NCT02075255已完成3 期
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3 Efficacy and Safety Study of Benralizumab (MEDI-563) to Reduce Oral Corticosteroid Use in Patients With Uncontrolled Asthma on High Dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Chronic Oral Corticosteroid Therapy (ZONDA)
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 220
- 试验地点
- 88
- 主要终点
- Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control
研究概览
简要总结
The purpose of this trial is to confirm if benralizumab can reduce the use of maintenance OCS in systemic corticosteroid dependent patients with severe refractory asthma with elevated eosinophils.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent prior to any study specific procedures.
- •Female and male aged from 18 to 75 years, inclusively.
- •History of physician-diagnosed asthma requiring treatment with medium dose ICS and LABA.
- •Elevated level of peripheral blood eosinophil
- •Documented treatment with high-dose ICS and LABA for at least 6 months prior to Visit 1
- •Chronic oral corticosteroid therapy for at least 6 continuous months directly preceding Visit
- •Subjects must be on doses equivalent to 7.5 - 40 mg/day of prednisolone/prednisone at Visit 1 and be on a stable dose for at least 2 weeks prior to randomization. Patients must agree to switch to study required prednisone/prednisolone as their oral corticosteroid for the duration of the study.
- •Patients with documented failures of OCS reduction within 6 months prior to Visit 1 will not be required to proceed through the dose optimization phase during run-in.
- •Morning pre-bronchodilator (Pre-BD) FEV1 of <80% predicted
- •Evidence of asthma as documented by either:
- •Airway reversibility (FEV1 ≥12% and 200 mL) demonstrated at Visit 1, Visit 2, or Visit 3 using the Maximum Post-bronchodilator Procedure OR Documented reversibility in the previous 24 months prior to Visit 1 OR Airway hyperresponsiveness (PC20 FEV1 methacholine concentration ≤8mg/mL) documented in the previous 12 months prior to planned date of randomization OR Airflow variability in clinic FEV1 ≥20% between 2 consecutive clinic visits documented in the 12 months prior to the planned date of randomization (FEV1 recorded during an exacerbation should not be considered for this criterion).
- •All patients must have reversibility testing performed before randomization to establish a baseline characteristic.
- •If patients do not demonstrate airway reversibility at either Visit 1 or Visit 2 and this is needed to qualify the patient for randomization, the site should reiterate the need to withhold short- and long-acting bronchodilators prior to Visit 3 in an effort to meet this inclusion criterion.
- •At least 1 documented asthma exacerbation in the previous 12 months prior to the date informed consent is obtained
- •Optimized OCS dose reached at least 2 weeks prior to randomization
- •Additional asthma controller medication must not have been initiated during run in/optimization period (not applicable for management of exacerbations during screening/ run in optimization phase)
- •At least 70% compliance with OCS use
- •At least 70% compliance with usual asthma controller ICS-LABA
- •Minimum 70% (i.e. 10 of 14 days) compliance with asthma daily diary (morning and evening diary)
- •Exclusion criteria:
- •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.
- •Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, 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, hematology, clinical chemistry, or urinalysis during run-in/optimization 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
- •History of life-threatening asthma
- •Asthma control reached at an OCS dose of ≤5mg during run-in/OCS optimization phase
- •Qualifies for 3 consecutive dose reductions at Visits 2-4 and continues to meet OCS dose reduction criteria at Visit 5
- •Receipt of oral corticosteroids, other than prednisone or prednisolone, as the maintenance oral steroid controller for asthma symptoms from Visit 1 and throughout the study.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period
排除标准
- 未提供
研究组 & 干预措施
Benralizumab Arm A
Experimental
Benralizumab administered subcutaneously every 4 weeks
干预措施: Benralizumab (Biological)
Benralizumab Arm B
Experimental
Benralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind.
干预措施: Benralizumab (Biological)
Placebo
Placebo Comparator
Placebo administered subcutaneously every 4 weeks
干预措施: Placebo (Biological)
结局指标
主要结局
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control
时间窗: Week 28
Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}\*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
次要结局
- Time to the First Asthma Exacerbation(The time from randomisation to the date of first asthma exacerbation over 28 weeks)
- The Percentage of Patients With ≥50% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control(Week 28)
- Change From Baseline to Week 28 in Asthma Symptom Scores (Daytime)(Change from baseline at week 28)
- Change From Baseline to Week 28 in Home Lung Function (Evening Peak Expiratory Flow)(Change from baseline at week 28)
- AQLQ(s)+12 Responders (Improvement) at Week 28(Week 28)
- Extent of Exposure(From first dose to Week 24)
- Anti-drug Antibody Response(From baseline to follow-up Week 36)
- Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control(Week 28)
- Number of Days in Hospital Due to Asthma(The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up)
- Change From Baseline to Week 28 in Asthma Symptom Scores (Total)(Change from baseline at week 28)
- Change From Baseline to Week 28 in Home Lung Function (Morning Peak Expiratory Flow)(Change from baseline at week 28)
- Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control for Patients With Baseline Eosinophils >=300/uL(Week 28)
- The Proportion of Eligible Patients With ≥100% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control(Week 28)
- The Proportion of Patients With ≤5.0 mg Reduction on Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control.(Week 28)
- Number and Percentage of Patients With ≥1 Asthma Exacerbation(Immediately following the randomisation through Study Week 28)
- The Annualized Rate of Asthma Exacerbation(The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up)
- The Proportion of Patients With Average Final OCS Dose ≤5.0 mg Daily at Visit 14, While Maintaining Asthma Control(Week 28)
- Time to the First Asthma Exacerbation Requiring Hospitalization or ER Visit(The time from randomisation to the date of first asthma exacerbation associated with hospitalization or ER over 28 weeks.)
- The Annualized Rate of Asthma Exacerbations That Are Associated With an Emergency Room Visit or a Hospitalization(The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up)
- Change From Baseline to Week 28 in Pre-bronchodilator FEV1(Change from baseline at week 28)
- Change From Baseline to Week 28 in Asthma Symptom Scores (Nighttime)(Change from baseline at week 28)
- Change From Baseline to Week 28 in the Proportion of Nights With Awakening Due to Asthma Requiring Rescue Medication(Change from baseline at week 28)
- Change From Baseline to Week 28 in ACQ-6(Change from baseline at week 28)
- ACQ-6 Responders (Improvement) at Week 28(Week 28)
- Change From Baseline to Week 28 in Rescue Medication Use(Change from baseline at week 28)
- Serum Concentration of Benralizumab(Pre-first dose to Week 36)
- Residual Volume(From baseline to Week 28)
- Change From Baseline at Week 28 in AQLQ(S)+12 (Overall)(Change from baseline at week 28)
- Inspiratory Capacity(From baseline to Week 28)
- Percent Change From Baseline in Blood Eosinophil Counts(Change from baseline at Week 28)
- Total Lung Capacity(From baseline to Week 28)
- Vital Capacity(From baseline to Week 28)
- Functional Residual Capacity(From baseline to Week 28)
研究者
研究点 (88)
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