Clinical Trials List
Protocol NumberD3250C00036
NCT Number(ClinicalTrials.gov Identfier)NCT03186209
2017-07-01 - 2021-07-22
Phase III
Recruiting4
ICD-10J45.909
Unspecified asthma, uncomplicated
A Multicentre, Randomised, Double-blind, Parallel Group, Placebocontrolled, Phase 3 Efficacy and Safety Study of Benralizumab (MEDI-563) Added to Medium to High-dose Inhaled Corticosteroid Plus Long-acting β2 Agonist in Patients With Uncontrolled Asthma.
-
Trial Applicant
-
Sponsor
AstraZeneca
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Horng-Chyuan Lin Division of Thoracic Medicine
- 王才郁 Division of Thoracic Medicine
- KUO-WEI YEH Division of Pediatrics
- Han-Pin Kuo Division of Thoracic Medicine
- Jing-Long Huang Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 周昆達 Division of Thoracic Medicine
- 蕭逸函 Division of Thoracic Medicine
- Hsin-Kuo Ko Division of Thoracic Medicine
- 林芳綺 Division of Thoracic Medicine
- Kang-Cheng Su Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Asthma
Objectives
Primary Objective:
To evaluate the effect of benralizumab on
asthma exacerbations in patients on
medium to high-dose ICS-LABA with
uncontrolled asthma.
Secondary Objectives:
-To assess the effect of benralizumab on
pulmonary function
-To assess the effect of benralizumab on
asthma symptoms and other asthma control
metrics (as per the ePRO)
-To assess the effect of benralizumab on
other parameters associated with asthma
exacerbations
-To assess the effect of benralizumab on
health-related quality of life
-To assess the effect of benralizumab on
emergency room/urgent care visits and
hospitalizations due to asthma
-To evaluate the effect of benralizumab on
health care resource utilization
-To evaluate the pharmacokinetics and
immunogenicity of benralizumab
-To assess the impact of benralizumab on
blood eosinophil levels
Safety Objective:
To assess the safety and tolerability of
benralizumab
Test Drug
Benralizumab
Active Ingredient
Benralizumab
Dosage Form
injection
Dosage
30
Endpoints
Annual asthma exacerbation rate, where an
asthma exacerbation is defined in Section 5.1.1
by a worseninga
of asthma requiring:
Use of systemic corticosteroids (or a
temporary increase in a stable oral
corticosteroid background dose) for at least 3
days; a single depo-injectable dose of
corticosteroids will be considered equivalent
to a 3-day course of systemic corticosteroids
An emergency room/urgent care visit
(defined as evaluation and treatment for < 24
hours in an Emergency department (ED) or
urgent care centre) due to asthma that
required systemic corticosteroids (as per
above)
An inpatient hospitalization due to asthma
(defined as an admission to an inpatient
facility and/or evaluation and treatment in a
healthcare facility for≥ 24 hours)
asthma exacerbation is defined in Section 5.1.1
by a worseninga
of asthma requiring:
Use of systemic corticosteroids (or a
temporary increase in a stable oral
corticosteroid background dose) for at least 3
days; a single depo-injectable dose of
corticosteroids will be considered equivalent
to a 3-day course of systemic corticosteroids
An emergency room/urgent care visit
(defined as evaluation and treatment for < 24
hours in an Emergency department (ED) or
urgent care centre) due to asthma that
required systemic corticosteroids (as per
above)
An inpatient hospitalization due to asthma
(defined as an admission to an inpatient
facility and/or evaluation and treatment in a
healthcare facility for≥ 24 hours)
Inclution Criteria
Inclusion criteria
For inclusion in the study patients should fulfil all of the following criteria:
1. Written informed consent, and assent when applicable for study participation must
be obtained prior to any study related procedures being performed (local regulations
are to be followed in determining the assent/consent requirements for children and
parent[s]/guardian[s]) and according to international guidelines and/or applicable
European Union guidelines.
