A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) (COURSE)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 337
- 试验地点
- 1
- 主要终点
- Rate of Moderate or Severe COPD Exacerbations in Participants With Moderate to Very Severe COPD.
研究概览
简要总结
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2a Study to Explore 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 2a, 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 triple inhaled maintenance therapy, and having had 2 or more documented COPD exacerbations in the 12 months prior to Visit 1. Approximately, 338 subjects will be randomized globally. Subjects will be stratified by region and prior number of exacerbations (2 vs. 3 or more). Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52 week treatment period. The study also includes a post-treatment 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
- •History of moderate to very severe physician-diagnosed COPD for at least 12 months prior to enrolment with a post-bronchodilator FEV1/FVC<0.70 and a post-bronchodilator FEV1 ≥20% and ≤80% of predicted normal value.
- •History of at least 2 documented moderate to severe COPD exacerbations within 2 to 52 weeks prior to enrollment.
- •CAT score of ≥15 at enrollment and on day of randomization.
- •Documented treatment with triple therapy for COPD (medium or high dose ICS/LABA/LAMA) throughout the year prior to enrollment. The dose of ICS should be stable for 3 months prior to enrollment.
排除标准
- •Clinically important pulmonary disease other than COPD, as judged by the Investigator (including current or historic asthma diagnosis).
- •Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious (including risk factors for pneumonia), endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable.
- •Major surgery within 8 weeks before enrollment.
- •History of clinically significant infection requiring antibiotics or antiviral medication within 14 days before enrollment.
- •Pregnant or breastfeeding.
- •The chest/lungs with pathology that precludes the patient's ability to complete the study
- •The patient has active COVID 19 infection during screening period.
研究组 & 干预措施
Tezepelumab
Tezepelumab, SC, Q4W
干预措施: Tezepelumab (Biological)
Matching Placebo
Matching placebo, SC, Q4W
干预措施: Placebo (Other)
结局指标
主要结局
Rate of Moderate or Severe COPD Exacerbations in Participants With Moderate to Very Severe COPD.
时间窗: From randomisation up to Week 52
A COPD exacerbation was defined as a change in the participant's usual COPD symptoms that is beyond normal day-to-day variation, is acute in onset, lasts 2 or more days, and may warrant a change in regular medication and leads to any of the following: Use of systemic corticosteroids for at least 3 days, use of antibiotics for at least 3 days, an inpatient hospitalisation due to COPD, or results in death. Analysis was done using a negative binomial model with the response variable as the number of COPD exacerbations experienced during the follow-up for exacerbations. The model included covariates of treatment group, region, and number of exacerbations reported at randomisation as recorded in IWRS (2, \>=3). The logarithm of the time at risk (in years) for exacerbation in the study is used as an offset variable.
次要结局
- Time to First Severe COPD Exacerbation(From randomisation up to Week 52)
- Time to First Moderate/Severe COPD Exacerbation(From randomisation up to Week 52)
- Proportion of Participants COPD Exacerbation Free at Week 52(From randomisation up to Week 52)
- Lease Square (LS) Mean Difference in Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52(Baseline and Week 52)
- Serum Concentration of Tezepelumab(Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled)
- Comparison of Annual Severe COPD Exacerbation Rates Over 52 Weeks(From randomisation up to Week 52)
- Proportion of Participants With >=1 Severe COPD Exacerbations Over 52 Weeks(From randomisation up to Week 52)
- Least Square (LS) Mean Difference in Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 (FEV1) at Week 52(Baseline and Week 52)
- Proportion of Participants Achieving a Minimum Clinically Important Difference of 4 Units or More in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52(Baseline and Week 52)
- Least Square (LS) Mean Difference in Change From Baseline in COPD Assessment Tool (CAT) Total Score at Week 52(Baseline and Week 52)
- Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab(Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled)