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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
408
Pharmaceutical form: Solution Route of administration: Subcutaneous
Pharmaceutical form: Solution Route of administration: Subcutaneous
Pharmaceutical form: Aerosol, capsules, tablets, oral solution Route of administration: Inhaled, oral
Pharmaceutical form: Nebulized, aerosol Route of administration: Inhaled
Investigational Site Number 840031
Birmingham, Alabama, United States
Investigational Site Number 840002
Gilbert, Arizona, United States
Investigational Site Number 840012
Tucson, Arizona, United States
Investigational Site Number 840001
Rolling Hills Estates, California, United States
Investigational Site Number 840036
Owensboro, Kentucky, United States
Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
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.
Time frame: Baseline to Week 52
Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
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.
Time frame: Baseline to Week 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
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in pre-bronchodilator % predicted FEV1 value up to Week 12 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline % predicted FEV1 value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Week 12
Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 12: Type 2 Inflammatory Asthma Phenotype Population
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Least square (LS) means and standard error (SE) were derived from mixed-effect model with repeated measures (MMRM) model with change from baseline in pre-bronchodilator % predicted FEV1 value up to Week 12 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline % predicted FEV1 value and baseline-by-visit interaction as covariates.
Time frame: 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
ACQ-7-IA had 7 questions, which assessed: frequency of nocturnal awakenings, severity of asthma symptoms in the mornings, limitation of daily activities, shortness of breath due to asthma and wheeze, reliever medication use, and FEV1 (% predicted). Participants recalled their previous week asthma and answered 5 symptom questions on 7-point scale ranging from 0 (no impairment) to 6 (maximum impairment). Total score: mean of scores of all 7 questions; ranging from 0 (totally controlled) to 6 (severely uncontrolled), higher score indicated lower asthma control. LS means and SE were derived from MMRM model with change from baseline in ACQ-7-IA values up to Week 52 as response variable and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-7-IA value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Week 24
Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Type 2 Inflammatory Asthma Phenotype Population
ACQ-7-IA had 7 questions, which assessed: frequency of nocturnal awakenings, severity of asthma symptoms in the mornings, limitation of daily activities due to asthma, shortness of breath due to asthma and wheeze, reliever medication use, and FEV1 (% predicted). Participants recalled their previous week asthma and answered 5 symptom questions on 7-point scale ranging from 0 (no impairment) to 6 (maximum impairment). Total score: mean of scores of all 7 questions; ranging from 0 (totally controlled) to 6 (severely uncontrolled), higher score indicated lower asthma control. LS means and SE were derived from MMRM model with change from baseline in ACQ-7-IA values up to Week 52 as response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-7-IA value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Week 24
Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/second, and reported in ppb. LS means and SE were derived from MMRM model with change from baseline in FeNO up to Week 12 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline ICS level, visit, treatment by-visit interaction, baseline FeNO value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Week 12
Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Type 2 Inflammatory Asthma Phenotype Population
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/second, and reported in ppb. LS means and SE were derived from MMRM model with change from baseline in FeNO up to Week 12 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline ICS level, visit, treatment by-visit interaction, baseline FeNO value and baseline-by-visit interaction as covariates.
Time frame: 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
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in pre-bronchodilator % predicted FEV1 values up to Week 52 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline % predicted FEV1 value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Weeks 2, 4, 8, 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
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in pre-bronchodilator % predicted FEV1 values up to Week 52 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline % predicted FEV1 value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Weeks 2, 4, 8, 24, 36, 52
Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
The time to first severe exacerbation was defined as date of the first severe exacerbation event - randomization date +1. 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 related to asthma symptoms or emergency room visit because of asthma requiring systemic corticosteroid treatment. Kaplan-Meier method was used for analysis.
Time frame: Baseline up to Week 52
Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
The time to first severe exacerbation was defined as date of the first severe exacerbation event - randomization date +1. 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 related to asthma symptoms or emergency room visit because of asthma requiring systemic corticosteroid treatment. Kaplan-Meier method was used for analysis.
