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
- 935
- 试验地点
- 334
- 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 or 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 antidrug 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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a physician diagnosis of COPD who met the following criteria at screening:
- •Current or former smokers with a smoking history of ≥10 pack-years.
- •Moderate-to-severe COPD (post-bronchodilator FEV1/ forced vital capacity [FVC] ratio <0.70 and post-bronchodilator FEV1 % predicted >30% and ≤70%).
- •Medical Research Council (MRC) Dyspnea Scale grade ≥
- •Patient-reported history of signs and symptoms of chronic bronchitis (chronic productive cough) for 3 months in the year up to screening in the absence of other known causes of chronic cough.
- •Documented history of high exacerbation risk defined as exacerbation history of ≥2 moderate or ≥1 severe within the year prior to inclusion. At least one exacerbation should have occurred while the participant was taking inhaled corticosteroid (ICS)/long-acting beta agonist (LABA)/long-acting muscarinic antagonist (LAMA) (or LABA/LAMA if ICS is contraindicated). Moderate exacerbations were recorded by the investigator and defined as AECOPD that required either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. One of the two required moderate exacerbations had to require the use of systemic corticosteroids. Severe exacerbations were recorded by the investigator and defined as AECOPD requiring hospitalization or observation > 24 hours in emergency department/urgent care facility.
- •Background triple therapy (ICS + LABA + LAMA) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to Visit 1; Double therapy (LABA + LAMA) allowed if ICS is contraindicated.
- •Evidence of Type 2 inflammation: Participants with blood eosinophils ≥300 cells/microliter at Visit 1.
排除标准
- •COPD diagnosis for less than 12 months prior to randomization.
- •Participants with current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines, or documented history of asthma.
- •Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome etc) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
- •Cor pulmonale, evidence of right cardiac failure.
- •Long-term treatment with oxygen >4.0 L/min OR if a participant requires more than 2.0 L/min in order to maintain oxygen saturation >88%
- •Hypercapnia requiring Bi-level ventilation.
- •AECOPD as defined in inclusion criteria within 4 weeks prior to screening, or during the screening period.
- •Respiratory tract infection within 4 weeks prior to screening, or during the screening period.
- •History of, or planned pneumonectomy or lung volume reduction surgery. Participants who were participating in the acute phase of a pulmonary rehabilitation program, ie, who started rehabilitation <4 weeks prior to screening (Note: participants in the maintenance phase of a rehabilitation program can be included).
- •Diagnosis of α-1 anti-trypsin deficiency.
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Dupilumab
Participants received dupilumab 300 mg subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks
干预措施: Dupilumab SAR231893 (Drug)
Dupilumab
Participants received dupilumab 300 mg subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks
干预措施: Inhaled Corticosteroid (Drug)
Dupilumab
Participants received dupilumab 300 mg subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks
干预措施: Inhaled Long-Acting Beta Agonist (Drug)
Dupilumab
Participants received dupilumab 300 mg subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks
干预措施: Inhaled Long-Acting Muscarinic Antagonist (Drug)
Placebo
Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks
干预措施: Inhaled Corticosteroid (Drug)
Placebo
Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks
干预措施: Inhaled Long-Acting Beta Agonist (Drug)
Placebo
Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks
干预措施: Inhaled Long-Acting Muscarinic Antagonist (Drug)
Placebo
Participants received placebo matched to dupilumab 300 mg SC injection q2w up to 52 weeks
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) event 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 event that required hospitalization or observation for \>24 hours in an emergency department/urgent care facility or resulted 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 events that occurred during the 52-week treatment period divided by the total number of participant-years followed in the 52-week treatment period.
次要结局
- Annualized Rate of Severe Chronic Obstructive Pulmonary Disease Exacerbations Over the 52-week Treatment Period(Baseline (Day 1) to Week 52)
- Change From Baseline in Forced Expiratory Flow (FEF) 25 to 75 Percent (%) to Weeks 2, 4, 8, 12, 24, 36, 44, and 52(Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 44 and 52)
- Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) to Week 12(Baseline (Day 1) and Week 12)
- Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score to Week 52(Baseline (Day 1) and Week 52)
- Percentage of Participants With Saint George's Respiratory Questionnaire Improvement ≥4 Points at Week 52(Baseline (Day 1) and Week 52)
- Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Week 52(Baseline (Day 1) and Week 52)
- Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 24, 36, and 44(Baseline (Day 1) and Weeks 2, 4, 8, 24, 36 and 44)
- Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second to Weeks 2, 4, 8, 12, 24, 36, and 52(Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36 and 52)
- Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease Exacerbation Event During the 52-week Treatment Period(Baseline (Day 1) and up to Weeks 12, 24, 36 and 52)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(From the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days)
- Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology(From the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days)
- Percentage of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry(From the first dose of study treatment (Day 1) up to the last dose of the study treatment + 98 days, up to 506 days)
- Percentage of Participants With Abnormal Results for Urine Protein in Urinalysis(Baseline (Day 1), Weeks 4, 8, 12, 24, 36, 52 and 64)
- Number of Participants With Anti-Drug Antibodies (ADA) to Dupilumab(Up to Week 52)