E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Asthma is a disease that makes breathing difficult as there is swelling of the air passages resulting in airway narrowing. In severe eosinophilic asthma, this is caused by eosinophils blood cells. |
|
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 |
|
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 describe the change from baseline in airway dynamics at week 13 following treatment with benralizumab, using siVaw (specific airway volume) measurements from trimmed airways. |
|
E.2.2 | Secondary objectives of the trial |
1. To describe the change from baseline (week 0) in airway dynamics at week 13 following treatment with benralizumab, as measured by FRI endpoints and mucus plugs scores, irrespective of patient characteristics. 2. To describe the relationship between airway dynamics and conventional lung function measurements, cross-sectionally at baseline (week 0) and irrespective of patient characteristics. 3. To describe the relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at week 13, after accounting for baseline measurements of conventional lung function. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participants who are diagnosed with asthma with documented reversibility post-bronchodilator or salbutamol either historical or at Visit 0 (V0). - Participants who have documented treatment with ICS and LABA for ≥ 3 months prior to V0 with or without oral corticosteroids and additional asthma controllers. - Participants who have documented peripheral blood eosinophil count ≥ 300 cells/μL at V0, or if Oral Corticosteroids (OCS)-dependent, a documented peripheral blood eosinophil count ≥ 150 cells/μL at V0. - Participants who have had a minimum of 2 exacerbations in the last 12 months prior to V0. - Participants who have pre-bronchodilator Forced Vital Capacity (FVC) < 65% of predicted at V0. - Participants who have pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) < 80% of predicted at V0. - Participants who have stable asthma regimen apart from the use of rescue medication including the use of any other asthma medication for at least 3 months prior to V0. - Participants who can perform acceptable and repeatable spirometry. - Participants who can withhold asthma maintenance medication for at least 12 hours prior to V0, 1 and 4 where spirometry and/or Computed Tomography (CT) scan procedures will be performed except for once-a-day dosage where 24 hours will be required. - Persons capable of becoming pregnant, who have a negative pregnancy test prior to administration of the investigational product (IP) and high-resolution CT scan and must agree to use a highly effective method of birth control (confirmed by the investigator – and consistent with local regulations regarding the methods of contraception for those participating in clinical studies) from randomization throughout the study duration and within 12 weeks after last dose of IP. |
|
E.4 | Principal exclusion criteria |
- Participants who are unstable or who experienced an exacerbation/infection in the 6 weeks before V0. - Participants with acute upper or lower airway infection in the 6 weeks before V0. - Participants diagnosed with clinically important pulmonary disease other than asthma, or participants who have ever been diagnosed with pulmonary or systemic disease, other than asthma that are associated with elevated peripheral eosinophil count. - Receipt of any biologic products for asthma within 4 months or 5 half-lives prior to V0 whichever is longer. - History or current use of chronic (i.e., > 4 weeks) immunosuppressive medication. - History of lung volume reduction surgery, lung resection, thermal bronchoplasty at any time before visit 0 (V0) or on active phase of pulmonary rehabilitation. - Participants with current malignancy or history of malignancy. - History of other clinically significant disease or abnormality. - Participants with positive Hepatitis B, C or HIV. - Participants with: Positive COVID-19 test at V0, COVID-19 disease within 6 weeks before V0 or History of severe COVID-19 disease at any time, defined by the need for Intensive Care Unit stay or Mechanical Ventilation (invasive or non-invasive). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Unadjusted within subject difference in siVaw (specific airway volume) measured at TLC, calculated as the mean percent change from baseline (week 0) at week 13 (± 5 days). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline (week 0) week 13 (± 5 days) |
|
E.5.2 | Secondary end point(s) |
1. Unadjusted within subject difference in iVlung, iVlobe, iVaww, air trapping, iRaw, mucus plugs score, BVX, IAD, ventilation mapping and ventilation/perfusion mapping, comparing baseline (week 0) to week 13 (± 5 days). 2. Correlation between imaging endpoints [FRI endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping and ventilation/perfusion mapping) and mucus plugs score] and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1) at baseline (week 0). Correlation between imaging endpoints [FRI endpoints and mucus plugs score] and pre-bronchodilator forced vital capacity (pre-BD FVC) at baseline (week 0). Scatter plots of FRI endpoints and mucus plugs score versus conventional lung function measures (pre-BD FEV1 and pre-BD FVC) at baseline (week 0). Estimated increases in FRI endpoints and mucus plugs score for every one percent increase in pre-BD FEV1 and pre-BD FVC at baseline (week 0). 3. Correlation between the change from baseline (week 0) in imaging endpoints [FRI endpoints and mucus plugs score] at week 13 and the change from baseline (week 0) in pre-BD FEV1 at week 13 (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FEV1. Correlation between the change from baseline (week 0) in imaging endpoints [FRI endpoints and mucus plugs score] at week 13 and the change from baseline (week 0) in pre-BD FVC at week 13 (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FVC. Scatter plots of changes from baseline (week 0) in FRI endpoints and mucus plugs score at week 13 vs. changes from baseline (week 0) in conventional lung function measures (pre-BD FEV1 and pre-BD FVC) at week 13. Estimated change over time [week 13 vs. baseline (week 0)] in FRI endpoints and mucus plugs score, with and without adjustment for conventional lung function measures (pre-BD FEV1 and pre-BD FVC). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Comparing baseline (week 0) to week 13 (± 5 days) 2. At baseline (week 0) 3. Comparing baseline (week 0) to week 13 (± 5 days) |
|
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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
An interventional single group, open-label, uncontrolled, prospective, multicenter clinical trial. |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
United States |
France |
Spain |
Belgium |
Portugal |
United Kingdom |
|
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
|
The end of the study is defined as the date of the last expected visit/contact of the last participant undergoing the study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |