Efficacy and Safety Study of Benralizumab in Patients With Uncontrolled Asthma on Medium to High Dose Inhaled Corticosteroid Plus LABA (MIRACLE)
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.
2 other identifiers
interventional
695
4 countries
79
Brief Summary
This is a randomised, double-blind, parallel group, placebo-controlled study designed to evaluate the efficacy and safety of a fixed 30 mg dose of benralizumab administered subcutaneously for patients with a history of asthma exacerbations and uncontrolled asthma receiving medium to high-dose inhaled corticosteroid plus long-acting β2-agonist (ICS-LABA) with or without oral corticosteroids and additional asthma controllers.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 asthma
Started Sep 2017
Longer than P75 for phase_3 asthma
79 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 19, 2017
CompletedFirst Posted
Study publicly available on registry
June 14, 2017
CompletedStudy Start
First participant enrolled
September 7, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2023
CompletedResults Posted
Study results publicly available
April 24, 2024
CompletedApril 24, 2024
March 1, 2024
5.4 years
May 19, 2017
September 14, 2023
March 28, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Annual Asthma Exacerbation Rate in Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma for Baseline Eosinophils >=300/uL
Annual asthma exacerbation rate over the 48-week treatment period among benralizumab and placebo groups
From randomization through Study Week 48
Secondary Outcomes (15)
Change From Baseline at Week 48 in Pre-bronchodilator FEV1 (L) Value for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL
From randomization through Study Week 48
Change From Baseline at Week 48 in Total Asthma Symptom Score for for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL
From randomization through Study Week 48
Change From Baseline at Week 48 in Total Asthma Rescue Medication Use for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL
From randomization through Study Week 48
Change From Baseline at Week 48 in Morning Peak Expiratory Flow (PEF) for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL
From randomization through Study Week 48
Change From Baseline at Week 48 in Evening Peak Expiratory Flow (PEF) for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL
From randomization through Study Week 48
- +10 more secondary outcomes
Other Outcomes (3)
Annual Asthma Exacerbation Rate in Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils <300/uL
From randomization through Study Week 48.
Change From Baseline at Week 48 in Pre-bronchodilator FEV1 (L) Value for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils <300/uL
From randomization through Study Week 48
Change From Baseline at Week 48 in Total Asthma Symptom Score for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils <300/uL
From randomization through Study Week 48
Study Arms (2)
Benralizumab
EXPERIMENTALBenralizumab administered subcutaneously
Placebo
PLACEBO COMPARATORPlacebo administered subcutaneously
Interventions
Benralizumab subcutaneously on study week 0 until study week 40 inclusive.
Eligibility Criteria
You may qualify if:
- 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 local guidelines.
- 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.
- History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (\>250μg fluticasone propionate dry powder formulation equivalents total daily dose) and a LABA, for at least 6 months prior to Visit 1.
- Additional maintenance asthma controller medications that are locally approved in a country for the treatment of asthma (e.g., leukotriene receptor antagonists (LTRAs), tiotropium, chromone, theophylline, oral corticosteroid), and have been used for at least 30 days prior to Visit 1 are allowed.
- At least 2 documented asthma exacerbations in the 12 months prior to the date informed consent, and assent when available, during the treatment of medium-to-high dose ICS-LABA that required use of a systemic corticosteroid or a temporary increase from the patient's usual maintenance dose of oral corticosteroid. 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.
- 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.
- 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 Short-acting β2 agonist (SABA) use on \>2 days
- ≥1 nocturnal awakening due to asthma
- Pre-bronchodilator (Pre-BD) FEV1 of \<80% predicted (\<90% predicted for patients aged 12 to 17 years) at Visit 2.
- ACQ-6 score \> = 1.5 at Visit 2.
You may not qualify if:
- Known history of clinically important pulmonary disease other than asthma (e.g., active lung infection, chronic obstructive pulmonary disease (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 (e.g,. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome).
- Known history of 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.
- 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.
- 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.