2. Female and male aged 12 to 75 years, inclusively, at the time of Visit 1
For those patients, who are 17 on the day of Visit 1 but will turn 18 after this
day, will be considered an adolescent for the purposes of this trial
3. Women of childbearing potential (WOCBP) must use an effective form of birth
control (confirmed by the Investigator or designee). Highly effective forms of birth
control includes: true sexual abstinence, a vasectomised sexual partner, Implanon,
female sterilization by tubal occlusion, any effective IUD Intrauterine device/IUS
Ievonorgestrel Intrauterine system, Depo-Provera™ injections, oral contraceptive,
and Evra Patch ™ or Nuvaring™. WOCBP must agree to use an effective method
of birth control, as defined above, from enrolment, throughout the study duration
and within 16 weeks after last dose of IP, and have negative serum pregnancy test
result on Visit 1.
Women not of childbearing potential are defined as women who are either
permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy), or who are postmenopausal. Women will be considered
postemenopausal if they have been amenorrheic for 12 months prior to the planned
date of randomization without an alternative medical cause. The following agespecific requirements apply:
Women <50 years old would be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous
hormonal treatment and follicle stimulating hormone (FSH) levels in the
postmenopausal range.
Women ≥50 years old would be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous
hormonal treatment.
4. All male patients who are sexually active must agree to use a double barrier method
of contraception (condom with spermicide) from the first dose of IP until 16 weeks
after their last dose.
5. Weight of ≥40 kg.
6. History of physician-diagnosed asthma requiring treatment with medium-to-high
dose ICS (>250μg fluticasone dry powder formulation equivalents total daily dose)
and a LABA, for at least 6 months prior to Visit 1. Equivalents for fluticasone dry
powder can be found in Appendix E Background Therapy Equivalence Table.
7. Additional maintenance asthma controller medications that are locally approved in a
country for the treatment of asthma (eg, LTRAs, tiotropium, cromone, theophylline,
oral corticosteroid), and have been used for at least 30 days prior to Visit 1 are
allowed.
8. At least 2 documented asthma exacerbations in the 12 months prior to the date
informed consent, and assent, at least 1 of the 2 exacerbations should occur during
the treatment of medium-to-high dose ICS-LABA, when applicable is obtained that
required use of a systemic corticosteroid or a temporary increase from the patient’s
usual maintenance dose of oral corticosteroid (please refer to Section 4.1.1). For
patients who are re-screened within 30 days of their screen failure date, the
calculation of the 12 month period should be done from the original informed
consent, and assent when applicable date.
9. Documented post-bronchodilator (post-BD) reversibility in FEV1 of >12% and
>200 mL in FEV1 within 12 months prior to Visit 1. If historical documentation is
not available, reversibility must be demonstrated and documented at Visit 2.
Inclusion criteria at randomization
10. For WOCBP only: have a negative urine pregnancy test prior to administration of
the IP at Visit 4.
11. Fulfilment of at least 1 of the following conditions over the 7 days prior to
randomization:
>2 days with a daytime or night time symptoms score >1
Rescue SABA use on >2 days
≥1 nocturnal awakening due to asthma
12. Patients demonstrate acceptable inhaler, peak flow meter, and spirometry
techniques during run-in (from Visit 2 to Visit 4)
13. At least 70% compliance with usual asthma controller ICS-LABA during over the
14 days prior to randomization based on Asthma Daily Diary. Patients who
experience an asthma exacerbation during run-in may temporarily be unable to
complete their diary due to illness or hospitalization. In these cases, ICS-LABA
compliance will be calculated for the period after systemic corticosteroid therapy is
complete.
14. At least 70% compliance with ePRO completion
At least 70% compliance defined as completing Asthma Daily Diary for any 10
complete days (i.e., consecutive evening and morning, for example, Day -14
evening + Day -13 morning) of the last 14 days of the run-in period.
For inclusion in the study patients should fulfil all of the following criteria:
1. Written informed consent, and assent when applicable for study participation must
be obtained prior to any study related procedures being performed (local regulations
are to be followed in determining the assent/consent requirements for children and
parent[s]/guardian[s]) and according to international guidelines and/or applicable
European Union guidelines.
2. Female and male aged 12 to 75 years, inclusively, at the time of Visit 1
For those patients, who are 17 on the day of Visit 1 but will turn 18 after this
day, will be considered an adolescent for the purposes of this trial
3. Women of childbearing potential (WOCBP) must use an effective form of birth
control (confirmed by the Investigator or designee). Highly effective forms of birth
control includes: true sexual abstinence, a vasectomised sexual partner, Implanon,
female sterilization by tubal occlusion, any effective IUD Intrauterine device/IUS
Ievonorgestrel Intrauterine system, Depo-Provera™ injections, oral contraceptive,
and Evra Patch ™ or Nuvaring™. WOCBP must agree to use an effective method
of birth control, as defined above, from enrolment, throughout the study duration
and within 16 weeks after last dose of IP, and have negative serum pregnancy test
result on Visit 1.