Time frame: Baseline up to Week 52
Time to First Loss of Asthma Control (LOAC) Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
Time to first LOAC event was date of first LOAC event - first dose date +1. A LOAC event was defined as deterioration of asthma during 52-week treatment period that resulted in any of the following: \>= 6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS dose \>=4 times than dose at Visit 2 (Week 0); a decrease in ante meridiem (AM)/post meridiem (PM) peak flow of 30% or more on 2 consecutive days of treatment, based on defined stability limit (defined as respective mean AM/PM peak expiratory flow obtained over last 7 days prior to randomization (Day 1); severe exacerbation event. Kaplan-Meier method was used for analysis.
Time frame: 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
Time to first LOAC event was date of first LOAC event - first dose date +1. A LOAC event was defined as deterioration of asthma during 52-week treatment period that resulted in any of the following: \>= 6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS dose \>=4 times than dose at Visit 2 (Week 0); a decrease in AM/PM peak flow of 30% or more on 2 consecutive days of treatment, based on defined stability limit (defined as respective mean AM/PM peak expiratory flow obtained over last 7 days prior to randomization (Day 1); severe exacerbation event. Kaplan-Meier method was used for analysis.
Time frame: 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
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in pre-bronchodilator FEV1 values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, sex, ethnicity, baseline height, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline pre-bronchodilator FEV1 value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 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
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in pre-bronchodilator FEV1 values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, sex, ethnicity, baseline height, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline pre-bronchodilator FEV1 value and baseline-by-visit interaction as covariates.
Time frame: 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: Type 2 Inflammatory Asthma Phenotype Population
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in pre-bronchodilator % predicted FEV1 values up to Week 52 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline % predicted FEV1 value and baseline-by-visit interaction as covariates.
Time frame: 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
FEV1 was the volume of air (in liters) exhaled from the lungs in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in pre-bronchodilator % predicted FEV1 values up to Week 52 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline % predicted FEV1 value and baseline-by-visit interaction as covariates.
Time frame: 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
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for AM PEF was performed in morning prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol reliever medication. Baseline AM PEF was the mean AM measurement recorded for the 7 days prior to the first dose of investigational product. LS means and SE were derived from MMRM model with change from baseline in AM PEF (liters/minute) values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline AM PEF (liters/minute) value and baseline-by-visit interaction as covariates.
Time frame: 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
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PM PEF was performed in evening prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol reliever medication. Baseline PM PEF was the mean PM measurement recorded for the 7 days prior to the first dose of investigational product. LS means and SE were derived from MMRM model with change from baseline in PM PEF (liters/minute) values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline PM PEF (liters/minute) value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
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
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for AM PEF was performed in morning prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol reliever medication. Baseline AM PEF was the mean AM measurement recorded for the 7 days prior to the first dose of investigational product. LS means and SE were derived from MMRM model with change from baseline in AM PEF (liters/minute) values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline AM PEF (liters/minute) value and baseline-by-visit interaction as covariates.
Time frame: 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
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PM PEF was performed in evening prior to taking any salbutamol/albuterol or levosalbutamol/levalbuterol reliever medication. Baseline PM PEF was the mean PM measurement recorded for the 7 days prior to the first dose of investigational product. LS means and SE were derived from MMRM model with change from baseline in PM PEF (liters/minute) values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline PM PEF (liters/minute) value and baseline-by-visit interaction as covariates.
Time frame: 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
FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position, measured in liters. LS means and SE were derived from MMRM model with change from baseline in FVC values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, sex, ethnicity, baseline height, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline FVC value and baseline-by-visit interaction as covariates.
Time frame: 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
FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position, measured in liters. LS means and SE were derived from MMRM model with change from baseline in FVC values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, sex, ethnicity, baseline height, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline FVC value and baseline-by-visit interaction as covariates.
Time frame: 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
FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. LS means and SE were derived from MMRM model with change from baseline in FEF 25-75% values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, sex, ethnicity, baseline height, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline FEF 25-75% value and baseline-by-visit interaction as covariates.
Time frame: 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
FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% was defined as the mean FEF between 25% and 75% of the FVC, where FVC was defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. LS means and SE were derived from MMRM model with change from baseline in FE F25-75% values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, sex, ethnicity, baseline height, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline FEF 25-75% value and baseline-by-visit interaction as covariates.
