NCT03953300进行中（未招募）4 期
A Phase 4, Multicenter, Randomized, Double-blind, Parallel Group, Placebo Controlled Study to Evaluate the Effect of Benralizumab on Structural and Lung Function Changes in Severe Eosinophilic Asthmatics
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 75
- 试验地点
- 35
- 主要终点
- The change in eosinophil numbers expressed as number/mm2 in submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies
研究概览
简要总结
The purpose of the study is to evaluate effect of benralizumab on structural and lung function changes in severe eosinophilic asthmatics.
Changes will be assessed over 48 week treatment period in patients with persistent symptoms despite standard therapy of inhaled corticosteroids (ICS) plus long acting B2-agonist (LABA) with or without additional controller medication.
Patients who complete treatment will enter 4 weeks follow-up period.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18 through 70 years.
- •Physician-diagnosed asthma requiring continuous treatment with medium- or high-dose ICS plus LABA with or without additional controller medication for at least 12 months prior to Visit 1, and current treatment with high-dose ICS plus LABA for at least 3 months prior to Visit 1 with or without additional asthma maintenance medication.
- •Morning pre-BD FEV1 ≥50 to <80% of predicted normal value (PNV) and ≥1 liter (L) or morning pre-BD FEV1 ≥ 50 to < 90% of PNV, if historical pre-BD FEV1 value (within 12 months prior to screening visit) was < 80% of PNV.
- •A blood eosinophil count meeting any of 3 criteria: ≥300 cells/µL during screening or ≥ 220 to < 300 cells/μL during screening and documented eosinophil count of ≥ 300 cells/μL in the past 12 months, or ≥150 to <300 cells/µL during screening plus one of the following: presence of nasal polyps or pre-BD FVC <65% predicted at Visit 2
- •Negative pregnancy test.
- •Asthma control questionnaire (ACQ-6) >1.
- •Fewer than 12 exacerbations within the 6 months prior to Visit 3.
排除标准
- •Any disease or concomitant medication which could affect study results or safety of study participants, including:
- •current smokers
- •history of cancer
- •life-threatening asthma
- •clinically important pulmonary disease other than asthma
- •Use of chronic immunosuppressive medication or receipt of immunoglobulin (or blood products) within 30 days prior to the date informed consent is obtained.
- •Previously received:
- •benralizumab
- •live attenuated vaccines 30 days prior to the date of randomization.
- •bronchial thermoplasty in the last 24 months prior to Visit 1
- •any investigational non-biologic within 30 days (or 5 half-lives) prior to the date informed consent is obtained, whichever is longer.
- •any marketed or investigational biologic for the treatment of asthma within 4 months (or 5 half-lives) prior to the date informed consent is obtained, whichever is longer.
- •Currently pregnant, breastfeeding or lactating women.
研究组 & 干预措施
Benralizumab
Experimental
Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks
干预措施: Benralizumab (Biological)
Placebo
Placebo Comparator
Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks
干预措施: Placebo (Biological)
结局指标
主要结局
The change in eosinophil numbers expressed as number/mm2 in submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies
时间窗: From baseline to Week 48 (Visit 10)
The change in eosinophil numbers expressed as number/mm2 in submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies
The change in airway wall area percentage as the overall median for airway generations 3 and 4 combined as measured by quantitative computed tomography (QCT) imaging
时间窗: From baseline to Week 48 (Visit 10)
The change in airway wall area percentage as the overall median for airway generations 3 and 4 combined as measured by quantitative computed tomography (QCT) imaging
次要结局
- Absolute change in air trapping of the lung with expiratory density less than -856 Hounsfield Units (HU), and as expiratory-to-inspiratory ratio of mean lung density on computed tomography (CT) scans(From baseline to Week 48 (Visit 10))
- Change in airway lumen volume and airway resistance as measured by quantitative computed tomography (QCT)(From baseline to Week 48 (Visit 10))
- Change in endobronchial biopsies on mucin 5AC, oligomeric mucus/gel-forming (MUC5AC)(From baseline to Week 48 (Visit 10))
- Absolute change in R5-R20 (peripheral airway resistance defined as the difference in resistance between 5 Hz [R5, total respiratory system resistance] and 20 Hz [R20, central resistance]) as measured by airwave oscillometry (AO)(From baseline to Week 48 (Visit 10))
- Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)(From baseline to Week 48 (Visit 10))
- Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)(From baseline to Week 48 (Visit 10))
- The change in eosinophil numbers, expressed as number/mm2 in epithelium as measured by major basic protein (MBP) staining in endobronchial biopsies(From baseline to Week 48 (Visit 10))
- Change in endobronchial biopsies on vascularization of the sub-mucosa(From baseline to Week 48 (Visit 10))
- Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) RV/TLC ratio(From baseline to Week 48 (Visit 10))
- Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)(From baseline to Week 48 (Visit 10))
- Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)(From baseline to Week 48 (Visit 10))
- The change in eosinophil numbers, expressed as number/mm2 in epithelium and submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies(From baseline to Week 48 (Visit 10))
- Change in endobronchial biopsies on airway epithelial cell integrity(From baseline to Week 48 (Visit 10))
- Assessments of peripheral airway resistance measured by AO(From baseline to Week 48 (Visit 10))
- Absolute change in area under the reactance curve (AX) as measured by airwave oscillometry (AO)(From baseline to Week 48 (Visit 10))
- Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)(From baseline to Week 48 (Visit 10))
- Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP residual volume (RV)(From baseline to Week 48 (Visit 10))
- Change in post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) as measured by spirometry(From baseline to Week 48 (Visit 10))
- Change in basophil number (number/mm2) in endobronchial biopsies as measured by immunohistochemistry (IHC)(From baseline to Week 48 (Visit 10))
- Change in endobronchial biopsies on reticular basement membrane (RBM) thickening(From baseline to Week 48 (Visit 10))
- Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)(From baseline to Week 48 (Visit 10))
- Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP RV/TLC ratio(From baseline to Week 48 (Visit 10))
- Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP vital capacity (VC)(From baseline to Week 48 (Visit 10))
- Absolute change in air trapping/small airway obstruction derived from regional matching of the inspiratory/expiratory computed tomography (CT) scans(From baseline to Week 48 (Visit 10))
- Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)(From baseline to Week 48 (Visit 10))
- Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)(From baseline to Week 48 (Visit 10))
- Absolute change from baseline to End of Treatment in mucus score assessed using computed tomography (CT) scans(From baseline to Week 48 (Visit 10))
- Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP functional residual capacity (FRC)(From baseline to Week 48 (Visit 10))
- Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)(From baseline to Week 48 (Visit 10))
- Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) RV/TLC ratio(From baseline to Week 48 (Visit 10))
- Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)(From baseline to Week 48 (Visit 10))
- Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP total lung capacity (TLC)(From baseline to Week 48 (Visit 10))
- Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP inspiratory capacity (IC)(From baseline to Week 48 (Visit 10))
- Change in post-bronchodilator (BD) forced vital capacity (FVC) as measured by spirometry(From baseline to Week 48 (Visit 10))
- Change in post-bronchodilator (BD) FEV1/FVC as measured by spirometry(From baseline to Week 48 (Visit 10))
研究者
研究点 (35)
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