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AsthmaPhase 3NCT03186209

Efficacy and Safety Study of Benralizumab in Patients With Uncontrolled Asthma on Medium to High Dose Inhaled Corticosteroid Plus LABA (MIRACLE)

A Phase 3 study testing Benralizumab in people with Asthma, run by AstraZeneca at 79 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 12 to 75 years
Conditions the study is for
Asthma
What is being tested?
Benralizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
695 participants
Where
79 sitesin 4 countries
Study dates
7 Sep 2017to 30 Jan 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

79 sites in 4 countries.

79 sites in 4 countries

China58 sites

  • Research Site

    Baotou, 14010

  • Research Site

    Beijing, 100020

  • Research Site

    Beijing, 100034

  • Research Site

    Beijing, 100037

  • Research Site

    Beijing, 100050

  • Research Site

    Beijing, 100730

  • Research Site

    Changsha, 410004

  • Research Site

    Changsha, 410015

  • Research Site

    Changzhi, 46000

  • Research Site

    Chengdu, 610041

  • Research Site

    Chengdu, 611130

  • Research Site

    Chongqing, 400038

  • Research Site

    Foshan, 528000

  • Research Site

    Ganzhou, 341000

  • Research Site

    Guangzhou, 510080

  • Research Site

    Guangzhou, 510120

  • Research Site

    Guangzhou, 510150

  • Research Site

    Guangzhou, 510180

  • Research Site

    Guiyang, 550004

  • Research Site

    Haikou, 570311

  • Research Site

    Hangzhou, 310003

  • Research Site

    Hangzhou, 310006

  • Research Site

    Hangzhou, 310009

  • Research Site

    Hangzhou, 310014

  • Research Site

    Hohhot, 010017

  • Research Site

    Hohhot, 10050

  • Research Site

    Jining, 272029

  • Research Site

    Kunming, 650032

  • Research Site

    Kunming, 650051

  • Research Site

    Lishui, 323000

  • Research Site

    Nanchang, 330006

  • Research Site

    Nanjing, 2100008

  • Research Site

    Nanjing, 210009

  • Research Site

    Nanjing, 210029

  • Research Site

    Neijiang, 641000

  • Research Site

    Qingdao, 110016

  • Research Site

    Qingdao, 266000

  • Research Site

    Shanghai, 200025

  • Research Site

    Shanghai, 200032

  • Research Site

    Shanghai, 200072

  • Research Site

    Shanghai, 200433

  • Research Site

    Shanghai, 201199

  • Research Site

    Shenyang, 110001

  • Research Site

    Shenyang, 110015

  • Research Site

    Taiyuan, 030001

  • Research Site

    Taizhou, 225300

  • Research Site

    Wanzhou, 404000

  • Research Site

    Wuhan, 430030

  • Research Site

    Xiangtan, 411100

  • Research Site

    Xinxiang, 453002

  • Research Site

    Xuzhou, 221006

  • Research Site

    Xuzhou, 221009

  • Research Site

    Yangzhou, 225001

  • Research Site

    Yinchuan, 750001

  • Research Site

    Yinchuan, 750004

  • Research Site

    Zhanjiang, 524001

  • Research Site

    Zhuhai, 519099

  • Research Site

    Zunyi, 563100

Other trials in China

South Korea15 sites

  • Research Site

    Bucheon-si, 14584

  • Research Site

    Busan, 49241

  • Research Site

    Cheonan, 330-715

  • Research Site

    Daejeon, 35365

  • Research Site

    Gwangju, 61469

  • Research Site

    Seongnam-si, 13620

  • Research Site

    Seoul, 03181

  • Research Site

    Seoul, 03312

  • Research Site

    Seoul, 03722

  • Research Site

    Seoul, 04763

  • Research Site

    Seoul, 05505

  • Research Site

    Seoul, 08308

  • Research Site

    Suwon, 16499

  • Research Site

    Uijeongbu-si, 11765

  • Research Site

    Wŏnju, 26426

Other trials in South Korea

Taiwan4 sites

  • Research Site

    Taipei, 100

  • Research Site

    Taipei, 112

  • Research Site

    Taipei, 114

  • Research Site

    Taoyuan City, 333

Other trials in Taiwan

Philippines2 sites

  • Research Site

    Iloilo City, 5000

  • Research Site

    Manila, 1000

Other trials in Philippines

About this study

Official title: 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.

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.

Read the detailed description

Approximately 666 patients will be randomised. Patients will be stratified by country/region, age group (adult or adolescent), and peripheral blood eosinophil count at time of Visit 1 (<300 or ≥300 cells/μL).All the patients will be randomised to either placebo or benralizumab (1:1 ratio) for a 48-weeks treatment, every 4 weeks for the first 3 doses and then every 8 weeks thereafter.

Conditions
Asthma
Being tested
Benralizumab, Placebo
Keywords
Asthma,, Bronchial Diseases,, Respiratory Tract Diseases,, Lung Diseases,, Obstructive Lung Diseases
Medical subject headings
Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Lung Diseases, Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BenralizumabBiological

    Benralizumab subcutaneously on study week 0 until study week 40 inclusive.

