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

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ClinicalTrials.gov Identifier: NCT03186209
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Asthma Biological: Benralizumab Biological: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 666 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : September 7, 2017
Estimated Primary Completion Date : February 26, 2021
Estimated Study Completion Date : February 26, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Steroids

Arm Intervention/treatment
Experimental: Benralizumab
Benralizumab administered subcutaneously
Biological: Benralizumab
Benralizumab subcutaneously on study week 0 until study week 40 inclusive.

Placebo Comparator: Placebo
Placebo administered subcutaneously
Biological: Placebo
Placebo subcutaneously on study week 0 until study week 40 inclusive.




Primary Outcome Measures :
  1. 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 ]
    annual asthma exacerbation rate over the 48-week treatment period among benralizumab and placebo groups


Secondary Outcome Measures :
  1. 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 ]
  2. Change From Baseline to Week 48 in Asthma Symptom Score [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
  3. 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 ]
    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. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.

  4. Time to First Asthma Exacerbation [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
  5. Proportion of Patients With >=1 Asthma Exacerbations [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
  6. 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 ]
    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 SGRQ yields a total score and three domain scores (symptoms, activity, and impacts). 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. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment.

  7. 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 ]
  8. Number of Participants That Utilized Health Care Resources [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
  9. The pharmacokinetics (PK) of benralizumab as assessed by concentration [ Time Frame: week 0, week 24, week 48 ]
    Mean PK concentrations at each visit

  10. The immunogenicity of benralizumab as assessed by the presence of anti-drug antibodies (ADAs) [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
  11. Assessment of the impact of benralizumab on blood eosinophil levels [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
    Blood eosinophils

  12. Change in Asthma Rescue Medication [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
    Change from baseline to week 48 in number of rescue medication use (average puffs/day)

  13. Home Lung Function Assessment Based on Morning PEF [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
    Change from baseline to week 48 in home lung function morning peak expiratory flow [PEF]

  14. Home Lung Function Assessment Based on Evening PEF [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
    Change from baseline to week 48 in home lung function evening peak expiratory flow [PEF]

  15. Proportion of Night Awakening Due to Asthma [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ]
    Change from baseline to Week 48 in proportion of night awakening due to asthma


Other Outcome Measures:
  1. Number of subjects with Adverse Events or Serious Adverse Events (AEs/SAEs) [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ]
  2. Shift from baseline to maximum post-baseline in standard chemistry lab parameters [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ]
  3. Shift from baseline to minimum post-baseline in standard chemistry lab parameters [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ]
  4. Shift from baseline to maximum post-baseline in standard hematology lab parameters [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ]
  5. Shift from baseline to minimum post-baseline in standard hematology lab parameters [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ]
  6. Shift from normal to abmormal between baseline and post-baseline for urinalysis [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ]
  7. Changes in vital signs at each visit and at endpoint. [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ]
  8. Changes in ECGs at each visit and at endpoint. [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (eg, 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, 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. 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 β2 agonist (SABA) use on >2 days
    • ≥1 nocturnal awakening due to asthma

Exclusion Criteria:

  1. Clinically important pulmonary disease other than asthma (eg, 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 (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. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186209


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 95 Study Locations
Sponsors and Collaborators
AstraZeneca

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03186209     History of Changes
Other Study ID Numbers: D3250C00036
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by AstraZeneca:
Asthma,
Bronchial Diseases,
Respiratory Tract Diseases,
Lung Diseases,
Obstructive Lung Diseases
Additional relevant MeSH terms:
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Benralizumab
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Anti-Asthmatic Agents
Respiratory System Agents