A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Children 6 to <12 Years of Age With Uncontrolled Persistent Asthma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 408
- 试验地点
- 99
- 主要终点
- Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
研究概览
简要总结
Primary Objective:
To evaluate the efficacy of dupilumab in children 6 to less than (<) 12 years of age with uncontrolled persistent asthma.
Secondary Objective:
To evaluate in children 6 to <12 years of age with uncontrolled persistent asthma:
- The safety and tolerability of dupilumab.
- The evaluate the effect of dupilumab in improving participant reported outcomes including health related quality of life.
- The dupilumab systemic exposure and incidence of anti-drug antibodies.
- The evaluate the association between dupilumab treatment and pediatric immune responses to vaccines: any vaccination for tetanus, diphtheria, pertussis and/or seasonal trivalent/quadrivalent influenza vaccine.
详细描述
The total study duration per participant was up to 69 weeks, consisted of a screening period of 3-5 weeks, a randomized treatment period of 52 weeks and a post-treatment 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
- 6 Years 至 11 Years（Child）
- 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
Placebo (for Dupilumab), subcutaneous (SC) injection every 2 weeks (q2w) for 52 weeks in combination with stable-dose background therapy of medium-dose inhaled corticosteroids (ICS) with a second controller medication (i.e., long-acting β2 agonist [LABA], long acting muscarinic antagonist [LAMA], leukotriene receptor antagonist [LTRA] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).
干预措施: Placebo (Drug)
Placebo
Placebo (for Dupilumab), subcutaneous (SC) injection every 2 weeks (q2w) for 52 weeks in combination with stable-dose background therapy of medium-dose inhaled corticosteroids (ICS) with a second controller medication (i.e., long-acting β2 agonist [LABA], long acting muscarinic antagonist [LAMA], leukotriene receptor antagonist [LTRA] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).
干预措施: Asthma Controller Therapies (Drug)
Placebo
Placebo (for Dupilumab), subcutaneous (SC) injection every 2 weeks (q2w) for 52 weeks in combination with stable-dose background therapy of medium-dose inhaled corticosteroids (ICS) with a second controller medication (i.e., long-acting β2 agonist [LABA], long acting muscarinic antagonist [LAMA], leukotriene receptor antagonist [LTRA] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).
干预措施: Asthma Reliever Therapies (Drug)
Dupilumab
Dupilumab 200 milligrams (mg) (in 1.14 milliliters [mL] for >30 kilograms [kg] bodyweight [BW]) or 100 mg (in 0.67 mL for less than or equal to (<=) 30 kg BW), SC injection q2w for 52 weeks in combination with stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).
干预措施: Dupilumab (Drug)
Dupilumab
Dupilumab 200 milligrams (mg) (in 1.14 milliliters [mL] for >30 kilograms [kg] bodyweight [BW]) or 100 mg (in 0.67 mL for less than or equal to (<=) 30 kg BW), SC injection q2w for 52 weeks in combination with stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).
干预措施: Asthma Controller Therapies (Drug)
Dupilumab
Dupilumab 200 milligrams (mg) (in 1.14 milliliters [mL] for >30 kilograms [kg] bodyweight [BW]) or 100 mg (in 0.67 mL for less than or equal to (<=) 30 kg BW), SC injection q2w for 52 weeks in combination with stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).
干预措施: Asthma Reliever Therapies (Drug)
结局指标
主要结局
Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
时间窗: Baseline to Week 52
A severe asthma exacerbation event was defined as a deterioration of asthma during the 52-week treatment period requiring: use of systemic corticosteroids for \>=3 days; and/or hospitalization or emergency room visit because of asthma requiring systemic corticosteroid treatment. Annualized event rate was defined as the total number of severe exacerbation events that occurred during the 52-week treatment period divided by the total number of participant-years followed in the 52-week treatment period.
Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
时间窗: Baseline to Week 52
A severe asthma exacerbation event was defined as a deterioration of asthma during the 52-week treatment period requiring: use of systemic corticosteroids for \>=3 days; and/or hospitalization or emergency room visit because of asthma requiring systemic corticosteroid treatment. Annualized event rate was defined as the total number of severe exacerbation 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
- Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline up to Week 52)
- Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 (FEV1) Second at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Week 12)
- Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Week 24: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Week 24)
- Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 12: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Week 12)
- Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Week 12)
- Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Week 12)
- Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 24, 36 and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 24, 36, 52)
- Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Week 24)
- Change From Baseline in Morning (AM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population(Baseline up to Week 52)
- Time to First Loss of Asthma Control Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline up to Week 52)
- Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 24, 36 and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 24, 36, 52)
- Time to First Loss of Asthma Control (LOAC) Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population(Baseline up to Week 52)
- Percent Change From Baseline in Pre-Bronchodilator Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Percent Change From Baseline in Pre-Bronchodilator Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Evening (PM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Morning (AM) Peak Expiratory Flow (PEF) at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-question Version (ACQ-5-IA) at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Evening (PM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Forced Expiratory Flow 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Weeks 2, 4, 8, 12, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8,12, 36, 52)
- Change From Baseline in Number of Puffs of Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Healthcare Resource Utilization (HCRU): Number of School and Work Days Missed Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population(Baseline to Week 52)
- Healthcare Resource Utilization: Number of School and Work Days Missed Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline to Week 52)
- Healthcare Resource Utilization: Percentage of Participants Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline to Week 52)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From Baseline up to Week 64)
- Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-question Version at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Weeks 2, 4, 8, 12, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8,12, 36, 52)
- Change From Baseline in Number of Puffs of Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Change From Baseline in Pediatric Asthma Quality of Life (QoL) Questionnaire With Standardized Activities-Interviewer Administered (PAQLQ[S] IA) Scores at Weeks 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 12, 24, 36, 52)
- Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population(Baseline, Weeks 2, 4, 8, 12, 24, 36, 52)
- Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum(Baseline, Weeks 6, 12, 24, 52, 64)
- Change From Baseline in Pediatric Asthma Quality of Life Questionnaire With Standardized Activities-Interviewer Administered Scores at Weeks 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population(Baseline, Weeks 12, 24, 36, 52)
- Healthcare Resource Utilization: Percentage of Participants Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population(Baseline to Week 52)
- Percentage of Participants With Treatment Emergent Antidrug Antibodies (ADA) Response(From Baseline up to Week 64)
- Percentage of Participants With Seroconversion(From Baseline up to Week 64)