E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Eosinophilic Asthma |
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E.1.1.1 | Medical condition in easily understood language |
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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 assess the ability to reduce Oral Corticosteroid (OCS) dose in adult patients with severe eosinophilic asthma treated with benralizumab 30 mg Subcutaneous (SC) |
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E.2.2 | Secondary objectives of the trial |
1. To assess the sustained reduction of daily OCS dose while not losing asthma control during approximately 6 months after the end of OCS down-titration (maintenance phase) in adult patients with severe eosinophilic asthma treated with benralizumab 30 mg SC
2. To assess the effect of OCS down titration protocol on asthma control in adult patients with severe eosinophilic asthma treated with benralizumab 30 mg SC
3. To assess the effect of OCS down titration protocol on quality of life in adult patients with severe eosinophilic asthma treated with benralizumab 30 mg SC |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PONENTE Long Term Follow-up Sub-study. 17 Oct 2020, V.1.0 Objectives: Observational 1-To observe real-world clinical management of OCS dose 12- to 18-months after completion 2-To observe real-world clinical management in background maintenance asthma regimen during the long term follow up period
Safety 1-To observe shift in AI status in patients who had Complete AI or Partial AI at the end of the PONENTE study 2-To observe asthma exacerbations in adult patients during the long term follow up period 3-To assess the safety and tolerability during the long term follow up period 4-To evaluate corticosteroid toxicity during the long term follow up period |
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E.3 | Principal inclusion criteria |
1. Peripheral blood eosinophil count of ≥150 cells/μL assessed by central lab at Visit 1 or ≥ 300 cells/μL in the past 12 months
2. History of physician diagnosed asthma requiring continuous Treatment with high dose ICS (high-dose ICS is budesonide/fomoterol HFA ≥ 640/18 per day or equivalent , fluticasone propionate DPI > 500/day or equivalent, or authorized generics for these products ) plus LABA for at least 6 months prior to Visit 1. The ICS and LABA can be contained within a combination product or given by separate inhalers. The ICS can also be given via nebulized solution for Inhalation
3. Chronic oral corticosteroid therapy equivalent to a daily dose of at least 5 mg of prednisone, for at least 3 continuous months directly preceding Visit 1.
4. Patient should be on a stable OCS dose for at least 4 weeks prior to Visit 1.
5. Non-smokers, current smokers or former smokers with a smoking history of <20 pack-years at Visit 1 |
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E.4 | Principal exclusion criteria |
1. Clinically important pulmonary disease other than asthma or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts
2. Known history of allergy or reaction to the study drug formulation
3. History of anaphylaxis to any biologic therapy
4. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy
5. Asthma exacerbation requiring use of systemic corticosteroids, or an increase in maintenance dose of OCS, or acute upper/lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to Visit 2 (first benralizumab dose)
6. A history of known immunodeficiency disorder including a history of positive human immunodeficiency virus (HIV) test
7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN) confirmed at Visit 1.
8. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
9. Coincident primary adrenal failure (Addison’s disease) or irreversible secondary hypoadrenalism due to another independent cause (e.g. pituitary tumour or its treatment)
10. Co-existent inflammatory conditions for which chronic OCS doses are part of their maintenance treatment such as Giant Cell Arteritis, Polymyalgia Rheumatica
11. Exclusion from genetic research may be for any of the exclusion criteria specified in the main study or allogeneic bone marrow transplant, Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
2. Patients who achieve 100% reduction or a daily OCS dose of ≤5mg, if reason for no further OCS reduction is Adrenal Insufficiency, that are sustained over at least 4 weeks without worsening of asthma |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Visit 3 to End of OCS Reduction Phase
2. Visit 3 to End of OCS Reduction Phase |
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E.5.2 | Secondary end point(s) |
1. Patients who achieve a daily OCS dose of ≤5 mg that are sustained over at least 4 weeks without worsening of asthma
2. Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose, sustained over at least 4 weeks without worsening of asthma
3. Change from baseline in daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Visit 3 to End of OCS Reduction Phase
2. Visit 3 to End of OCS Reduction Phase
3. Visit 3 to End of OCS Reduction Phase |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | No |
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.8.3 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 83 |
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 |
Brazil |
Canada |
Colombia |
Mexico |
Russian Federation |
Taiwan |
United States |
Belgium |
Denmark |
France |
Germany |
Italy |
Poland |
Spain |
Sweden |
United Kingdom |
Argentina |
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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.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |