E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Asthma (an illness that causes breathing difficulty) that is not fully controlled, so that episodes of breathing difficulty are still occuring despite the use of other available treatments |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of benralizumab on asthma exacerbations in patients on medium to high-dose ICS-LABA with uncontrolled asthma. |
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E.2.2 | Secondary objectives of the trial |
• To assess the effect of benralizumab on pulmonary function
• To assess the effect of benralizumab on asthma symptoms and other asthma control metrics
• To assess the effect of benralizumab on other parameters associated with asthma exacerbations
• To assess the effect of benralizumab on health-related quality of life
• To assess the effect of benralizumab on emergency room/urgent care visits and hospitalizations due to asthma
• To evaluate the effect of benralizumab on health care resource utilization
• To evaluate the pharmacokinetics and immunogenicity of benralizumab
•To assess the impact of benralizumab on blood eosinophil levels |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria:
• 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 European Union 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 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 (eg, LTRAs, tiotropium, cromone, 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, 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.
• 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 SABA use on >2 days
- ≥1 nocturnal awakening due to asthma |
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E.4 | Principal exclusion criteria |
Exclusion Criteria:
• Clinically important pulmonary disease other than asthma (eg, 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 (eg, 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, 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Annual asthma exacerbation rate, which will be analysed in patients with baseline blood eosinophil counts ≥ 300/μL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
All the below secondary efficacy endpoints will be analysed in patients with baseline blood eosinophil counts ≥ 300/μL:
• Pre-bronchodilator FEV1
• Asthma symptom score (total, daytime,and night time), rescue medication use, home lung function (morning and evening PEF), nights with awakening due to asthma, Asthma Control Questionnaire 6 (ACQ-6)
• Time to first asthma exacerbation and proportion of patients with≥1 asthma exacerbation
• St. George’s Respiratory Questionnaire (SGRQ)
• Annual rate of asthma exacerbations that are associated with an emergency room/urgent care visit or a hospitalization
• Asthma specific resource utilization (eg, unscheduled physician visits, use of other asthma medications)
• PK parameters and Anti-drug antibodies
• Blood eosinophils |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
The immunogenicity of benralizumab as assessed by the presence of anti-drug antibodies (ADAs) |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
China |
Korea, Republic of |
Philippines |
Taiwan |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |