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Completed

NCT Number: NCT01914757

Efficacy and Safety Study of Benralizumab in Adults and Adolescents Inadequately Controlled on Inhaled Corticosteroid Plus Long-acting β2 Agonist

The purpose of this study is to determine whether Benralizumab reduces the exacerbation rate in patients with a history of asthma exacerbations and uncontrolled asthma receiving ICS-LABA with or without oral corticosteroids and additional asthma controllers.

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Key information

Conditions

Asthma Bronchial Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

12 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Provision of informed consent prior to any study specific procedures
  • Female and male aged 12 to 75 years, inclusively, at the time of Visit 1
  • 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 12 months prior to Visit 1.
  • Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers. The ICS and LABA can be parts of a combination product or given by separate inhalers. The ICS dose must be greater than or equal to 500 μg/day fluticasone propionate dry powder formulation or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion.

Exclusion criteria

  • Clinically important pulmonary disease other than asthma (e.g. 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 (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg- Strauss syndrome, hypereosinophilic syndrome)
  • 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 is obtained or during the screening/run-in period
  • Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in 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

Treatment and study plan

Benralizumab

Biological

Benralizumab subcutaneously on study week 0 until study week 52 inclusive.

Placebo

Biological

Placebo subcutaneously on study week 0 until study week 52 inclusive.

Primary outcomes

  1. Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF.

Secondary outcomes

  1. Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF.

  2. Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils >=300/uL

    Time frame: Immediately following the first administration of study drug through Study Week 56.

  3. Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils <300/uL

    Time frame: Immediately following the first administration of study drug through Study Week 56.

  4. Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils >=300/uL

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.

  5. Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils <300/uL

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.

  6. Change in Asthma Rescue Medication Use

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    Change from Baseline to Week 56 in number of Rescue medication use (puffs/day)

  7. Home Lung Function Assessments Based on PEF

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    Change from Baseline to Week 56 in Home lung function (morning and evening Peak expiratory flow [PEF])

  8. Proportion of Nights With Awakening Due to Asthma

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    Change from Baseline to Week 56 on Proportion of Nights with awakening due to asthma

  9. Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    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.

  10. Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    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.

  11. Number of Patients With >=1 Asthma Exacerbation

    Time frame: Immediately following the first administration of study drug through Study Week 56

  12. Time to First Asthma Exacerbation

    Time frame: Immediately following the first administration of study drug through Study Week 56

  13. Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations

    Time frame: Immediately following the first administration of study drug through Study Week 56.

    Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization (adjudicated)

  14. Pharmacokinetics of Benralizumab

    Time frame: Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 60

    Mean PK Concentration at each visit

  15. Immunogenicity of Benralizumab

    Time frame: Pre-treatment until end of follow-up

    Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.

  16. Extent of Exposure

    Time frame: Immediately following the first administration of study drug through Study Week 56

    Extent of exposure is defined as the duration of treatment in days

  17. Mean Change From Baseline to Week 56 in AQLQ(S)+12

    Time frame: Immediately following the first administration of study drug through Study Week 56

    AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). Total or domain score change of >=0.5 are considered clinically meaningful.

  18. Change From Baseline to Week 56 in EQ-5D-5L VAS

    Time frame: Immediately following the first administration of study drug through Study Week 56

    EQ-5D-5L VAS is to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.

  19. Mean Work Productivity Loss Due to Asthma

    Time frame: Immediately following the first administration of study drug through Study Week 56

    WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. This is only applicable to patients who were employed.

  20. Mean Productivity Loss Due to Asthma in Classroom

    Time frame: Immediately following the first administration of study drug through Study Week 56

    WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Classroom productivity loss is derived by sum of percentage of missed classes due to asthma and product of percentage of actual hours attending classes times degree of asthma affecting classroom productivity. Percentage of missed classes due to asthma is calculated by number of hours missed classes due to asthma divided by total number of hours missed classes plus number of hours actually attending classes. This is only applicable for patients who took classes.

  21. Number of Participants That Utilized Health Care Resources

    Time frame: Immediately following the first administration of study drug through Study Week 56

  22. Patient and Clinician Assessment of Response to Treatment

    Time frame: Immediately following the first administration of study drug through Study Week 56

    CGIC (clinician global impression of change), and PGIC (patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using a 7-point rating scale, ranging from 1 (Very much Improved), to 7 (Very much Worse). This endpoint was added after the second protocol amendment, thus not all patients had data to be analyzed.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

A Multicentre, Randomized, Double-blind, Parallel Group, Placebocontrolled, Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Asthmatic Adults and Adolescents Inadequately Controlled on Inhaled Corticosteroid Plus Long-acting β2 Agonist (CALIMA)

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Aug 2, 2013
Registry last updated
Jan 25, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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