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

• Register: ClinicalTrials.gov
• Last refreshed on: 20 February 2023
• Main ID: NCT03186209
• Date of registration: 19/05/2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Efficacy and Safety Study of Benralizumab in Patients With Uncontrolled Asthma on Medium to High Dose Inhaled Corticosteroid Plus LABA (MIRACLE)
• Scientific 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 ß2 Agonist in Patients With Uncontrolled Asthma.
• Date of first enrolment: September 7, 2017
• Target sample size: 695
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03186209
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

China, Korea, Republic of, Philippines, Taiwan

Key inclusion & exclusion criteria

Key Inclusion 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
local 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. 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.

4. 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.

5. 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.

6. 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.

7. 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 ß2 agonist (SABA) use on >2 days

- =1 nocturnal awakening due to asthma

8. Pre-bronchodilator (Pre-BD) FEV1 of <80% predicted (<90% predicted for patients aged
12 to 17 years) at Visit 2.

9. ACQ-6 score > = 1.5 at Visit 2.

Exclusion Criteria:

1. 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).

2. 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.

3. 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.

4. 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.

5. Current smokers or former smokers with a smoking history of > 10 pack-years.



Age minimum: 12 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Asthma

Intervention(s)

Biological: Placebo

Biological: Benralizumab

Primary Outcome(s)

Annual asthma exacerbation rate in patients with uncontrolled asthma on medium to high-dose ICS-LABA [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Secondary Outcome(s)

Change From Baseline to Week 48 in Asthma Symptom Score [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Number of Participants That Utilized Health Care Resources [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Proportion of Night Awakening Due to Asthma [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Proportion of Patients With >=1 Asthma Exacerbations [Time Frame: Immediately following the first administration of study drug through Study Week 48]

The immunogenicity of benralizumab as assessed by the presence of anti-drug antibodies (ADAs) [Time Frame: week 0, week 24, week 48]

Change From Baseline to Week 48 in St. George's Respiratory Questionnaire (SGRQ) [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Time to First Asthma Exacerbation [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Annual asthma exacerbation rate associated with an emergency room/urgent care visit or a hospitalization [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Change From Baseline to Week 48 in Asthma Control Questionnaire 6 (ACQ6) [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Home Lung Function Assessment Based on Evening PEF [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Assessment of the impact of benralizumab on blood eosinophil levels [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Home Lung Function Assessment Based on Morning PEF [Time Frame: Immediately following the first administration of study drug through Study Week 48]

Change in Asthma Rescue Medication [Time Frame: Immediately following the first administration of study drug through Study Week 48]

The pharmacokinetics (PK) of benralizumab as assessed by concentration [Time Frame: week 0, week 24, week 48]

Secondary ID(s)

D3250C00036

Source(s) of Monetary Support

Please refer to primary and secondary sponsors