Time frame: 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
Participants were assessed for post-bronchodilator FEV1 30 minutes after bronchodilator administration (200 to 400 mg \[2 to 4 puffs\] of albuterol/salbutamol or 45 to 90 micrograms \[2 to 4 puffs\] of levalbuterol/levosalbutamol). FEV1 was the volume of air (in liters) exhaled in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in post-bronchodilator FEV1 values up to Week 52 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline post-bronchodilator FEV1 value and baseline-by-visit interaction as covariates.
Time frame: 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
Participants were assessed for post-bronchodilator FEV1 30 minutes after bronchodilator administration (200 to 400 mg \[2 to 4 puffs\] of albuterol/salbutamol or 45 to 90 micrograms \[2 to 4 puffs\] of levalbuterol/levosalbutamol). FEV1 was the volume of air (in liters) exhaled in the first second of a forced expiration as measured by spirometer. LS means and SE were derived from MMRM model with change from baseline in post-bronchodilator FEV1 values up to Week 52 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline post-bronchodilator FEV1 value and baseline-by-visit interaction as covariates.
Time frame: 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
The morning asthma symptom score evaluated participant's overall asthma symptoms experienced during the previous night. It ranged from 0 (no asthma symptoms, slept through the night) to 4 (bad night, awake most of the night because of asthma), where lower scores indicate more mild symptoms and higher scores indicate more severe symptoms. LS means and SE were derived from MMRM model with change from baseline in AM asthma symptom score values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline AM asthma symptom score value and baseline-by-visit interaction as covariates.
Time frame: 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: Type 2 Inflammatory Asthma Phenotype Population
The evening asthma symptom score evaluated participant's overall asthma symptoms experienced during the day. It ranged from 0 (very well, no asthma symptoms) to 4 (asthma very bad, unable to carry out daily activities as usual), where lower scores indicate more mild symptoms and higher scores indicate more severe symptoms. LS means and SE were derived from MMRM model with change from baseline in PM asthma symptom score values up to Week 52 as response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline PM asthma symptom score value and baseline-by-visit interaction as covariates.
Time frame: 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
The morning asthma symptom score evaluated participant's overall asthma symptoms experienced during the previous night. It ranged from 0 (no asthma symptoms, slept through the night) to 4 (bad night, awake most of the night because of asthma), where lower scores indicate more mild symptoms and higher scores indicate more severe symptoms. LS means and SE were derived from MMRM model with change from baseline in AM asthma symptom score values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline AM asthma symptom score value and baseline-by-visit interaction as covariates.
Time frame: 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
The evening asthma symptom score evaluated participant's overall asthma symptoms experienced during the day. It ranged from 0 (very well, no asthma symptoms) to 4 (asthma very bad, unable to carry out daily activities as usual), where lower scores indicate more mild symptoms and higher scores indicate more severe symptoms. LS means and SE were derived from MMRM model with change from baseline in PM asthma symptom score values up to Week 52 as response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline PM asthma symptom score value and baseline-by-visit interaction as covariates.
Time frame: 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
ACQ-5-IA has 5 questions, reflecting top-scoring 5 asthma symptoms: frequency of nocturnal awakenings, severity of asthma symptoms in the mornings, limitation of daily activities, shortness of breath due to asthma and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranging from 0 (no impairment) to 6 (maximum impairment). ACQ-5-IA total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), higher scores indicated lower asthma control. LS means and SE were derived from MMRM model with change from baseline in ACQ-5-IA values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-5-IA value and baseline-by-visit interaction as covariates.
Time frame: 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
ACQ-5-IA has 5 questions, reflecting top-scoring 5 asthma symptoms: frequency of nocturnal awakenings, severity of asthma symptoms in the mornings, limitation of daily activities, shortness of breath due to asthma and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranging from 0 (no impairment) to 6 (maximum impairment). ACQ-5-IA total score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), higher scores indicated lower asthma control. LS means and SE were derived from MMRM model with change from baseline in ACQ-5-IA values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-5-IA value and baseline-by-visit interaction as covariates.
