting
ITResearch Site Rozzano, IT, 20089Recruiting
VNResearch Site Hanoi, VN, 100000Recruiting
VNResearch Site Hanoi, VN, 100000Recruiting
VNResearch Site Hanoi, VN, 100000Not yet recruiting
VNResearch Site Hanoi, VN, 10000Not yet recruiting
VNResearch Site Ho Chi Minh, VN, 700000Recruiting
VNResearch Site Ho Chi Minh, VN, 700000Recruiting
VNResearch Site Hochiminh, VN, 70000Recruiting
VNResearch Site Hochiminh, VN, Not yet recruiting
US , KSResearch Site Kansas City, KS, US, 66160Withdrawn
PLResearch Site Białystok, PL, 15-276Withdrawn
PLResearch Site Bydgoszcz, PL, 85-079Recruiting
PLResearch Site Bydgoszcz, PL, 86-605Not yet recruiting
PLResearch Site Ostrowiec Świętokrzyski, PL, 27-400Recruiting
PLResearch Site Poznań, PL, 60-693Withdrawn
PLResearch Site Wejherowo, PL, 84-200Recruiting
PLResearch Site Wrocław, PL, 54-239Recruiting
US , FLResearch Site Jacksonville, FL, US, 32224Not yet recruiting
US , FLResearch Site Miami, FL, US, 33155Withdrawn
US , FLResearch Site Miami Lakes, FL, US, 33014Withdrawn
US , GAResearch Site Atlanta, GA, US, 30342Not yet recruiting
US , LAResearch Site New Orleans, LA, US, 70112Withdrawn
US , TXResearch Site El Paso, TX, US, 79902Active, not recruiting
US , TXResearch Site Tyler, TX, US, 75708Withdrawn
US , NCResearch Site Statesville, NC, US, 28625Withdrawn
US , NCResearch Site Winston Salem, NC, US, 27103Withdrawn
US , ORResearch Site Portland, OR, US, 97239Withdrawn
CNResearch Site beijing, CN, Recruiting
CNResearch Site Beijing, CN, 100020Not yet recruiting
CNResearch Site Beijing, CN, 102218Not yet recruiting
CNResearch Site Beijing, CN, 100730Not yet recruiting
CNResearch Site Changsha, CN, 430033Recruiting
CNResearch Site fuzhou, CN, 350005Withdrawn
CNResearch Site guangzhou, CN, Recruiting
CNResearch Site Guangzhou, CN, 510080Recruiting
CNResearch Site Guangzhou, CN, 510120Recruiting
CNResearch Site Haikou, CN, 570311Recruiting
CNResearch Site Hohhot, CN, 10050Not yet recruiting
CNResearch Site Nanchang, CN, 330006Not yet recruiting
CNResearch Site Nanchang, CN, 330006Recruiting
CNResearch Site Nanjing, CN, 2100008Not yet recruiting
CNResearch Site Shanghai, CN, 200032Recruiting
CNResearch Site Shanghai, CN, 200433Not yet recruiting
CNResearch Site Tianjin, CN, 300052Recruiting
CNResearch Site Wuhan, CN, 430022Recruiting
CNResearch Site Xuzhou, CN, Withdrawn
CNResearch Site Xuzhou, CN, 221000Not yet recruiting
CNResearch Site Yangzhou, CN, 225001Recruiting
CNResearch Site Zhengzhou, CN, 450000Recruiting
CNResearch Site Zunyi, CN, 563100Recruiting
US , ALResearch Site Birmingham, AL, US, 35233Active, not recruiting
CA , QCResearch Site Quebec, QC, CA, G1V 4G5Withdrawn
US , COResearch Site Denver, CO, US, 80206Not yet recruiting
AUResearch Site Melbourne, AU, 3004Active, not recruiting
AUResearch Site Parkville, AU, 3050Recruiting
AUResearch Site South Brisbane, AU, 4101Active, not recruiting
AUResearch Site Sydney, AU, NSW 2145Recruiting

 File nameDescription
MAHALE Poster Master USMAHALE Poster Master US
.

Purpose

This is a multicentre, randomised, double-blind, parallel-group, placebo-controlled, 52 week Phase III study 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 52-week double-blind treatment period on investigational product (IP) may be eligible to continue into an open-label extension (OLE), during which all patients will receive benralizumab.

The OLE treatment period is intended to allow patients at least one year of treatment with open label benralizumab.