Women not of childbearing potential are defined as women who are either
permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy), or who are postmenopausal. Women will be considered
postemenopausal if they have been amenorrheic for 12 months prior to the planned
date of randomization without an alternative medical cause. The following agespecific requirements apply:
Women <50 years old would be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous
hormonal treatment and follicle stimulating hormone (FSH) levels in the
postmenopausal range.
Women ≥50 years old would be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous
hormonal treatment.
4. All male patients who are sexually active must agree to use a double barrier method
of contraception (condom with spermicide) from the first dose of IP until 16 weeks
after their last dose.
5. Weight of ≥40 kg.
6. History of physician-diagnosed asthma requiring treatment with medium-to-high
dose ICS (>250μg fluticasone dry powder formulation equivalents total daily dose)
and a LABA, for at least 6 months prior to Visit 1. Equivalents for fluticasone dry
powder can be found in Appendix E Background Therapy Equivalence Table.
7. Additional maintenance asthma controller medications that are locally approved in a
country for the treatment of asthma (eg, LTRAs, tiotropium, cromone, theophylline,
oral corticosteroid), and have been used for at least 30 days prior to Visit 1 are
allowed.
8. At least 2 documented asthma exacerbations in the 12 months prior to the date
informed consent, and assent, at least 1 of the 2 exacerbations should occur during
the treatment of medium-to-high dose ICS-LABA, when applicable is obtained that
required use of a systemic corticosteroid or a temporary increase from the patient’s
usual maintenance dose of oral corticosteroid (please refer to Section 4.1.1). For
patients who are re-screened within 30 days of their screen failure date, the
calculation of the 12 month period should be done from the original informed
consent, and assent when applicable date.
9. Documented post-bronchodilator (post-BD) reversibility in FEV1 of >12% and
>200 mL in FEV1 within 12 months prior to Visit 1. If historical documentation is
not available, reversibility must be demonstrated and documented at Visit 2.
Inclusion criteria at randomization
10. For WOCBP only: have a negative urine pregnancy test prior to administration of
the IP at Visit 4.
11. Fulfilment of at least 1 of the following conditions over the 7 days prior to
randomization:
>2 days with a daytime or night time symptoms score >1
Rescue SABA use on >2 days
≥1 nocturnal awakening due to asthma
12. Patients demonstrate acceptable inhaler, peak flow meter, and spirometry
techniques during run-in (from Visit 2 to Visit 4)
13. At least 70% compliance with usual asthma controller ICS-LABA during over the
14 days prior to randomization based on Asthma Daily Diary. Patients who
experience an asthma exacerbation during run-in may temporarily be unable to
complete their diary due to illness or hospitalization. In these cases, ICS-LABA
compliance will be calculated for the period after systemic corticosteroid therapy is
complete.
14. At least 70% compliance with ePRO completion
At least 70% compliance defined as completing Asthma Daily Diary for any 10
complete days (i.e., consecutive evening and morning, for example, Day -14
evening + Day -13 morning) of the last 14 days of the run-in period.
Exclusion Criteria
Exclusion criteria
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Clinically important pulmonary disease other than asthma (eg, active lung infection,
COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation
syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and
primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic
disease, other than asthma, that are associated with elevated peripheral eosinophil
counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss
syndrome, hypereosinophilic syndrome).
2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic,
renal, neurological, musculoskeletal, infectious, endocrine, metabolic,
haematological, psychiatric, or major physical impairment that is not stable in the
opinion of the Investigator and could:
Affect the safety of the patient throughout the study
Influence the findings of the studies or their interpretations
Impede the patient’s ability to complete the entire duration of study.
3. Known history of allergy or reaction to the investigational product (IP) formulation.
4. History of anaphylaxis to any biologic therapy.
5. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed
consent, and assent when applicable, is obtained that has not been treated with, or
has failed to respond to standard of care therapy.
