VOYAGE: Evaluation of Dupilumab in Children With Uncontrolled Asthma

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02948959
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 408
• Locations: 99
• Arms: 2
• Actual Duration (Months): 40.2
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Dupilumab; Drug: Placebo; Drug: Asthma Controller Therapies; Drug: Asthma Reliever Therapies	Phase 3

Detailed Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 408 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 21, 2017
• Actual Primary Completion Date: Aug 26, 2020
• Actual Study Completion Date: Aug 26, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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).	Drug: Placebo; Pharmaceutical form: Solution Route of administration: Subcutaneous; Drug: Asthma Controller Therapies; Pharmaceutical form: Aerosol, capsules, tablets, oral solution Route of administration: Inhaled, oral; Drug: Asthma Reliever Therapies; Pharmaceutical form: Nebulized, aerosol Route of administration: Inhaled
Experimental: 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).	Drug: Dupilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR231893 (REGN668) ; Drug: Asthma Controller Therapies; Pharmaceutical form: Aerosol, capsules, tablets, oral solution Route of administration: Inhaled, oral; Drug: Asthma Reliever Therapies; Pharmaceutical form: Nebulized, aerosol Route of administration: Inhaled

Outcome Measures

Primary Outcome Measures

1. Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population [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.

2. Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population [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.

Secondary Outcome Measures

1. 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]

   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.

2. 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]

   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.

3. 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]

   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.

4. Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Type 2 Inflammatory Asthma Phenotype Population [Baseline, Week 24]

   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.

5. Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population [Baseline, Week 12]

   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.

6. Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Type 2 Inflammatory Asthma Phenotype Population [Baseline, Week 12]

   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.

7. 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]

   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.

8. 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]

   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.

9. 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]

   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.

10. 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]

    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.

11. 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]

    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.

12. 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]

    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.

13. 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]

    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.

14. 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]

    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.

15. 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]

    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.

16. 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]

    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.

17. 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]

    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.

18. 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]

    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.

19. 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]

    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.

20. 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]

    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.

21. 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]

    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.

22. 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]

    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.

23. 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]

    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.

24. 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]

    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.

25. 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]

    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.

26. 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]

    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.

27. 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]

    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.

28. 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]

    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.

29. 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]

    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.

30. 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]

    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.

31. 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]

    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.

32. 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]

    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.

33. 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]

    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.

34. 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]

    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.

35. 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]

    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.

36. 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]

    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.

37. 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]

    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.

38. 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]

    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.

39. 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]

    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.

40. 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]

    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.

41. Healthcare Resource Utilization (HCRU): Number of School and Work Days Missed Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population [Baseline to Week 52]

    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).

42. 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]

    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.

43. 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]

    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.

44. 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]

    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.

45. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [From Baseline up to Week 64]

    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.

46. Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum [Baseline, Weeks 6, 12, 24, 52, 64]

    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.

47. Percentage of Participants With Treatment Emergent Antidrug Antibodies (ADA) Response [From Baseline up to Week 64]

    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).

48. Percentage of Participants With Seroconversion [From Baseline up to Week 64]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

Children 6 to <12 years of age, with a physician diagnosis of persistent asthma for greater than or equal to (>=)12 months prior to screening, based on clinical history and examination, pulmonary function parameters according to Global initiative for asthma (GINA) 2015 Guidelines and the following criteria:

• Existing background therapy of medium-dose ICS with second controller medication (i.e., long-acting β2 agonist , leukotriene receptor antagonist, long acting muscarinic antagonist, or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller, for at least 3 months with a stable dose >=1 month prior to Screening Visit 1.

• Pre-bronchodilator forced expiratory volume in 1 second (FEV1) <=95 percentage (%) of predicted normal or pre bronchodilator FEV1/forced vital capacity ratio <0.85 at Screening and Baseline Visits.

• Reversibility of at least 10% in FEV1 after the administration of 200 to 400 micrograms (mcg; 2 to 4 puff inhalations with metered-dose inhaler [MDI]) of albuterol/salbutamol or 45 to 90 mcg (2 to 4 puffs with MDI) of levalbuterol/levosalbutamol reliever medication before randomization (up to 3 opportunities during the same visit were allowed with a maximum of 12 puffs of reliever medication if tolerated by the participant).

