A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase III Study to Evaluate the Efficacy and Safety of Tezepelumab in Adult Participants With Moderate to Very Severe Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 990
- 试验地点
- 324
- 主要终点
- Annualised rate of moderate or severe COPD exacerbations
研究概览
简要总结
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
详细描述
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving inhaled maintenance therapy and having had at least 2 moderate, or 1 severe, COPD exacerbations in the 12 months prior to Visit 1. Subjects will receive monthly subcutaneous injection of one of two different doses of tezepelumab, or placebo, with a maximum treatment duration of 76 weeks and a minimum of 52 weeks. The study also includes a off-treatment safety follow-up period of 12 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blinded
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥40 to ≤80 years old
- •COPD diagnosis ≥1 year,
- •Post-BD FEV1 ≥ 20% and ≤ 70% PN, FEV1/FVC <0.70 at screening
- •Triple (ICS+LABA+LAMA) or dual inhaled COPD therapy, if triple therapy is considered not appropriate, ≥3 consecutive months prior to V1
- •≥2 moderate or ≥1 severe COPD exacerbations in the prior year; At least 1 of 2 moderate exacerbations must require the use of systemic corticosteroids. At least one of the previous exacerbations should be confirmed to have occurred while the participant was on triple or dual inhaled maintenance therapy
- •EOS ≥ 150 cells/μL during screening
- •CAT ≥15 at screening
- •Former or current smokers ≥10 pack-years
排除标准
- •Clin. important pulmonary disease or radiological findings suggestive of a respiratory disease other than COPD
- •Asthma, incl. pediatric, or ACOS
- •Any unstable disorder that can impact participants safety or study outcomes
- •Tuberculosis requiring treatment within 12 months prior V2
- •Malignancies current or past
- •Concomitant therapies:
- •Macrolides (less than 6 months)
- •Systemic immuno-suppressive, -modulating medications
- •LTOT >4.0 L/min or O2 saturation <89% despite LTOT
研究组 & 干预措施
Matching Placebo
Matching placebo, SC, Q4W
干预措施: Placebo (Other)
Dose 1 of Tezepelumab
Tezepelumab, SC, Q4W
干预措施: Tezepelumab (Biological)
Dose 2 of Tezepelumab
Tezepelumab, SC, Q4W
干预措施: Tezepelumab (Biological)
结局指标
主要结局
Annualised rate of moderate or severe COPD exacerbations
时间窗: Baseline up to 76 weeks
The annualised moderate or severe COPD exacerbation rate (based on exacerbations reported by the investigator) up to 76 weeks treatment period compared to placebo.
次要结局
- Change from baseline in post-BD FEV1(From baseline to Week 52)
- Change from baseline in pre-dose/pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1)(From baseline to Week 52)
- Change from baseline in the St. George's Respiratory Questionnaire (SGRQ) total score(From baseline over 52 weeks)
- Annualised rate of severe COPD exacerbations(Baseline up to 76 weeks)
- Annualised rate of COPD exacerbations requiring ER visit and/or hospitalisation(Baseline up to 76 Weeks)
- Clinical meaningful improvement in St. George's Respiratory Questionnaire (SGRQ) total score(From baseline over 52 weeks)
- Change from baseline in the COPD assessment Test (CAT) total score(From baseline over 52 weeks)
- Clinical meaningful improvement in COPD Assessment Test (CAT) total score(From baseline over 52 weeks)
- Time to first severe COPD exacerbation(Baseline up to 76 weeks)
- Pharmacokinetics (PK): Serum trough concentrations(Baseline, Week 24, Week 36, Week 52)
- Annualised rate of severe COPD exacerbations(Baseline up to 76 weeks)
- Annualised rate of COPD exacerbations requiring ER visit and/or hospitalisation(Baseline up to 76 Weeks)
- Clinical meaningful improvement in St. George's Respiratory Questionnaire (SGRQ) total score(From baseline over 52 weeks)
- Change from baseline in post-BD FEV1(From baseline to Week 52)
- Change from baseline in pre-dose/pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1)(From baseline to Week 52)
- Change from baseline in the St. George's Respiratory Questionnaire (SGRQ) total score(From baseline over 52 weeks)
- Annualised rate of moderate or severe COPD exacerbations among participants with EOS ≥ 300 cells/µL collected during screening visit.(Baseline up to 76 weeks)
- Change from baseline in the COPD assessment Test (CAT) total score(From baseline over 52 weeks)
- Clinical meaningful improvement in COPD Assessment Test (CAT) total score(From baseline over 52 weeks)
- Time to first moderate or severe COPD exacerbation(Baseline up to 76 weeks)
- Time to first severe COPD exacerbation(Baseline up to 76 weeks)
- Pharmacokinetics (PK): Serum trough concentrations(Baseline, Week 24, Week 36, Week 52)
- Immunogenicity of anti-drug antibodies (ADA)(Baseline, Week 24, Week 36, Week 52)