6. Acute upper or lower respiratory infections requiring antibiotics or antiviral
medication within 30 days prior to the date informed consent, and assent when
applicable, is obtained or during the screening period.
7. Any clinically significant abnormal findings in physical examination, vital signs,
haematology, clinical chemistry, or urinalysis during screening period, which in the
opinion of the Investigator, may put the patient at risk because of his/her
participation in the study, or may influence the results of the study, or the patient’s
ability to complete entire duration of the study.
8. Any clinically significant cardiac disease (such as but not limited to unstable
ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial
infarction) or any ECG abnormality obtained during the screening period, which in
the opinion of the investigator may put the patient at risk or interfere with study
assessments.
9. History of alcohol or drug abuse within 12 months prior to the date informed
consent, and assent when applicable is obtained.
10. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a
positive medical history for hepatitis B or C. Patients with a history of hepatitis B
vaccination without history of hepatitis B are allowed to enroll.
11. A history of known immunodeficiency disorder including a positive human
immunodeficiency virus (HIV) test.
12. Current smokers or former smokers with a smoking history of > 10 pack-years.
13. History of cancer:
Patients who have had basal cell carcinoma, localized squamous cell carcinoma
of the skin, or in situ carcinoma of the cervix are eligible provided that the
patient is in remission and curative therapy was completed at least 12 months
prior to the date informed consent, and assent when applicable was obtained,
Patients who have had other malignancies are eligible provided that the patient
is in remission and curative therapy was completed at least 5 years prior to the
date informed consent, and assent when applicable, was obtained.
14. Use of immunosuppressive medication (including but not limited to: methotrexate,
troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot
corticosteroid, or any experimental anti-inflammatory therapy) within 3 months
prior to the date informed consent, and assent when applicable, is obtained. Chronic
maintenance prednisone for the treatment of asthma is allowed.
15. Receipt of immunoglobulin or blood products within 30 days prior to the date
informed consent, and assent when applicable, is obtained.
16. Receipt of any marketed (eg omalizumab) or investigational biologic within 4
months or 5 half-lives prior to the date informed consent, and assent when
applicable, is obtained, whichever is longer.
17. Receipt of live attenuated vaccines 30 days prior to the date of randomization:
within 4 months or within 5 half-lives prior to the date informed consent and assent
is obtained, whichever is longer:
Receipt of inactive/killed vaccinations (eg, inactive influenza) are allowed
provided they are not administered within 1 week before/after any IP
administration.
18. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to
randomization, whichever is longer. Use of any off-label medications, for example
medications locally approved for Chronic Obstructive Pulmonary Disease but not
for asthma, are also not allowed from 30 days prior to randomization and
throughout the study.
19. Previously randomised in any benralizumab (MEDI-563) study, including the
present study.
20. Initiation of new allergen immunotherapy is not allowed within 30 days prior to the
date of informed consent, and assent when applicable. Immunotherapy initiated
prior to this period or as a routine part of the patient’s seasonal treatment is allowed.
If the immunotherapy is delivered as an injection, there should be a gap of 7 days
between the immunotherapy and IP administration.
21. Current use of any oral or ophthalmic non-selective β-adrenergic antagonist (eg,
propranolol).
22. Planned surgical procedures during the conduct of the study.
23. Currently breastfeeding or lactating women.
24. Concurrent enrolment in another clinical trial.
25. AstraZeneca staff involved in the planning and/or conduct of the study.
26. Employees of the study centre or any other individuals involved with the conduct of
the study, or immediate family members of such individuals.
27. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5
times the upper limit of normal (ULN) confirmed during screening period.
28. Five-lipoxygenase inhibitors (eg, Zileuton) and roflumilast are prohibited.
29. Received bronchial thermoplasty (BT) as treatment of asthma within 12 months
prior to Visit 1.
For procedures for withdrawal of incorrectly enrolled or randomised patients see Section 3.4.
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Clinically important pulmonary disease other than asthma (eg, active lung infection,
COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation
syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and
primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic
disease, other than asthma, that are associated with elevated peripheral eosinophil
counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss
syndrome, hypereosinophilic syndrome).
2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic,
renal, neurological, musculoskeletal, infectious, endocrine, metabolic,
haematological, psychiatric, or major physical impairment that is not stable in the
opinion of the Investigator and could:
Affect the safety of the patient throughout the study
Influence the findings of the studies or their interpretations
Impede the patient’s ability to complete the entire duration of study.
