A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate Dupilumab in Patients With Moderate to Severe Uncontrolled Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 776
- 试验地点
- 201
- 主要终点
- Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-ITT) Population
研究概览
简要总结
Primary Objective:
To evaluate the efficacy of different doses and regimens of dupilumab in participants with moderate to severe uncontrolled asthma.
Secondary Objective:
To evaluate different doses and regimens of dupilumab in participants with moderate to severe uncontrolled asthma, with regard to:
- Safety and tolerability
- Dupilumab systemic exposure and anti-drug antibodies
详细描述
Total duration per participant of approximately 43 weeks including a screening period (14-21 days), a randomized treatment period (24 weeks), and a post-treatment period (16 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
- 18 Years 至 —（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 300 mg q2w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol 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 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: ICS/LABA 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 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Salbutamol/albuterol (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 1), followed by a single 300 mg injection q2w from Week 2 to Week 22 added to stable inhaled corticosteroid/ long-acting beta-agonist (ICS/LABA) therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Levosalbutamol/levalbuterol (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 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol 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 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: ICS/LABA 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 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Salbutamol/albuterol (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 1), followed by a single 200 mg injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Levosalbutamol/levalbuterol (Drug)
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Dupilumab (Drug)
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: placebo (Drug)
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: ICS/LABA therapy (Drug)
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Salbutamol/albuterol (Drug)
Dupilumab 300 mg q4w
2 subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 300 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Levosalbutamol/levalbuterol (Drug)
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Dupilumab (Drug)
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: placebo (Drug)
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: ICS/LABA therapy (Drug)
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Salbutamol/albuterol (Drug)
Dupilumab 200 mg q4w
2 subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1 (Week 1) followed by a Placebo alternating with single 200 mg injection of Dupilumab q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Levosalbutamol/levalbuterol (Drug)
Placebo q2w
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: placebo (Drug)
Placebo q2w
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: ICS/LABA therapy (Drug)
Placebo q2w
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Salbutamol/albuterol (Drug)
Placebo q2w
2 subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 (Week 1) followed by a single injection q2w from Week 2 to Week 22 added to stable ICS/LABA therapy. Salbutamol/albuterol or Levosalbutamol/levalbuterol was given as reliever medication.
干预措施: Levosalbutamol/levalbuterol (Drug)
结局指标
主要结局
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12: High Eosinophils -Intent to Treat (HEos-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.
Absolute Change From Baseline in 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.
次要结局
- Annualized Event Rate of LOAC During The Treatment Period: ITT Population(Baseline to Week 24)
- Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: HEos-ITT Population(Baseline, Week 12)
- Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: ITT Population(Baseline up to Week 24)
- Change From Baseline in AQLQ Global Score at Week 12: ITT Population(Baseline, Week 12)
- Percent Change From Baseline in FEV1 at Week 12: HEos-ITT Population(Baseline, Week 12)
- Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: HEos-ITT Population(Baseline up to Week 24)
- Time to First Severe Exacerbation: Kaplan-Meier Estimates at Week 12 and 24: ITT Population(Baseline up to Week 24)
- Annualized Event Rate of Loss of Asthma Control (LOAC) During The Treatment Period: HEos-ITT Population(Baseline to Week 24)
- Change From Baseline in Evening Asthma Symptom Score at Week 12: ITT Population(Baseline, Week 12)
- Annualized Event Rate of Severe Exacerbation During The Treatment Period: HEos-ITT Population(Baseline to Week 24)
- Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 12: HEos-ITT Population(Baseline, Week 12)
- Change From Baseline in Number of Inhalations Per Day of Salbutamol/Albuterol or Levosalbutamol/Levalbuterol at Week 12: ITT Population(Baseline, Week 12)
- Percent Change From Baseline in FEV1 at Week 12: ITT Population(Baseline, Week 12)
- Annualized Event Rate of Severe Exacerbation During The Treatment Period: ITT Population(Baseline to Week 24)
- Time to First LOAC Event: Kaplan-Meier Estimates at Week 12 and Week 24: HEos-ITT Population(Baseline up to Week 24)
- Change From Baseline in Morning Asthma Symptom Score at Week 12: HEos-ITT Population(Baseline, Week 12)
- Change From Baseline in Morning Asthma Symptom Score at Week 12: ITT Population(Baseline, Week 12)
- Change From Baseline in Evening Asthma Symptom Score at Week 12: HEos-ITT Population(Baseline, Week 12)
- Change From Baseline in ACQ-5 Score at Week 12: ITT Population(Baseline, Week 12)
- Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Global Score at Week 12: HEos-ITT Population(Baseline, Week 12)