• Must had experienced, within 1 year prior to Screening Visit 1, any of the following events:

• Treatment with a systemic corticosteroid (oral or parenteral), as prescribed by a healthcare professional for worsening asthma at least once or,

• Hospitalization or emergency visit for worsening asthma.

• Evidence of uncontrolled asthma, with at least one of the following criteria during the 4 (±1) weeks Screening Period:

• Asthma Control Questionnaire-Interviewer Administered (ACQ-IA) ACQ-5 score >=1.5 on at least one day of the Screening Period.

• Use of reliever medication (i.e., albuterol/salbutamol or levalbuterol/levosalbutamol), other than as a preventive for exercise induced bronchospasm, on 3 or more days per week, in at least one week during the Screening Period.

• Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening Period.

• Asthma symptoms 3 or more days per week in at least one week during the Screening Period.

Exclusion criteria:

• Participants <6 or >=12 years of age.

• Participants with <16 kg bodyweight.

• Any other chronic lung disease (cystic fibrosis, bronchopulmonary dysplasia, etc.), which may impair lung function.

• A participant with any history of life threatening asthma (ie, extreme exacerbation that requires intubation).

• Co-morbid disease that might interfere with the evaluation of investigational medicinal product.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840031	Birmingham	Alabama	United States	35209
2	Investigational Site Number 840002	Gilbert	Arizona	United States	85234
3	Investigational Site Number 840012	Tucson	Arizona	United States	85724-5030
4	Investigational Site Number 840001	Rolling Hills Estates	California	United States	90274
5	Investigational Site Number 840036	Owensboro	Kentucky	United States	42301
6	Investigational Site Number 840016	Ann Arbor	Michigan	United States	48106
7	Investigational Site Number 840006	Saint Louis	Missouri	United States	63110-1077
8	Investigational Site Number 840022	Lincoln	Nebraska	United States	68505
9	Investigational Site Number 840023	Great Neck	New York	United States	11021
10	Investigational Site Number 840035	New York	New York	United States	00000
11	Investigational Site Number 840013	New York	New York	United States	10032
12	Investigational Site Number 840007	Rochester	New York	United States	14607
13	Investigational Site Number 840004	Charlotte	North Carolina	United States	28277
14	Investigational Site Number 840021	Durham	North Carolina	United States	27710
15	Investigational Site Number 840008	Cincinnati	Ohio	United States	45229
16	Investigational Site Number 840024	Edmond	Oklahoma	United States	73034
17	Investigational Site Number 840003	San Antonio	Texas	United States	78229
18	Investigational Site Number 840018	La Crosse	Wisconsin	United States	54601
19	Investigational Site Number 032004	Buenos Aires		Argentina	B1602DQD
20	Investigational Site Number 032003	Buenos Aires		Argentina	C1121ABE
21	Investigational Site Number 032002	Caba		Argentina	C1122AAK
22	Investigational Site Number 032001	Caba		Argentina	C1414AIF
23	Investigational Site Number 032006	Mendoza		Argentina	5500
24	Investigational Site Number 036001	Campbelltown		Australia	2560
25	Investigational Site Number 036005	North Adelaide		Australia	5006
26	Investigational Site Number 036003	Parkville/Melbourne		Australia	3052
27	Investigational Site Number 036002	South Brisbane		Australia	4101
28	Investigational Site Number 076008	Blumenau		Brazil	89030-100
29	Investigational Site Number 076001	Porto Alegre		Brazil	90020-090
30	Investigational Site Number 076007	Porto Alegre		Brazil	90610-000
31	Investigational Site Number 076003	Sao Paulo		Brazil	02189-010
32	Investigational Site Number 076002	Sao Paulo		Brazil	04037-002
33	Investigational Site Number 076004	Sao Paulo		Brazil	05403-000
34	Investigational Site Number 076006	Sorocaba		Brazil	18040-425
35	Investigational Site Number 124004	Edmonton		Canada	T6G 2B7
36	Investigational Site Number 124002	Hamilton		Canada	L8S1G5