Time frame: 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
ACQ-7-IA had 7 questions, assessed: frequency of nocturnal awakenings, severity of asthma symptoms in the mornings, limitation of daily activities, shortness of breath due to asthma and wheeze, reliever medication use, and FEV1 (% predicted). Participants recalled their previous week asthma and answered 5 symptom questions on 7-point scale ranging from 0 (no impairment) to 6 (maximum impairment). Total score:mean of scores of all 7 questions; ranging from 0 (totally controlled) to 6 (severely uncontrolled), higher score indicated lower asthma control. LS means and SE were derived from MMRM model with change from baseline in ACQ-7-IA values up to Week 52 as response variable and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-7-IA value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Weeks 2, 4, 8,12, 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
ACQ-7-IA had 7 questions, assessed: frequency of nocturnal awakenings, severity of asthma symptoms in the mornings, limitation of daily activities due to asthma, shortness of breath due to asthma and wheeze, reliever medication use, and FEV1 (% predicted). Participants recalled their previous week asthma and answered 5 symptom questions on 7-point scale ranging from 0 (no impairment) to 6 (maximum impairment). Total score: mean of scores of all 7 questions; ranging from 0 (totally controlled) to 6 (severely uncontrolled), higher score indicated lower asthma control. LS means and SE were derived from MMRM model with change from baseline in ACQ-7-IA values up to Week 52 as response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-7-IA value and baseline-by-visit interaction as covariates.
Time frame: 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
Participants might be administered salbutamol/albuterol or levosalbutamol/levalbuterol as reliever medication as needed. Number of reliever medication inhalations were recorded daily in electronic diary/PEF meter. When Nebulizer solutions were used as alternative delivery method, nebulizer dose was converted to number of puffs as per conversion factor: salbutamol/albuterol nebulizer solution (2.5 mg) and levosalbutamol/levalbuterol (1.25 mg) corresponds to 4 puffs. Change From Baseline in number of puffs of reliever medication used per 24 hours at specified weeks was reported. LS means and SE were derived from MMRM model with change from baseline in number of puffs of reliever medication/24 hours values up to Week 52 as response variable and treatment, age, baseline: weight group, region, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, baseline number of puffs of reliever medication/24 hours value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Weeks 2, 4, 8, 12, 24, 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
Participants might be administered salbutamol/albuterol or levosalbutamol/levalbuterol as reliever medication as needed. Number of reliever medication inhalations were recorded daily in electronic diary/PEF meter. When Nebulizer solutions were used as alternative delivery method, nebulizer dose was converted to number of puffs as per conversion factor: salbutamol/albuterol nebulizer solution (2.5 mg) and levosalbutamol/levalbuterol (1.25 mg) corresponds to 4 puffs. Change From Baseline in number of puffs of reliever medication used per 24 hours at specified weeks was reported. LS means and SE were derived from MMRM model with change from baseline in number of puffs of reliever medication/24 hours values up to Week 52 as response variable and treatment, age, baseline: weight group, region, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, baseline number of puffs of reliever medication/24 hours value and baseline-by-visit interaction as covariates.
Time frame: 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: Type 2 Inflammatory Asthma Phenotype Population
Participants recorded every morning the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night. Change from baseline in number of nocturnal awakenings per night at specified weeks was reported. LS means and SE were derived from MMRM model with change from baseline in number of nocturnal awakenings values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline number of nocturnal awakenings value and baseline-by-visit interaction as covariates.
Time frame: 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
Participants recorded every morning the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night. Change from baseline in number of nocturnal awakenings per night at specified weeks was reported. LS means and SE were derived from MMRM model with change from baseline in number of nocturnal awakenings values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline number of nocturnal awakenings value and baseline-by-visit interaction as covariates.