- Current smokers or former smokers with a smoking history of \> 10 pack-years.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (79)
Research Site
Baotou, 14010, China
Research Site
Beijing, 100020, China
Research Site
Beijing, 100034, China
Research Site
Beijing, 100037, China
Research Site
Beijing, 100050, China
Research Site
Beijing, 100730, China
Research Site
Changsha, 410004, China
Research Site
Changsha, 410015, China
Research Site
Changzhi, 46000, China
Research Site
Chengdu, 610041, China
Research Site
Chengdu, 611130, China
Research Site
Chongqing, 400038, China
Research Site
Foshan, 528000, China
Research Site
Ganzhou, 341000, China
Research Site
Guangzhou, 510080, China
Research Site
Guangzhou, 510120, China
Research Site
Guangzhou, 510150, China
Research Site
Guangzhou, 510180, China
Research Site
Guiyang, 550004, China
Research Site
Haikou, 570311, China
Research Site
Hangzhou, 310003, China
Research Site
Hangzhou, 310006, China
Research Site
Hangzhou, 310009, China
Research Site
Hangzhou, 310014, China
Research Site
Hohhot, 010017, China
Research Site
Hohhot, 10050, China
Research Site
Jining, 272029, China
Research Site
Kunming, 650032, China
Research Site
Kunming, 650051, China
Research Site
Lishui, 323000, China
Research Site
Nanchang, 330006, China
Research Site
Nanjing, 2100008, China
Research Site
Nanjing, 210009, China
Research Site
Nanjing, 210029, China
Research Site
Neijiang, 641000, China
Research Site
Qingdao, 110016, China
Research Site
Qingdao, 266000, China
Research Site
Shanghai, 200025, China
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Shanghai, 200032, China
Research Site
Shanghai, 200072, China
Research Site
Shanghai, 200433, China
Research Site
Shanghai, 201199, China
Research Site
Shenyang, 110001, China
Research Site
Shenyang, 110015, China
Research Site
Taiyuan, 030001, China
Research Site
Taizhou, 225300, China
Research Site
Wanzhou, 404000, China
Research Site
Wuhan, 430030, China
Research Site
Xiangtan, 411100, China
Research Site
Xinxiang, 453002, China
Research Site
Xuzhou, 221006, China
Research Site
Xuzhou, 221009, China
Research Site
Yangzhou, 225001, China
Research Site
Yinchuan, 750001, China
Research Site
Yinchuan, 750004, China
Research Site
Zhanjiang, 524001, China
Research Site
Zhuhai, 519099, China
Research Site
Zunyi, 563100, China
Research Site
Iloilo City, 5000, Philippines
Research Site
Manila, 1000, Philippines
Research Site
Bucheon-si, 14584, South Korea
Research Site
Busan, 49241, South Korea
Research Site
Cheonan, 330-715, South Korea
Research Site
Daejeon, 35365, South Korea
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Gwangju, 61469, South Korea
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Seongnam-si, 13620, South Korea
Research Site
Seoul, 03181, South Korea
Research Site
Seoul, 03312, South Korea
Research Site
Seoul, 03722, South Korea
Research Site
Seoul, 04763, South Korea
Research Site
Seoul, 05505, South Korea
Research Site
Seoul, 08308, South Korea
Research Site
Suwon, 16499, South Korea
Research Site
Uijeongbu-si, 11765, South Korea
Research Site
Wŏnju, 26426, South Korea
Research Site
Taipei, 100, Taiwan
Research Site
Taipei, 112, Taiwan
Research Site
Taipei, 114, Taiwan
Research Site
Taoyuan, 333, Taiwan
Related Publications (1)
Jin Y, Guiastrennec B, Stuke M, Yao Y, Zhang Y, Barker P, Jison M, Penland RC, Ding J, Lukka PB. Population Pharmacokinetics and Exposure-Response Analysis of Benralizumab in Chinese Adults, Adolescents, and Pediatric Participants with Severe Eosinophilic Asthma. Clin Pharmacokinet. 2025 Aug;64(8):1231-1243. doi: 10.1007/s40262-025-01538-9. Epub 2025 Jun 23.
PMID: 40551003DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Head
- Organization
- AstraZeneca
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
May 19, 2017
First Posted
June 14, 2017
Study Start
September 7, 2017
Primary Completion
January 30, 2023
Study Completion
January 30, 2023
Last Updated
April 24, 2024
Results First Posted
April 24, 2024
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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 rerefer 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.
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.