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)
Study Type:Interventional
Overall Recruitment Status:Active, not recruiting
Study Start Date:21 July 2021
Study Start Date Type:Actual
Primary Completion Date:11 September 2023
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
ConditionInterventionPhase
Non-cystic Fibrosis Bronchiectasis
Biological/Vaccine: Benralizumab
Biological/Vaccine: Placebo to Benralizumab
Phase 3
Ages Eligible for Study: 18 Years  to 130 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
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:
a. Affect the safety of the patient during the study.
b. Influence the findings of the study or their interpretation.
c. 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:
a. 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
b. 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.


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    [email protected]  

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: James  D.  Chalmers , MD   University of Dundee, Nethergate, Dundee DD1 4HN, Scotland, UK

Locations

CountryLocationFacilityContactStatus
KRResearch Site Jeonju-si, KR, 54907Active, not recruiting
KRResearch Site Seoul, KR, 06591Active, not recruiting
KRResearch Site Seoul, KR, 05030Active, not recruiting
KRResearch Site Seoul, KR, 04763Active, not recruiting
KRResearch Site Seoul, KR, 05505Recruiting
KRResearch Site Seoul, KR, 07061Not yet recruiting
DEResearch Site Berlin, DE, 14059Withdrawn
DEResearch Site Borstel, DE, 23845Withdrawn
DEResearch Site Donaustauf, DE, 93093Recruiting
DEResearch Site Düsseldorf, DE, 40489Withdrawn
DEResearch Site Essen, DE, 45239Completed
DEResearch Site Frankfurt, DE, 60590Active, not recruiting
DEResearch Site Gauting, DE, 82131Active, not recruiting
DEResearch Site Hannover, DE, 30625Recruiting
DEResearch Site Heidelberg, DE, 69126Withdrawn
DEResearch Site Hessen, DE, 60596Withdrawn
DEResearch Site München, DE, D-80336Active, not recruiting
PHResearch Site Davao City, PH, PH-8000Not yet recruiting
PHResearch Site Iloilo City, PH, 5000Not yet recruiting
PHResearch Site Manila, PH, 1000Not yet recruiting
PHResearch Site Quezon City, PH, 1100Recruiting
US , CAResearch Site Newport Beach, CA, US, 92663Active, not recruiting
US , CAResearch Site Northridge, CA, US, 91324Active, not recruiting
GBResearch Site Cambridge, GB, CB2 0AYRecruiting
GBResearch Site Dundee, GB, DD1 9SYRecruiting
GBResearch Site Edinburgh, GB, EH16 4SARecruiting
GBResearch Site London, GB, SW3 6NPRecruiting
GBResearch Site Manchester, GB, M23 9LTRecruiting
GBResearch Site Southampton, GB, SO9 4XYRecruiting
US , DCResearch Site Washington, DC, US, 20007Withdrawn
US , MDResearch Site Baltimore, MD, US, 21287Withdrawn
CA , ONResearch Site Ajax, ON, CA, L1S 2J5Recruiting
CA , ONResearch Site Burlington, ON, CA, L7N 3V2Recruiting
CA , ONResearch Site Windsor, ON, CA, N8X-5A6Recruiting
US , MNResearch Site Rochester, MN, US, 55905Withdrawn
ARResearch Site CABA, AR, C1280AEBNot yet recruiting
ARResearch Site CABA, AR, C1012AARRecruiting
ARResearch Site Florida, AR, B1602DQDRecruiting
ARResearch Site San Fernando, AR, B1646EBJRecruiting
ARResearch Site San Miguel de Tucuman, AR, T4000IAQRecruiting
RUResearch Site Chelyabinsk, RU, 454106Suspended
RUResearch Site Penza, RU, 440067Suspended
RUResearch Site Saratov, RU, 410012Suspended
RUResearch Site Tomsk, RU, 634050Withdrawn
RUResearch Site Ulyanovsk, RU, 432009Suspended
ESResearch Site Barcelona, ES, ?08041Recruiting
ESResearch Site Barcelona, ES, 08003Recruiting
ESResearch Site Barcelona, ES, 08035Recruiting
ESResearch Site Madrid, ES, 28040Recruiting
ESResearch Site Valencia, ES, 46017Withdrawn
