A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) With Type 2 Inflammation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 939
- 试验地点
- 275
- 主要终点
- Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period
研究概览
简要总结
Primary Objective:
To evaluate the efficacy of dupilumab administered every 2 weeks in patients with moderate-or severe Chronic Obstructive Pulmonary Disease (COPD) as measured by
- Annualized rate of acute moderate and severe COPD exacerbation (AECOPD)
Secondary Objectives:
To evaluate the effect of dupilumab administered every 2 weeks on
- Pre-bronchodilator forced expiratory volume in 1 second (FEV1) over 12 weeks compared to placebo
- Health related quality of life, assessed by the change from baseline to Week 52 in the St. George's Respiratory Questionnaire (SGRQ)
- Pre-bronchodilator FEV1 over 52 weeks compared to placebo
- Lung function assessments
- Moderate and severe COPD exacerbations
- To evaluate safety and tolerability
- To evaluate dupilumab systemic exposure and incidence of anti-drug antibodies (ADA)
详细描述
Approximately 68 weeks including a 4-week screening period, a 52-week treatment period, and 12 weeks of follow-up.
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)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dupilumab
Participants received dupilumab 300 mg administered as SC injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of treatment i.e., at Week 52).
干预措施: Dupilumab SAR231893 (Drug)
Dupilumab
Participants received dupilumab 300 mg administered as SC injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of treatment i.e., at Week 52).
干预措施: Inhaled Corticosteroid (Drug)
Dupilumab
Participants received dupilumab 300 mg administered as SC injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of treatment i.e., at Week 52).
干预措施: Inhaled Long-Acting Beta Agonist (Drug)
Dupilumab
Participants received dupilumab 300 mg administered as SC injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of treatment i.e., at Week 52).
干预措施: Inhaled Long-Acting Muscarinic Antagonist (Drug)
Placebo
Participants received placebo matched to dupilumab 300 mg as subcutaneous (SC) injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, end of treatment [EOT] visit occurred 2 weeks after last administration of treatment i.e., at Week 52).
干预措施: Inhaled Corticosteroid (Drug)
Placebo
Participants received placebo matched to dupilumab 300 mg as subcutaneous (SC) injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, end of treatment [EOT] visit occurred 2 weeks after last administration of treatment i.e., at Week 52).
干预措施: Inhaled Long-Acting Beta Agonist (Drug)
Placebo
Participants received placebo matched to dupilumab 300 mg as subcutaneous (SC) injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, end of treatment [EOT] visit occurred 2 weeks after last administration of treatment i.e., at Week 52).
干预措施: Inhaled Long-Acting Muscarinic Antagonist (Drug)
Placebo
Participants received placebo matched to dupilumab 300 mg as subcutaneous (SC) injections q2w up to a maximum of 52 weeks (last dose administered at Week 50, end of treatment [EOT] visit occurred 2 weeks after last administration of treatment i.e., at Week 52).
干预措施: Placebo (Drug)
结局指标
主要结局
Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 52-Week Treatment Period
时间窗: Baseline (Day 1) to Week 52
Moderate exacerbations were recorded by the Investigator and defined as acute exacerbation of COPD (AECOPD) that required either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations were also recorded by the Investigator and defined as AECOPD requiring hospitalization, or observation for \>24 hours in an emergency department/urgent care facility or resulting in death. For both moderate and severe events to be counted as separate events, they were separated by at least 14 days. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated. Events were adjudicated by independent third party.
次要结局
- Change From Baseline in Pre-BD FEV1 at Week 52 in Subgroup of Participants With Baseline FeNO >=20 Ppb(Baseline (Day 1) to Week 52)
- Change From Baseline in Pre-BD FEV1 at Week 52(Baseline (Day 1) to Week 52)
- Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 12(Baseline (Day 1) to Week 12)
- Change From Baseline in Pre-BD FEV1 at Week 12 in Subgroup of Participants With Baseline Fractional Exhaled Nitric Oxide (FeNO) >=20 Parts Per Billion (Ppb)(Baseline (Day 1) to Week 12)
- Annualized Rate of Severe COPD Exacerbations Over the 52-Week Treatment Period(Baseline (Day 1) to Week 52)
- Change From Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at Week 52(Baseline (Day 1) to Week 52)
- Percentage of Participants With SGRQ Improvement >=4 Points at Week 52(Baseline (Day 1) to Week 52)
- Change From Baseline in Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) RS-Total Score at Week 52(Baseline (Day 1) to Week 52)
- Annualized Rate of Moderate or Severe COPD Exacerbation Over the 52-Week Treatment Period in Subgroup of Participants With Baseline FeNO >=20 Ppb(Baseline (Day 1) to Week 52)
- Change From Baseline in Pre-BD Forced Expiratory Flow at 25 Percent (%) to 75% (FEF 25-75%) of Forced Vital Capacity (FVC) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52(Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36, 44 and 52)
- Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab(Up to Week 52)
- Change From Baseline in Pre-BD FEV1 to Weeks 2, 4, 8, 24, 36 and 44(Baseline (Day 1) to Weeks 2, 4, 8, 24, 36 and 44)
- Change From Baseline in Post-BD FEV1 to Weeks 2, 4, 8, 12, 24, 36 and 52(Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(TEAEs were collected from the time from the first administration of study treatment to the last administration of the study treatment + 98 days, up to 491 days)
- Change From Baseline in Post-BD FEF 25-75% to Weeks 2, 4, 8, 12, 24, 36 and 52(Baseline (Day 1) to Weeks 2, 4, 8, 12, 24, 36 and 52)
- Time to First Moderate or Severe COPD Exacerbation During the 52-Week Treatment Period(Baseline (Day 1) and up to Weeks 12, 24, 36 and 52)