Time frame: 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
PAQLQ(S)-IA, a disease-specific, interviewer-administered QoL questionnaire designed to measure functional impairments that are most important to children \>=7 years with asthma. The PAQLQ(S)-IA comprises of 23 items in 3 domains: symptoms (10 items), activity limitation (5 items) and emotional function (8 items). Each item was scored on a 7-point likert scale (1=maximal impairment to 7=no impairment). 23 items of questionnaire were averaged to produce 1 overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all), higher scores indicated better quality of life. LS means and SE were derived from MMRM model with change from baseline in PAQLQ(S)-IA global score values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline PAQLQ(S)-IA global score value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Weeks 12, 24, 36, 52
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
PAQLQ(S)-IA, a disease-specific, interviewer-administered QoL questionnaire designed to measure functional impairments that are most important to children \>=7 years with asthma. The PAQLQ(S)-IA comprises of 23 items in 3 domains: symptoms (10 items), activity limitation (5 items) and emotional function (8 items). Each item was scored on a 7-point likert scale (1=maximal impairment to 7=no impairment). 23 items of questionnaire were averaged to produce 1 overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all), higher scores indicated better quality of life. LS means and SE were derived from MMRM model with change from baseline in PAQLQ(S)-IA global score values up to Week 52 as the response variable, and treatment, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline PAQLQ(S)-IA global score value and baseline-by-visit interaction as covariates.
Time frame: Baseline, Weeks 12, 24, 36, 52
Healthcare Resource Utilization (HCRU): Number of School and Work Days Missed Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population
The number of days missed from school by the participant and the number of days missed from work by the caregiver of participant due to a LOAC were collected in the electronic-case report form (eCRF). Cumulative number of missed days (school days and work days) up to week 52 were computed and summarized using mean and standard deviation (SD).
Time frame: 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
The number of days missed from school by the participant and the number of days missed from work by the caregiver of participant due to a LOAC were collected in the eCRF. Cumulative number of missed days (school days and work days) up to week 52 were computed and summarized using mean and SD.
Time frame: 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: Type 2 Inflammatory Asthma Phenotype Population
The number of days missed from school for the participant and the missed number of days from work for the caregiver due to a LOAC were collected in the eCRF. The percentage of participants who had at least 5 days (school days and work days) missed due to LOAC over the study period was reported.
Time frame: 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
The number of days missed from school for the participant and the missed number of days from work for the caregiver due to a LOAC were collected in the eCRF. The percentage of participants who had at least 5 days (school days and work days) missed due to LOAC over the study period was reported.
Time frame: Baseline to Week 52
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and did not necessary have to had a causal relationship with treatment.TEAEs were defined as AEs that developed or worsened in grade or became serious during TEAE period which was defined as the period from the time of first dose of study drug to the end of post-treatment period. A serious adverse events (SAE) was any untoward medical occurrence that at any dose resulted in: death; or life-threatening experience; or required inpatient hospitalization or prolongation of existing hospitalization; or resulted in persistent or significant disability/incapacity; or was a congenital anomaly/birth defect or a medically important event. TEAEs included both SAEs and non-SAEs.
Time frame: From Baseline up to Week 64
Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum
Data for this outcome measure was planned to be collected and analyzed separately for dupilumab 100 mg and 200 mg dose and not planned to be collected and analyzed for placebo arm.
Time frame: Baseline, Weeks 6, 12, 24, 52, 64
Percentage of Participants With Treatment Emergent Antidrug Antibodies (ADA) Response
ADA response was categorized as: treatment emergent and treatment boosted response. 1) Treatment emergent was defined as an ADA positive response in the assay post first dose, when baseline results were negative or missing. 2) Treatment boosted was defined as: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive. The criteria for positive was defined as "30 to \> 10,000", where low titer (\< 1,000); moderate (1,000 \<= titer \<= 10,000) and high titer (\> 10,000).
Time frame: From Baseline up to Week 64
Percentage of Participants With Seroconversion
Seroconversion was defined as a post-vaccination titer \>=40 (1/dilution) for those with a pre-vaccination titer \<10 (1/dilution), or a \>= 4-fold increase in post-vaccination titer for those with a pre-vaccination titer \>=10 (1/dilution).
Time frame: From Baseline up to Week 64
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Investigational Site Number 840016
Ann Arbor, Michigan, United States
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St Louis, Missouri, United States
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Lincoln, Nebraska, United States
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