CA , ABResearch Site Calgary, AB, CA, T2N 4Z6Withdrawn
DKResearch Site Aalborg, DK, 9000Active, not recruiting
DKResearch Site Hellerup, DK, 2900Active, not recruiting
DKResearch Site Hvidovre, DK, 2650Active, not recruiting
DKResearch Site Køge, DK, 4600Withdrawn
DKResearch Site Vejle, DK, 7100Active, not recruiting
INResearch Site Coimbatore, IN, 641028Recruiting
INResearch Site Hyderabad, IN, 500082Recruiting
INResearch Site Jaipur, IN, 302016Withdrawn
INResearch Site Nagpur, IN, 440012Not yet recruiting
INResearch Site New Delhi, IN, 100049Recruiting
INResearch Site Noida, IN, 201 301Recruiting
ITResearch Site Bari, IT, 70124Not yet recruiting
ITResearch Site FOGGIA, IT, 71100Recruiting
ITResearch Site Milano, IT, 20122Recruiting
ITResearch Site Pisa, IT, 56100Recruiting
ITResearch Site Roma, IT, 00168Recruiting
ITResearch Site Rozzano, IT, 20089Recruiting
VNResearch Site Hanoi, VN, 100000Recruiting
VNResearch Site Hanoi, VN, 100000Recruiting
VNResearch Site Hanoi, VN, 100000Not yet recruiting
VNResearch Site Hanoi, VN, 10000Not yet recruiting
VNResearch Site Ho Chi Minh, VN, 700000Recruiting
VNResearch Site Ho Chi Minh, VN, 700000Recruiting
VNResearch Site Hochiminh, VN, 70000Recruiting
VNResearch Site Hochiminh, VN, Not yet recruiting
US , KSResearch Site Kansas City, KS, US, 66160Withdrawn
PLResearch Site Białystok, PL, 15-276Withdrawn
PLResearch Site Bydgoszcz, PL, 85-079Recruiting
PLResearch Site Bydgoszcz, PL, 86-605Not yet recruiting
PLResearch Site Ostrowiec Świętokrzyski, PL, 27-400Recruiting
PLResearch Site Poznań, PL, 60-693Withdrawn
PLResearch Site Wejherowo, PL, 84-200Recruiting
PLResearch Site Wrocław, PL, 54-239Recruiting
US , FLResearch Site Jacksonville, FL, US, 32224Not yet recruiting
US , FLResearch Site Miami, FL, US, 33155Withdrawn
US , FLResearch Site Miami Lakes, FL, US, 33014Withdrawn
US , GAResearch Site Atlanta, GA, US, 30342Not yet recruiting
US , LAResearch Site New Orleans, LA, US, 70112Withdrawn
US , TXResearch Site El Paso, TX, US, 79902Active, not recruiting
US , TXResearch Site Tyler, TX, US, 75708Withdrawn
US , NCResearch Site Statesville, NC, US, 28625Withdrawn
US , NCResearch Site Winston Salem, NC, US, 27103Withdrawn
US , ORResearch Site Portland, OR, US, 97239Withdrawn
CNResearch Site beijing, CN, Recruiting
CNResearch Site Beijing, CN, 100020Not yet recruiting
CNResearch Site Beijing, CN, 102218Not yet recruiting
CNResearch Site Beijing, CN, 100730Not yet recruiting
CNResearch Site Changsha, CN, 430033Recruiting
CNResearch Site fuzhou, CN, 350005Withdrawn
CNResearch Site guangzhou, CN, Recruiting
CNResearch Site Guangzhou, CN, 510080Recruiting
CNResearch Site Guangzhou, CN, 510120Recruiting
CNResearch Site Haikou, CN, 570311Recruiting
CNResearch Site Hohhot, CN, 10050Not yet recruiting
CNResearch Site Nanchang, CN, 330006Not yet recruiting
CNResearch Site Nanchang, CN, 330006Recruiting
CNResearch Site Nanjing, CN, 2100008Not yet recruiting
CNResearch Site Shanghai, CN, 200032Recruiting
CNResearch Site Shanghai, CN, 200433Not yet recruiting
CNResearch Site Tianjin, CN, 300052Recruiting
CNResearch Site Wuhan, CN, 430022Recruiting
CNResearch Site Xuzhou, CN, Withdrawn
CNResearch Site Xuzhou, CN, 221000Not yet recruiting
CNResearch Site Yangzhou, CN, 225001Recruiting
CNResearch Site Zhengzhou, CN, 450000Recruiting
CNResearch Site Zunyi, CN, 563100Recruiting
US , ALResearch Site Birmingham, AL, US, 35233Active, not recruiting
CA , QCResearch Site Quebec, QC, CA, G1V 4G5Withdrawn
US , COResearch Site Denver, CO, US, 80206Not yet recruiting
AUResearch Site Melbourne, AU, 3004Active, not recruiting
AUResearch Site Parkville, AU, 3050Recruiting
AUResearch Site South Brisbane, AU, 4101Active, not recruiting
AUResearch Site Sydney, AU, NSW 2145Recruiting