37	Investigational Site Number 124001	Montreal		Canada	H3T 1C5
38	Investigational Site Number 124003	Quebec		Canada	G1V 4W2
39	Investigational Site Number 152003	Santiago		Chile	7560994
40	Investigational Site Number 152005	Santiago		Chile	838-0418
41	Investigational Site Number 152009	Santiago		Chile	8380453
42	Investigational Site Number 152001	Valdivia		Chile
43	Investigational Site Number 152007	Viña Del Mar		Chile	2520024
44	Investigational Site Number 152002	Viña Del Mar		Chile	2520594
45	Investigational Site Number 170004	Antioquia		Colombia	050010
46	Investigational Site Number 170002	Cali		Colombia	760043
47	Investigational Site Number 348006	Budapest		Hungary	1089
48	Investigational Site Number 348002	Gyula		Hungary	5700
49	Investigational Site Number 348012	Mezőkövesd		Hungary	3400
50	Investigational Site Number 348005	Szeged		Hungary	6720
51	Investigational Site Number 348008	Szigetvár		Hungary	7900
52	Investigational Site Number 348001	Székesfehérvár		Hungary	8000
53	Investigational Site Number 348003	Töröbálint		Hungary	2045
54	Investigational Site Number 348007	Zalaegerszeg		Hungary	8900
55	Investigational Site Number 380007	Catania		Italy	95123
56	Investigational Site Number 380003	Firenze		Italy	50139
57	Investigational Site Number 380004	Padova		Italy	35128
58	Investigational Site Number 380005	Roma		Italy	00146
59	Investigational Site Number 380001	Verona		Italy	37126
60	Investigational Site Number 440002	Kaunas		Lithuania	LT-50161
61	Investigational Site Number 440005	Siauliai		Lithuania	LT-76231
62	Investigational Site Number 440003	Utena		Lithuania	LT-28151
63	Investigational Site Number 440001	Vilnius		Lithuania	LT-08406
64	Investigational Site Number 440004	Vilnius		Lithuania	LT-09108
65	Investigational Site Number 484006	Chihuahua		Mexico	31000
66	Investigational Site Number 484004	Chihuahua		Mexico	31200
67	Investigational Site Number 484003	Durango		Mexico	34080
68	Investigational Site Number 484001	Monterrey		Mexico	64460
69	Investigational Site Number 484002	Veracruz		Mexico	91910
70	Investigational Site Number 616001	Lodz		Poland	90-329
71	Investigational Site Number 616002	Poznan		Poland	60-693
72	Investigational Site Number 642001	Bucuresti		Romania	020395
73	Investigational Site Number 643006	Moscow		Russian Federation	119333
74	Investigational Site Number 643004	Perm		Russian Federation	614066
75	Investigational Site Number 643005	Saint Petersburg		Russian Federation	191144
76	Investigational Site Number 643002	Saint Petersburg		Russian Federation	193312
77	Investigational Site Number 643001	Saint-Petersburg		Russian Federation	194100
78	Investigational Site Number 643003	Saint-Petersburg		Russian Federation	196240
79	Investigational Site Number 710004	Cape Town		South Africa	7500
80	Investigational Site Number 710001	Cape Town		South Africa	7700
81	Investigational Site Number 724001	Barcelona		Spain	08035
82	Investigational Site Number 724006	Esplugues De Llobregat		Spain	08950
83	Investigational Site Number 724005	Pozuelo De Alarcón		Spain	28223
84	Investigational Site Number 724002	Santiago De Compostela		Spain	15706
85	Investigational Site Number 724003	Valencia		Spain	46017
86	Investigational Site Number 792005	Adana		Turkey
87	Investigational Site Number 792008	Ankara		Turkey	06500
88	Investigational Site Number 792001	Ankara		Turkey
89	Investigational Site Number 792006	Bursa		Turkey
90	Investigational Site Number 792003	İstanbul		Turkey
91	Investigational Site Number 792004	Istanbul		Turkey
92	Investigational Site Number 804007	Chernivtsi		Ukraine	58023
93	Investigational Site Number 804004	Dnipro		Ukraine	49101
94	Investigational Site Number 804011	Ivano-Frankivsk		Ukraine	76014
95	Investigational Site Number 804005	Kharkiv		Ukraine	61093
96	Investigational Site Number 804008	Kryvyi Rig		Ukraine	50082
97	Investigational Site Number 804001	Kyiv		Ukraine	03115
98	Investigational Site Number 804002	Zaporizhzhya		Ukraine	69063
99	Investigational Site Number 804003	Zaporizhzhya		Ukraine	69076

