PONENTE: A Multicenter, Open-label, Phase 3b Efficacy and Safety Study of Benralizumab 30 mg Administered Subcutaneously to Reduce Oral Corticosteroid Use in Adult Patients With Severe Eosinophilic Asthma on High Dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Chronic Oral Corticosteroid Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 598
- 试验地点
- 145
- 主要终点
- Patients Who Achieve 100% Reduction in Daily OCS Dose
研究概览
简要总结
This is a study designed to evaluate efficacy and safety of Benralizumab in reducing the Oral Corticosteroid (OCS) use in adult patients with severe asthma who are receiving OCS with or without additional asthma controller medications.
详细描述
This is an open-label, multicenter study designed to evaluate efficacy and safety of reducing daily oral corticosteroid (OCS) use after initiation of 30 mg dose of benralizumab administered subcutaneously (SC) in patients with severe eosinophilic asthma receiving high-dose inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) and OCS with or without additional asthma controller(s).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Peripheral blood eosinophil count of ≥150 cells/μL assessed by central lab at Visit 1 or ≥ 300 cells/μL in the past 12 months
- •History of physician diagnosed asthma requiring continuous treatment with high dose ICS (high-dose ICS is budesonide/formoterol 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
- •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.
- •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
- •Patient should be on a stable OCS dose for at least 4 weeks prior to Visit
- •Non-smokers, current smokers or former smokers with a smoking history of < or =20 pack-years at Visit 1
排除标准
- •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
- •Known history of allergy or reaction to the study drug formulation
- •History of anaphylaxis to any biologic therapy
- •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
- •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)
- •A history of known immunodeficiency disorder including history of a positive human immunodeficiency virus (HIV) test
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN) confirmed at Visit
- •Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
- •Coincident primary adrenal failure (Addison's disease) or irreversible secondary hypoadrenalism due to another independent cause (e.g. pituitary tumour or its treatment)
- •Co-existent inflammatory conditions for which chronic OCS doses are part of their maintenance treatment such as Giant Cell Arteritis, Polymyalgia Rheumatica
- •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
- •Current night-shift workers
结局指标
主要结局
Patients Who Achieve 100% Reduction in Daily OCS Dose
时间窗: Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)
Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg
时间窗: Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)
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
次要结局
- Patients Who Achieve a Daily OCS of ≤5mg(Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.))
- Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose(Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.))
- Change From Baseline in Average Daily OCS Dose (mg)(Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.))