A Randomized, Double Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Persistent Asthma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 1,902
- 试验地点
- 389
- 主要终点
- Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 12: ITT Population
研究概览
简要总结
Primary Objective:
To evaluate the efficacy of dupilumab (SAR231893 / REGN668) in participants with persistent asthma.
Secondary Objectives:
- To evaluate the safety and tolerability of dupilumab.
- To evaluate the effect of dupilumab on improving participant-reported outcomes including health-related quality of life.
- To evaluate dupilumab systemic exposure and incidence of anti-drug antibodies.
详细描述
The total duration of study period for each participant is 67 to 69 weeks, including a screening period of 3 to 5 weeks, treatment period of 52 weeks, and 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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, 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
Placebo (for Dupilumab 200 mg) q2w
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection every 2 weeks (q2w) from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Placebo (Drug)
Placebo (for Dupilumab 200 mg) q2w
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection every 2 weeks (q2w) from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Inhaled corticosteroid (ICS) therapy (Drug)
Placebo (for Dupilumab 200 mg) q2w
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection every 2 weeks (q2w) from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Albuterol/Salbutamol (Drug)
Placebo (for Dupilumab 200 mg) q2w
2 subcutaneous injections of matched Placebo (for Dupilumab 200 mg) as a loading dose on Day 1 (Week 0), followed by a single injection every 2 weeks (q2w) from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Levalbuterol/Levosalbutamol (Drug)
Dupilumab 200 mg q2w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Dupilumab (Drug)
Dupilumab 200 mg q2w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Inhaled corticosteroid (ICS) therapy (Drug)
Dupilumab 200 mg q2w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Albuterol/Salbutamol (Drug)
Dupilumab 200 mg q2w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 0), followed by a single 200 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Levalbuterol/Levosalbutamol (Drug)
Placebo (for Dupilumab 300 mg) q2w
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Placebo (Drug)
Placebo (for Dupilumab 300 mg) q2w
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Inhaled corticosteroid (ICS) therapy (Drug)
Placebo (for Dupilumab 300 mg) q2w
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Albuterol/Salbutamol (Drug)
Placebo (for Dupilumab 300 mg) q2w
2 subcutaneous injections of matched Placebo (for Dupilumab 300 mg) as a loading dose on Day 1 (Week 0), followed by a single injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Levalbuterol/Levosalbutamol (Drug)
Dupilumab 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines . Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Dupilumab (Drug)
Dupilumab 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines . Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Inhaled corticosteroid (ICS) therapy (Drug)
Dupilumab 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines . Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Albuterol/Salbutamol (Drug)
Dupilumab 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 0), followed by a single 300 mg injection q2w from Week 2 to Week 50 in combination with stable ICS and up to 2 other controller medicines . Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.
干预措施: Levalbuterol/Levosalbutamol (Drug)
结局指标
主要结局
Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 12: ITT Population
时间窗: Baseline, Week 12
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: Intent-to-Treat (ITT) Population
时间窗: Baseline to Week 52
A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for \>=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.
次要结局
- Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population(Baseline, Week 12)
- Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil <0.3 Giga/L(Baseline to Week 52)
- Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ [S]) Self-Administered Global Score at Week 24: ITT Population(Baseline, Week 24)
- Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.3 Giga/L(Baseline, Week 12)
- Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil >=0.15 Giga/L(Baseline to Week 52)
- Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil >=0.3 Giga/L(Baseline to Week 52)
- Change From Baseline in AQLQ (S) Self- Administered Global Score at Week 24: ITT Population With Baseline Eosinophil >=0.3 Giga/L(Baseline, Week 24)
- Annualized Rate of Severe Exacerbation Events Resulting in Hospitalization or Emergency Room Visit During The 52-Week Treatment Period: ITT Population(Baseline to Week 52)
- Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.15 Giga/L(Baseline, Week 12)
- Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 24, 36, and 52)
- Change From Baseline in Morning (AM)/Evening (PM) Peak Expiratory Flow (PEF) at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.3 Giga/L(Baseline, Week 12)
- Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With High Dose ICS at Baseline(Baseline to Week 52)
- Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.15 Giga/L(Baseline, Week 12)
- Change From Baseline in Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With High Dose ICS at Baseline(Baseline, Week 12)
- Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 24: ITT Population(Baseline, Week 24)
- Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil <0.3 Giga/L(Baseline, Week 12)
- Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With High Dose ICS at Baseline(Baseline, Week 12)
- Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Time to First LOAC Event: Kaplan-Meier Estimates During The 52-Week Treatment Period: ITT Population(Baseline up to Week 52)
- Change From Baseline in AQLQ (S) Self-Administered Global Score at Weeks 12, 36, and 52: ITT Population(Baseline, Weeks 12, 36, and 52)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Weeks 12, 24, 36, and 52: ITT Population(Baseline, Weeks 12, 24, 36, and 52)
- Change From Baseline in 22-Item Sino Nasal Outcome Test (SNOT-22) Score at Weeks 12, 24, 36, and 52: ITT Population With Bilateral Nasal Polyposis/Chronic Rhinosinusitis(Baseline, Weeks 12, 24, 36, and 52)
- Percent Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 24, 36, and 52)
- Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Change From Baseline in Number of Puffs of Daily Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Weeks 12, 24, 36, and 52: ITT Population(Baseline, Weeks 12, 24, 36, and 52)
- Change From Baseline in Standardized Rhinoconjunctivitis Quality Of Life Questionnaire, Ages 12+ (RQLQ[S]+12) Score at Weeks 12, 24, 36, and 52: ITT Population With Comorbid Allergic Rhinitis(Baseline, Weeks 12, 24, 36, and 52)
- Annualized Rate of Loss of Asthma Control (LOAC) Event During The 52-Week Treatment Period: ITT Population(Baseline to Week 52)
- Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During The 52-Week Treatment Period: ITT Population(Baseline up to Week 52)
- Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Change From Baseline in ACQ-5 Score at Weeks 2, 4, 8, 12, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 36, and 52)
- Change From Baseline in Asthma Control Questionnaire 7-item Version (ACQ-7) Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)
- Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, and 52)