Sponsors and Collaborators

• Sanofi
• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Oct 18, 2019
• Statistical Analysis Plan - Sep 14, 2020

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02948959
• Other Study ID Numbers: EFC14153; 2016-001607-23; U1111-1179-4851
• First Posted: Oct 31, 2016
• Last Update Posted: Mar 28, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	The study was conducted at 90 active centers in 17 countries. A total of 631 participants were screened between 21 April 2017 and 22 July 2019, of which 408 participants were enrolled and randomized to receive dupilumab or placebo. A total of 223 participants failed screening mainly due to failure to meet inclusion criteria.
Pre-assignment Detail	Randomization was stratified by inhaled corticosteroids (ICS) dose level (medium or high), blood eosinophils count (less than [<] 300 cells per microliter and greater than or equal to [>=] 300 cells per microliter), and region (Latin America, Eastern Europe, and Western countries). Treatment assignment was done by Interactive Voice/Web Response System (2:1 ratio) to receive dupilumab or placebo.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), subcutaneous (SC) injection every 2 weeks (q2w) for 52 weeks in combination with stable-dose background therapy of medium-dose 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).	Dupilumab 200 milligrams (mg) (in 1.14 milliliters [mL] for >30 kilograms (kg) bodyweight [BW]) or 100 mg (in 0.67 mL for <=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).
Period Title: 52 Weeks Treatment Period
STARTED	135	273
Treated	135	270
Safety Population	134	271
Type 2 Inflammatory Asthma Phenotype Population	114	236
Baseline Blood Eosinophils Count >=300 Cells Per Microlitre Population	84	175
COMPLETED	130	248
NOT COMPLETED	5	25
Period Title: 52 Weeks Treatment Period
STARTED	9	31
COMPLETED	4	19
NOT COMPLETED	5	12

Baseline Characteristics

Arm/Group Title	Placebo	Dupilumab	Total
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).	Total of all reporting groups
Overall Participants	135	273	408
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.9 (1.6)	8.9 (1.7)	8.9 (1.6)
Sex: Female, Male (Count of Participants)
Female	48 35.6%	98 35.9%	146 35.8%
Male	87 64.4%	175 64.1%	262 64.2%
Race/Ethnicity, Customized (Count of Participants)
Caucasian/White	118 87.4%	242 88.6%	360 88.2%
Black/of African descent	9 6.7%	11 4%	20 4.9%
Asian/Oriental	0 0%	2 0.7%	2 0.5%
American Indian or Alaska Native	0 0%	1 0.4%	1 0.2%
Other	8 5.9%	17 6.2%	25 6.1%

Outcome Measures

1. Primary Outcome

Title	Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population which included the randomized participants with baseline blood eosinophil count >=300 cells per microliter.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	84	175
Number (95% Confidence Interval) [exacerbations per participant-years]	0.665	0.235

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab
	Comments	Risk ratio and p-value was derived using negative binomial model with total number of events onset from randomization up to Week 52 visit or last contact date (whichever comes earlier) as response variable, with treatment group, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level and number of severe exacerbation events within 1 year prior to study as covariates and log-transformed standardized observation duration as an offset variable.
	Type of Statistical Test	Superiority
	Comments	To control the type-I error rate for the analysis of outcome measure, a hierarchical testing procedure was applied at a 2-sided 5% significant level. Testing was then performed sequentially in the order endpoints were reported. Hierarchical testing sequence continued only if the previous endpoint was statistically significant.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for statistical significance at 5% significant level.
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.353
	Confidence Interval	(2-Sided) 95%; 0.222 to 0.562
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk ratio, also called relative risk compares the risk (rate) of an event among one group with the risk (rate) among another group.