Oversight


Is IND/IDE protocol: Yes 
IND/IDE Grantor: CDER 
IND/IDE Number: 147212 
Has Expanded Access: No 
U.S. FDA-regulated Drug: Yes 
U.S. FDA-regulated Device: No 

More Information


MAHALE Poster Master US

No publications provided

Responsible Party:AstraZeneca
ClinicalTrials.gov Identifier:NCT05006573
Other Study ID Numbers:D325BC00001, 2020-004068-24

Keywords provided by AstraZeneca
Benralizumab
Non-cystic Fibrosis Bronchiectasis
Eosinophlic Inflammation

Additional Relevant MeSH terms:
Non-cystic Fibrosis Bronchiectasis

Primary Outcome Measures:

  • Annualised exacerbation rate [ Time Frame: Over first 52 weeks ] [ Designated as safety issue:  ]
    Annualised exacerbation rate

Secondary Outcome Measures:

  • Time to first bronchiectasis exacerbation [ Time Frame: During first 52 weeks ] [ Designated as safety issue:  ]

  • Change from baseline in QoL-B-RSS [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    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.

  • Change from baseline in pre-dose FEV1 [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    forced expiratory volume in 1 second (FEV1)

  • Change from baseline in LCQ [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    Leicester Cough Questionnaire (LCQ)

  • Annualised rate of severe bronchiectasis exacerbations [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    Annualised rate of severe bronchiectasis exacerbations.

    An exacerbation will be considered severe if it results in hospitalisation or death.

  • Annualised rate of hospitalisations due to bronchiectasis exacerbations [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    annual rate of hospitalisation due to exacerbation

  • Frequency of antibiotic use for bronchiectasis exacerbations [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    Number of times an antibiotic is given

  • Change from baseline in QoL-B scales (excluding QoL-B-RSS key secondary endpoint) [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    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.

  • Change from baseline in SGRQ [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    St. George's Respiratory Questionnaire (SGRQ)

  • Frequency and annual rate of NCFB-related healthcare encounters [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    Frequency and annual rate of healthcare encounters (hospitalisation, ICU stay, emergency room visits, urgent care, specialist/GP visits, home healthcare)

    general practitioner (GP)
    intensive care unit (ICU)

  • Frequency and annual rate of NCFB-related tests/procedures [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    Frequency and annual rate of NCFB-related procedures/tests

  • Total hospital length of stay per healthcare encounter [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    Hospital length of stay in days

  • Safety and tolerability of benralizumab [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    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

Other Pre-specified Outcome Measures:

  • Serum benralizumab concentration as a measure of pharmacokinetics [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    Pharmacokinetic outcome measure is serum concentration of benralizumab measured at through (Cmin). The objective is to evaluate the PK exposure of benralizumab in patients.

  • Anti-drug antibodies (ADA) as a measure of immunogenicity [ Time Frame: over 52 weeks ] [ Designated as safety issue:  ]
    Immunogenicity of benralizumab will be assessed by Anti-benralizumab antibodies.
    The following anti-drug antibodies (ADA) responses will be evaluated for each patient:
    ADA prevalence (positive at baseline and/or post-baseline)
    % of patients who are ADA negative at all assessments
    % of patients who are ADA positive at baseline only,
    % of patients who are ADA positive at baseline and at least one post-baseline
    ADA incidence (treatment-emergent positive)
    ADA persistently positive
    ADA transiently positive
    ADA positive with maximum titre > median of maximum titres

ArmsAssigned Interventions
Experimental: Benralizumab
Benralizumab will be administered subcutaneously (SC) using an accessorized prefilled syringe (APFS)
Biological/Vaccine: Benralizumab
Benralizumab active solution in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume
 
Placebo Comparator: Placebo
Matching placebo solution will be administered subcutaneously (SC) using an accessorized prefilled syringe (APFS)
Biological/Vaccine: Placebo to Benralizumab
Matching placebo solution in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume