NCT03406078已完成3 期
A Multicentre, Randomized, Double-Blind, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SOURCE)
适应症
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 150
- 试验地点
- 61
- 主要终点
- Categorized Percent Reduction From Baseline in the Daily OCS Dose While Not Losing Asthma Control
研究概览
简要总结
Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid Dependent Asthma
详细描述
A Multicentre, Randomized, Double-Blind, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid Dependent Asthma
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)
盲法说明
Double-Blind
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have received a physician-prescribed medium- or high-dose ICS as per GINA guideline for at least 12 months
- •Subjects must have received physician prescribed LABA and high dose ICS (total daily dose >500μg fluticasone propionate dry powder formulation equivalent) for at least 3 months. The ICS and LABA can be parts of a combination product, or given by separate inhalers.
- •Additional maintenance asthma controller medications are allowed according to standard practice of care i.e., leukotriene receptor antagonists (LTRAs), theophylline, long-acting muscarinic antagonists (LAMAs), secondary ICS and cromones. The use of these medications must be documented for at least 3 months
- •Subjects must have received OCS for the treatment of asthma for at least 6 months prior to screening and on a stable dose of between ≥ 7.5 to ≤ 30mg (prednisone or prednisolone equivalent) daily or daily equivalent for at least 1 month. The OCS dose may be administered every other day (or different doses every other day); Average dose over two days = The daily dose.
- •Morning pre-bronchodilator (BD) FEV1 must be < 80% predicted normal
- •Subjects must have evidence of asthma as documented by post-BD (albuterol/salbutatomol) reversibility of FEV1 ≥12% and ≥200 mL (15-30 min after administration of 4 puffs of albuterol/salbutamol), documented either in the previous 12 months
- •Subjects must have a history of at least 1 asthma exacerbation event within 12 months
- •Minimum 10 days compliance with the morning and evening eDiary completion and OCS,ICS,LABA as well as other asthma controller medications as captured in the eDiary during the 14 days prior to randomization
- •Documented physician-diagnosed asthma for at least 12 months
排除标准
- •Any clinically important pulmonary disease other than asthma (e.g. active lung infection, Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome).
- •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 subject throughout the study Influence the findings of the study or the interpretation Impede the subject's ability to complete the entire duration of study
- •History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to visit 1.Subjects who have had other malignancies are eligible provided that curative therapy was completed at least 5 years
- •A helminth parasitic infection diagnosed within 6 months prior to screening that has not been treated with, or has failed to respond to, standard of care therapy.
- •Current smokers or subjects with smoking history ≥ 10 pack-years and subjects using vaping products, including electronic cigarettes. Former smokers with a smoking history of <10 pack years and users of vaping or e-cigarette products must have stopped for at least 6 months prior to visit 1 to be eligible.
- •History of chronic alcohol or drug abuse within 12 months
- •Tuberculosis requiring treatment within the 12 months
- •History of any known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
- •Major surgery within 8 weeks prior to visit 1 or planned surgical procedures requiring general anaesthesia or in-subject status for >1 day during the conduct of the study.
- •Clinically significant asthma exacerbation, in the opinion of the Investigator, including those requiring use of systemic corticosteroids or increase in the maintenance dose of OCS within 30 days
结局指标
主要结局
Categorized Percent Reduction From Baseline in the Daily OCS Dose While Not Losing Asthma Control
时间窗: Baseline to Week 48
Categorized percent reduction from baseline at Week 48. Percent change from baseline is defined as {final dose-baseline dose)/baseline dose}\*100, and the categories of percent change from baseline in daily OCS dose are defined as: ≥90% to ≤100% reduction, ≥75% to \<90% reduction, ≥50% to \<75% reduction, \>0% to \<50% reduction, and, no change or any increase.
次要结局
- Change From Baseline in Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire (WPAI+CIQ) Score(Baseline to Week 48)
- Change From Baseline in Asthma Control Questionnaire 6 (ACQ-6) Score(Baseline to Week 48)
- Change From Baseline in European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) Score(Baseline to Week 48)
- Number of Participants With Asthma Specific Resource Utilizations(Baseline to Week 48)
- Change From Baseline From Total Serum IgE(Baseline to Week 48)
- PK: Serum Trough Concentrations(Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 40, Week 48, Week 60)
- Immunogenicity: Incidence of Anti-drug Antibodies (ADA)(Baseline to Week 60)
- Proportion of Subjects With 100% Reduction From Baseline in Daily OCS Dose at Week 48(Baseline to Week 48)
- Proportion of Subjects With ≥50% Reduction From Baseline in Daily OCS Dose at Week 48(Baseline to Week 48)
- Change From Baseline in Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1)(Baseline to Week 48)
- Proportion of Subjects With Daily OCS Dose ≤5 mg at Week 48(Week 48)
- Change From Baseline in Weekly Mean Daily Asthma Symptom Score Via the Daily Asthma Symptom Diary(Baseline to Week 48)
- Change From Baseline in Weekly Mean Number of Night-time Awakening Due to Asthma(Baseline to Week 48)
- Annualised Asthma Exacerbation Rate (AAER)(Baseline to Week 48)
- Change From Baseline in Weekly Mean Rescue Medication Use(Baseline to Week 48)
- Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(s)+12) Total Score(Baseline to Week 48)
- Change From Baseline in Weekly Mean Home Peak Expiratory Flow (PEF) (Morning and Evening)(Baseline to Week 48)
- Change From Baseline in FENO(Baseline to Week 48)
- Change From Baseline in Peripheral Blood Eosinophils(Baseline to Week 48)
研究者
研究点 (61)
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