2. Primary Outcome

Title	Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population which included the randomized participants with baseline blood eosinophil count >=150 cells per microliter or baseline FeNO >=20 ppb.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	114	236
Number (95% Confidence Interval) [exacerbations per participant-years]	0.748	0.305

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab
	Comments	Risk ratio and p-value was derived using negative binomial model with total number of events onset from randomization up to Week 52 visit or last contact date (whichever comes earlier) as response variable, with treatment group, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level and number of severe exacerbation events within 1 year prior to study as covariates and log-transformed standardized observation duration as an offset variable.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for statistical significance at 5% significant level.
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.407
	Confidence Interval	(2-Sided) 95%; 0.274 to 0.605
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk ratio, also called relative risk compares the risk (rate) of an event among one group with the risk (rate) among another group.

3. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'Overall number of participants analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	168
Least Squares Mean (Standard Error) [percent predicted FEV1]	4.83 (1.54)	10.15 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab
	Comments	P-value and LS mean difference 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.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
Statistical Test of Hypothesis	p-Value	0.0036
	Comments	Threshold for statistical significance at 5% significant level.
	Method	Mixed-effect model with repeated measure
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	5.32
	Confidence Interval	(2-Sided) 95%; 1.76 to 8.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 12: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	229
Least Squares Mean (Standard Error) [percent predicted FEV1]	5.32 (1.36)	10.53 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab
	Comments	P-value and LS mean difference 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.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
Statistical Test of Hypothesis	p-Value	0.0009
	Comments	Threshold for statistical significance at 5% significant level.
	Method	Mixed-effect model with repeated measure
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	5.21
	Confidence Interval	(2-Sided) 95%; 2.14 to 8.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	166
Least Squares Mean (Standard Error) [score on a scale]	-0.88 (0.09)	-1.34 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab
	Comments	P-value and LS mean difference were derived from MMRM model with change from baseline in ACQ-7-IA up to Week 52 as the response variable, and treatment, age, weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-7-IA and baseline-by-visit interaction as covariates.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for statistical significance at 5% significant level.
	Method	Mixed-effect model with repeated measure
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -0.66 to -0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	227
Least Squares Mean (Standard Error) [score on a scale]	-0.99 (0.07)	-1.32 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab
	Comments	P-value and LS mean difference were derived from MMRM model with change from baseline in ACQ-7-IA up to Week 52 as the response variable, and treatment, age, weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-7-IA and baseline-by-visit interaction as covariates.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	Threshold for statistical significance at 5% significant level.
	Method	Mixed-effect model with repeated measure
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.50 to -0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	165
Least Squares Mean (Standard Error) [parts per billion]	-0.81 (1.69)	-21.40 (1.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab
	Comments	P-value and LS mean difference were derived from MMRM model with change from baseline in FeNO up to Week 12 as the response variable, and treatment, age, weight group, region, baseline eosinophil level, baseline ICS dose level, visit, treatment by-visit interaction, baseline FeNO value and baseline-by-visit interaction as covariates.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for statistical significance at 5% significant level.
	Method	Mixed-effect model with repeated measure
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-20.59
	Confidence Interval	(2-Sided) 95%; -24.60 to -16.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	226
Least Squares Mean (Standard Error) [parts per billion]	-1.13 (1.43)	-18.97 (1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dupilumab
	Comments	P-value and LS mean difference were derived from MMRM model with change from baseline in FeNO up to Week 12 as the response variable, and treatment, age, weight group, region, baseline eosinophil level, baseline ICS dose level, visit, treatment by-visit interaction, baseline FeNO value and baseline-by-visit interaction as covariates.
	Type of Statistical Test	Superiority
	Comments	Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for statistical significance at 5% significant level.
	Method	Mixed-effect model with repeated measure
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-17.84
	Confidence Interval	(2-Sided) 95%; -21.05 to -14.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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. 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	229
Change at Week 2	4.84 (1.29)	8.11 (0.95)
Change at Week 4	3.55 (1.30)	9.97 (0.97)
Change at Week 8	4.27 (1.29)	10.27 (0.96)
Change at Week 24	4.27 (1.40)	10.92 (1.04)
Change at Week 36	6.63 (1.49)	11.46 (1.10)
Change at Week 52	4.36 (1.50)	12.15 (1.10)

10. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	168
Change at Week 2	3.94 (1.51)	7.49 (1.08)
Change at Week 4	2.19 (1.53)	9.09 (1.12)
Change at Week 8	2.48 (1.42)	9.75 (1.04)
Change at Week 24	3.45 (1.63)	11.10 (1.19)
Change at Week 36	6.87 (1.81)	11.47 (1.31)
Change at Week 52	4.08 (1.80)	12.43 (1.30)

11. Secondary Outcome

Title	Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	114	236
Median (95% Confidence Interval) [days]	NA	NA

12. Secondary Outcome

Title	Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	84	175
Median (95% Confidence Interval) [days]	366.0	NA

13. Secondary Outcome

Title	Time to First Loss of Asthma Control (LOAC) Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	114	236
Median (95% Confidence Interval) [days]	63.5	140.0

14. Secondary Outcome

Title	Time to First Loss of Asthma Control Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	84	175
Median (95% Confidence Interval) [days]	47.5	135.0

15. Secondary Outcome

Title	Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	229
Change at Week 2	0.08 (0.03)	0.14 (0.02)
Change at Week 4	0.06 (0.03)	0.18 (0.02)
Change at Week 8	0.09 (0.03)	0.21 (0.02)
Change at Week 12	0.12 (0.03)	0.22 (0.02)
Change at Week 24	0.14 (0.03)	0.27 (0.02)
Change at Week 36	0.23 (0.03)	0.33 (0.02)
Change at Week 52	0.24 (0.03)	0.41 (0.02)

16. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	168
Change at Week 2	0.07 (0.03)	0.13 (0.02)
Change at Week 4	0.04 (0.03)	0.17 (0.02)
Change at Week 8	0.06 (0.03)	0.20 (0.02)
Change at Week 12	0.12 (0.03)	0.22 (0.02)
Change at Week 24	0.13 (0.03)	0.28 (0.03)
Change at Week 36	0.24 (0.04)	0.33 (0.03)
Change at Week 52	0.25 (0.04)	0.42 (0.03)

17. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	229
Change at Week 2	8.07 (2.00)	13.38 (1.47)
Change at Week 4	6.73 (2.10)	16.01 (1.55)
Change at Week 8	7.68 (1.87)	16.33 (1.41)
Change at Week 12	8.87 (2.10)	16.94 (1.56)
Change at Week 24	7.66 (2.12)	17.61 (1.57)
Change at Week 36	10.88 (2.85)	19.19 (2.06)
Change at Week 52	7.92 (2.81)	20.06 (2.03)

18. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population . Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	168
Change at Week 2	7.55 (2.41)	12.76 (1.73)
Change at Week 4	5.81 (2.57)	15.20 (1.87)
Change at Week 8	6.09 (2.10)	16.01 (1.56)
Change at Week 12	9.56 (2.45)	17.14 (1.79)
Change at Week 24	7.44 (2.54)	18.09 (1.85)
Change at Week 36	12.15 (3.67)	19.65 (2.61)
Change at Week 52	8.50 (3.58)	20.97 (2.54)

19. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	228
Change at Week 2	5.57 (2.66)	6.50 (2.00)
Change at Week 4	7.10 (3.31)	12.81 (2.43)
Change at Week 8	7.37 (3.56)	18.05 (2.59)
Change at Week 12	5.37 (3.93)	19.38 (2.85)
Change at Week 24	8.76 (4.53)	23.32 (3.25)
Change at Week 36	17.70 (4.99)	26.77 (3.56)
Change at Week 52	19.88 (5.16)	31.45 (3.69)

20. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	228
Change at Week 2	7.62 (2.94)	10.60 (2.20)
Change at Week 4	6.92 (3.42)	15.23 (2.52)
Change at Week 8	5.52 (3.60)	20.17 (2.64)
Change at Week 12	1.71 (3.92)	19.68 (2.85)
Change at Week 24	3.78 (4.61)	22.75 (3.32)
Change at Week 36	12.55 (5.06)	24.69 (3.62)
Change at Week 52	16.46 (5.20)	28.20 (3.73)

21. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	167
Change at Week 2	5.85 (2.97)	7.94 (2.21)
Change at Week 4	5.62 (3.80)	11.75 (2.76)
Change at Week 8	5.54 (4.09)	17.32 (2.96)
Change at Week 12	4.77 (4.65)	19.25 (3.34)
Change at Week 24	4.78 (5.05)	23.62 (3.61)
Change at Week 36	14.80 (5.77)	26.78 (4.08)
Change at Week 52	19.75 (6.33)	32.80 (4.49)

22. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	167
Change at Week 2	5.64 (3.42)	10.02 (2.53)
Change at Week 4	4.36 (3.96)	13.09 (2.89)
Change at Week 8	0.92 (4.05)	17.51 (2.96)
Change at Week 12	-1.37 (4.57)	17.73 (3.30)
Change at Week 24	-1.37 (5.21)	20.30 (3.74)
Change at Week 36	7.52 (6.01)	23.23 (4.26)
Change at Week 52	14.67 (6.39)	26.60 (4.54)

23. Secondary Outcome

Title	Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	229
Change at Week 2	0.07 (0.02)	0.07 (0.02)
Change at Week 4	0.07 (0.03)	0.11 (0.02)
Change at Week 8	0.10 (0.02)	0.13 (0.02)
Change at Week 12	0.12 (0.03)	0.14 (0.02)
Change at Week 24	0.16 (0.03)	0.20 (0.02)
Change at Week 36	0.22 (0.03)	0.28 (0.02)
Change at Week 52	0.27 (0.03)	0.37 (0.02)

24. Secondary Outcome

Title	Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	168
Change at Week 2	0.07 (0.03)	0.06 (0.02)
Change at Week 4	0.08 (0.03)	0.09 (0.02)
Change at Week 8	0.09 (0.03)	0.13 (0.02)
Change at Week 12	0.13 (0.03)	0.14 (0.02)
Change at Week 24	0.17 (0.03)	0.22 (0.03)
Change at Week 36	0.24 (0.04)	0.28 (0.03)
Change at Week 52	0.29 (0.04)	0.38 (0.03)

25. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	229
Change at Week 2	0.11 (0.05)	0.28 (0.04)
Change at Week 4	0.07 (0.05)	0.34 (0.04)
Change at Week 8	0.10 (0.05)	0.39 (0.04)
Change at Week 12	0.14 (0.05)	0.41 (0.04)
Change at Week 24	0.16 (0.05)	0.44 (0.04)
Change at Week 36	0.29 (0.05)	0.49 (0.04)
Change at Week 52	0.29 (0.06)	0.60 (0.04)

26. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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-dos medication ICS with second controller. 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	168
Change at Week 2	0.07 (0.05)	0.29 (0.04)
Change at Week 4	0.00 (0.05)	0.33 (0.04)
Change at Week 8	0.02 (0.06)	0.40 (0.04)
Change at Week 12	0.10 (0.05)	0.42 (0.04)
Change at Week 24	0.12 (0.06)	0.47 (0.04)
Change at Week 36	0.27 (0.06)	0.51 (0.05)
Change at Week 52	0.26 (0.07)	0.65 (0.05)

27. Secondary Outcome

Title	Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	230
Change at Week 2	0.61 (1.26)	1.51 (0.92)
Change at Week 4	-0.02 (1.15)	2.42 (0.86)
Change at Week 8	-0.79 (1.21)	2.85 (0.90)
Change at Week 12	-0.32 (1.23)	2.48 (0.91)
Change at Week 24	-0.50 (1.31)	2.60 (0.96)
Change at Week 36	0.55 (1.46)	3.15 (1.07)
Change at Week 52	-0.75 (1.48)	3.62 (1.08)

28. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	169
Change at Week 2	0.10 (1.49)	0.52 (1.07)
Change at Week 4	-0.29 (1.35)	1.44 (1.00)
Change at Week 8	-2.05 (1.31)	1.81 (0.98)
Change at Week 12	-0.61 (1.44)	2.28 (1.04)
Change at Week 24	-0.80 (1.54)	2.25 (1.12)
Change at Week 36	0.72 (1.80)	2.87 (1.31)
Change at Week 52	-0.52 (1.79)	3.13 (1.30)