  • PlaceboBiological

    Placebo subcutaneously on study week 0 until study week 40 inclusive.

Study groups in NCT03186209
Study groupRoleWhat they receive
BenralizumabExperimentalBenralizumab administered subcutaneously
Receives: Biological: Benralizumab
PlaceboPlacebo comparatorPlacebo administered subcutaneously
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: From randomization through Study Week 48

Secondary outcomes (15)

  1. 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

    Change from baseline at Week 48 in Pre-bronchodilator FEV1 (L)

    Measured: From randomization through Study Week 48

  2. 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

    Daytime and nighttime symptoms are reported using a response scale ranging from 0 to 3 where 0 indicates no asthma symptoms. The total asthma symptom score is the sum of the daytime and nighttime scores and ranges from 0 to 6; a decrease in score indicates symptom improvement.

    Measured: From randomization through Study Week 48

  3. 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

    Change from baseline at week 48 in total rescue medication use (number of puffs/day)

    Measured: From randomization through Study Week 48

  4. 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

    Change from baseline at week 48 in morning PEF

    Measured: From randomization through Study Week 48

  5. 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

    Change from baseline at week 48 in evening PEF

    Measured: From randomization through Study Week 48

  6. Change From Baseline at Week 48 in the Proportion of Night Awakening Due to Asthma and Requiring Rescue Medication for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL

    Change from baseline at Week 48 in proportion of night awakening due to asthma and requiring rescue medication

    Measured: From randomization through Study Week 48

  7. Change From Baseline at Week 48 in Asthma Control Questionnaire 6 (ACQ-6) for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL

    ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses.

    Measured: From randomization through Study Week 48

  8. Time to First Asthma Exacerbation for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL

    Time to first asthma exacerbation over 48-week treatment period

    Measured: From randomization through Study Week 48

  9. Number and Percentage of Patients With >=1 Asthma Exacerbations Among Patients Who Were on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL

    Number and percentage of patients with at least one exacerbation over 48-week treatment period

    Measured: From randomization through Study Week 48

  10. Change From Baseline at Week 48 in Total Score of St. George's Respiratory Questionnaire (SGRQ) for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL

    The SGRQ is a 50-item PRO instrument developed to measure the HRQoL of patients with airway diseases. The questionnaire is divided into two parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The total score indicates the impact of disease on overall HRQoL. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible HRQoL and 0 indicates the best possible HRQoL.

    Measured: From randomization through Study Week 48

  11. Annual Asthma Exacerbation Rate Associated With an Emergency Room/Urgent Care Visit or a Hospitalization for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL

    Annual asthma exacerbation rate associated with an emergency room/urgent care visit or a hospitalization over 48-week treatment period

    Measured: From randomization through Study Week 48

  12. Number and Percentages of Asthma Specific Health Care Resource Utilization for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL

    Asthma specific health care resource utilization over 48-week treatment period.

    Measured: From randomization through Study Week 48

  13. The Pharmacokinetics (PK) of Benralizumab as Assessed by Trough Concentration

    PK trough concentrations at each visit

    Measured: week 0, week 24, week 48

  14. The Immunogenicity of Benralizumab as Assessed by the Presence of Anti-drug Antibodies (ADAs)

    Anti-drug antibodies (ADA) responses at baseline and post baseline.

    Measured: Pre-treatment until end of 48-week end of treatment

  15. Percent Change From Baseline at Week 48 in Blood Eosinophil Levels for Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma and Baseline Eosinophils >=300/uL

    Percent change from baseline at Week 48 in blood eosinophil levels

    Measured: From randomization through Study Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2017
  2. Study start7 Sep 2017
  3. Primary completion30 Jan 2023
  4. Study completion30 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
695 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03186209
Sponsor's protocol ID
D3250C00036
Other IDs
2017-000702-38, 2017
Status last verified
Mar 2024
First submitted
19 May 2017
Last updated
24 Apr 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Lai K, Sun D, Dai R, Xu X, Zhao J, Wu T, Ho CN, Werkstrom V, Cohen D, Necander S, Zhong N. Efficacy of benralizumab in reducing cough and/or dyspnea frequency, and improving cough-specific health-related quality of life in patients with severe eosinophilic asthma in Asia. Ther Adv Respir Dis. 2026 Jan-Dec;20:17534666261471304. doi: 10.1177/17534666261471304. Epub 2026 Aug 27.

    PubMed 42661269

  • 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.

    PubMed 40551003

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Benralizumab in people with Asthma, run by AstraZeneca at 79 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 79 sites in China, South Korea, Taiwan, Philippines. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annual Asthma Exacerbation Rate in Patients on Medium to High-dose ICS-LABA With Uncontrolled Asthma for Baseline Eosinophils >=300/uL (time frame: From randomization through Study Week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03186209, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2024.

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