3. Known history of allergy or reaction to the investigational product (IP) formulation.
4. History of anaphylaxis to any biologic therapy.
5. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed
consent, and assent when applicable, is obtained that has not been treated with, or
has failed to respond to standard of care therapy.
6. Acute upper or lower respiratory infections requiring antibiotics or antiviral
medication within 30 days prior to the date informed consent, and assent when
applicable, is obtained or during the screening period.
7. Any clinically significant abnormal findings in physical examination, vital signs,
haematology, clinical chemistry, or urinalysis during screening period, which in the
opinion of the Investigator, may put the patient at risk because of his/her
participation in the study, or may influence the results of the study, or the patient’s
ability to complete entire duration of the study.
8. Any clinically significant cardiac disease (such as but not limited to unstable
ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial
infarction) or any ECG abnormality obtained during the screening period, which in
the opinion of the investigator may put the patient at risk or interfere with study
assessments.
9. History of alcohol or drug abuse within 12 months prior to the date informed
consent, and assent when applicable is obtained.
10. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a
positive medical history for hepatitis B or C. Patients with a history of hepatitis B
vaccination without history of hepatitis B are allowed to enroll.
11. A history of known immunodeficiency disorder including a positive human
immunodeficiency virus (HIV) test.
12. Current smokers or former smokers with a smoking history of > 10 pack-years.
13. History of cancer:
Patients who have had basal cell carcinoma, localized squamous cell carcinoma
of the skin, or in situ carcinoma of the cervix are eligible provided that the
patient is in remission and curative therapy was completed at least 12 months
prior to the date informed consent, and assent when applicable was obtained,
Patients who have had other malignancies are eligible provided that the patient
is in remission and curative therapy was completed at least 5 years prior to the
date informed consent, and assent when applicable, was obtained.
14. Use of immunosuppressive medication (including but not limited to: methotrexate,
troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot
corticosteroid, or any experimental anti-inflammatory therapy) within 3 months
prior to the date informed consent, and assent when applicable, is obtained. Chronic
maintenance prednisone for the treatment of asthma is allowed.
15. Receipt of immunoglobulin or blood products within 30 days prior to the date
informed consent, and assent when applicable, is obtained.
16. Receipt of any marketed (eg omalizumab) or investigational biologic within 4
months or 5 half-lives prior to the date informed consent, and assent when
applicable, is obtained, whichever is longer.
17. Receipt of live attenuated vaccines 30 days prior to the date of randomization:
within 4 months or within 5 half-lives prior to the date informed consent and assent
is obtained, whichever is longer:
Receipt of inactive/killed vaccinations (eg, inactive influenza) are allowed
provided they are not administered within 1 week before/after any IP
administration.
18. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to
randomization, whichever is longer. Use of any off-label medications, for example
medications locally approved for Chronic Obstructive Pulmonary Disease but not
for asthma, are also not allowed from 30 days prior to randomization and
throughout the study.
19. Previously randomised in any benralizumab (MEDI-563) study, including the
present study.
20. Initiation of new allergen immunotherapy is not allowed within 30 days prior to the
date of informed consent, and assent when applicable. Immunotherapy initiated
prior to this period or as a routine part of the patient’s seasonal treatment is allowed.
If the immunotherapy is delivered as an injection, there should be a gap of 7 days
between the immunotherapy and IP administration.
21. Current use of any oral or ophthalmic non-selective β-adrenergic antagonist (eg,
propranolol).
22. Planned surgical procedures during the conduct of the study.
23. Currently breastfeeding or lactating women.
24. Concurrent enrolment in another clinical trial.
25. AstraZeneca staff involved in the planning and/or conduct of the study.
26. Employees of the study centre or any other individuals involved with the conduct of
the study, or immediate family members of such individuals.
27. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5
times the upper limit of normal (ULN) confirmed during screening period.
28. Five-lipoxygenase inhibitors (eg, Zileuton) and roflumilast are prohibited.
29. Received bronchial thermoplasty (BT) as treatment of asthma within 12 months
prior to Visit 1.
For procedures for withdrawal of incorrectly enrolled or randomised patients see Section 3.4.
The Estimated Number of Participants
-
Taiwan
65 participants
-
Global
1005 participants
