A Multicentre, Parallel-group, Phase IIb, Randomised, Double-blind, Placebo-controlled, 3-Arm, 24-Week Study to Evaluate the Efficacy and Safety of AZD6793 Tablets in Adult Participants With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (PRESTO)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 987
- 试验地点
- 367
- 主要终点
- Annualised rate of moderate or severe COPD exacerbations
研究概览
简要总结
This Phase IIb dose-ranging study will evaluate the efficacy and safety of 2 different doses of AZD6793 compared with placebo tablets in participants with moderate to very severe chronic obstructive pulmonary disease.
详细描述
A Multicentre, Parallel-group, Phase IIb, Randomised, Double-blind, Placebo-controlled, 3-Arm, 24-Week Study to Evaluate the Efficacy and Safety of AZD6793 Tablets in Adult Participants with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (PRESTO)
Approximately 350 sites globally will participate in this study. Approximately 970 participants will be randomized to AZD6793 or Placebo. Following CSP V.3.0, participants will be randomized in a 1:1:1 ratio of two doses of AZD6793 vs Placebo.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥40 years of age at the time of signing the informed consent.
- •Documented primary diagnosis of COPD for at least 12 months prior to enrolment.
- •Pre-BD FEV1/FVC < 0.7 at Visit 1 and pre- and post-BD FEV1/FVC < 0.7, and post-BD FEV1 ≥ 25% to < 80% of predicted normal at Visit
- •Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations in the 12 months prior to screening.
- •Documented stable regimen of inhaled triple maintenance therapy or inhaled dual maintenance therapy for ≥ 3 months prior to screening.
- •CAT score ≥ 10 at Visit
- •Current or ex-smokers with a cigarette smoking history of ≥ 10 pack-years.
- •Participants who are clinically stable and free from an exacerbation of COPD for 4 weeks prior to Visit 1 and are also exacerbation free for at least 4 weeks (28 days) prior to Visit 3 (randomisation).
- •Negative pregnancy test at Visit 1 and Visit 3 for Women Of Child-Bearing Potential (WOCBP).
排除标准
- •Clinically important pulmonary disease other than COPD (eg, asthma [current diagnosis per GINA or other accepted guidelines], active pulmonary infection, clinically significant bronchiectasis when bronchiectasis is the predominant diagnosis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha-1 antitrypsin deficiency or primary ciliary dyskinesia).
- •Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant's respiratory symptoms.
- •Any unstable disorder, including, but not limited to, CV, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment.
- •Significant left heart failure.
- •Unstable angina, acute coronary syndrome/acute myocardial infarction or coronary intervention with percutaneous coronary intervention/coronary artery bypass graft within 6 months of randomisation, uncontrolled arrhythmia, or cardiomyopathy, clinically significant aortic stenosis, or signs of pulmonary oedema or volume overload.
- •Pulmonary arterial hypertension, either idiopathic or due to connective tissue or thromboembolic disease.
- •History of another underlying condition that predisposes the participant to infections.
- •History of ulcerative colitis, Crohn's disease, or microscopic colitis diagnosed by either a gastroenterologist or by histopathology.
- •Abnormal laboratory findings.
- •Participants with evidence of active liver disease and/or evidence of chronic liver disease.
- •Participants with history of HIV infection or who test positive for HIV.
- •History of lung volume reduction surgery.
- •Current or history of malignancy within 5 years before the screening visit.
研究组 & 干预措施
Dose 2 of AZD6793
Approximately 290 participants will be randomized to receive Dose 2 of AZD6793
干预措施: AZD6793 (Drug)
Matching Placebo
Approximately 290 participants will be randomized to receive Matching Placebo
干预措施: Placebo (Other)
Dose 1 of AZD6793
Approximately 290 participants will be randomized to receive Dose 1 of AZD6793
干预措施: AZD6793 (Drug)
结局指标
主要结局
Annualised rate of moderate or severe COPD exacerbations
时间窗: From baseline up to 24 Weeks
The annualised moderate or severe COPD exacerbation rate (based on exacerbations reported by the investigator) up to 24 Weeks treatment period compared to placebo
Annualised rate of moderate or severe COPD exacerbations
时间窗: From baseline up to 24 Weeks
The annualised moderate or severe COPD exacerbation rate (based on exacerbations reported by the investigator) up to 24 Weeks treatment period compared to placebo
次要结局
- Time to first moderate or severe COPD exacerbation(From baseline up to 24 Weeks)
- Annualised rate of COPD exacerbations associated with emergency room visits, urgent care visits, or hospitalisations(From baseline up to 24 Weeks)
- Time to first moderate or severe COPD exacerbation(From baseline up to 24 Weeks)
- Annualised rate of COPD exacerbations associated with emergency room visits, urgent care visits, or hospitalisations(From baseline up to 24 Weeks)
- Annualised rate of severe COPD exacerbations(From baseline up to 24 Weeks)
- Annualised rate of COPDCompEx events(From baseline up to 24 Weeks)
- Time to first COPDCompEx event(From baseline up to 24 Weeks)
- Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1)(From baseline to Week 12 and Week 24)
- Change from baseline in post-bronchodilator (post-BD) forced expiratory volume in 1 second (FEV1)(From baseline to Week 12 and Week 24)
- Change from baseline in Breathlessness, Cough and Sputum Scale (BCSS) total score(From baseline over 24 Weeks)
- Change from baseline in COPD Assessment Test (CAT) total score(From baseline over 24 Weeks)
- Change from baseline in St George's Respiratory Questionnaire (SGRQ) total and domain scores(From baseline over 24 Weeks)
- Measurement of plasma concentrations of AZD6793 at specific timepoints(From baseline to Week 4, Week 12 and Week 24)