29. Secondary Outcome

Title	Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	228
Change at Week 2	-0.22 (0.04)	-0.18 (0.03)
Change at Week 4	-0.29 (0.05)	-0.34 (0.04)
Change at Week 8	-0.37 (0.05)	-0.39 (0.04)
Change at Week 12	-0.34 (0.05)	-0.48 (0.04)
Change at Week 24	-0.46 (0.05)	-0.56 (0.04)
Change at Week 36	-0.48 (0.05)	-0.56 (0.04)
Change at Week 52	-0.50 (0.05)	-0.61 (0.04)

30. Secondary Outcome

Title	Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	228
Change at Week 2	-0.17 (0.05)	-0.13 (0.03)
Change at Week 4	-0.25 (0.05)	-0.29 (0.04)
Change at Week 8	-0.33 (0.06)	-0.40 (0.04)
Change at Week 12	-0.30 (0.06)	-0.45 (0.04)
Change at Week 24	-0.44 (0.06)	-0.53 (0.04)
Change at Week 36	-0.47 (0.06)	-0.55 (0.04)
Change at Week 52	-0.50 (0.06)	-0.59 (0.04)

31. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	167
Change at Week 2	-0.24 (0.05)	-0.20 (0.04)
Change at Week 4	-0.32 (0.06)	-0.34 (0.04)
Change at Week 8	-0.38 (0.06)	-0.40 (0.05)
Change at Week 12	-0.33 (0.06)	-0.48 (0.04)
Change at Week 24	-0.45 (0.06)	-0.55 (0.04)
Change at Week 36	-0.46 (0.06)	-0.56 (0.04)
Change at Week 52	-0.50 (0.06)	-0.62 (0.04)

32. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	167
Change at Week 2	-0.18 (0.05)	-0.15 (0.04)
Change at Week 4	-0.27 (0.06)	-0.29 (0.04)
Change at Week 8	-0.30 (0.06)	-0.41 (0.05)
Change at Week 12	-0.29 (0.07)	-0.48 (0.05)
Change at Week 24	-0.42 (0.06)	-0.53 (0.05)
Change at Week 36	-0.43 (0.06)	-0.56 (0.05)
Change at Week 52	-0.51 (0.06)	-0.60 (0.04)

33. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	227
Change at Week 2	-0.72 (0.09)	-0.77 (0.06)
Change at Week 4	-0.86 (0.08)	-1.09 (0.06)
Change at Week 8	-1.04 (0.09)	-1.24 (0.07)
Change at Week 12	-1.04 (0.08)	-1.35 (0.06)
Change at Week 24	-1.18 (0.08)	-1.46 (0.06)
Change at Week 36	-1.25 (0.08)	-1.57 (0.06)
Change at Week 52	-1.30 (0.07)	-1.70 (0.05)

34. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	166
Change at Week 2	-0.63 (0.11)	-0.76 (0.08)
Change at Week 4	-0.75 (0.10)	-1.10 (0.07)
Change at Week 8	-0.98 (0.10)	-1.27 (0.07)
Change at Week 12	-1.00 (0.10)	-1.37 (0.07)
Change at Week 24	-1.06 (0.09)	-1.48 (0.07)
Change at Week 36	-1.17 (0.09)	-1.59 (0.07)
Change at Week 52	-1.25 (0.08)	-1.71 (0.06)

35. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	166
Change at Week 2	-0.50 (0.09)	-0.70 (0.07)
Change at Week 4	-0.64 (0.09)	-1.02 (0.06)
Change at Week 8	-0.83 (0.09)	-1.16 (0.06)
Change at Week 12	-0.85 (0.09)	-1.24 (0.06)
Change at Week 36	-1.01 (0.08)	-1.43 (0.06)
Change at Week 52	-1.04 (0.08)	-1.54 (0.06)

36. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	227
Change at Week 2	-0.60 (0.08)	-0.72 (0.06)
Change at Week 4	-0.74 (0.07)	-1.03 (0.05)
Change at Week 8	-0.91 (0.08)	-1.14 (0.06)
Change at Week 12	-0.89 (0.07)	-1.23 (0.05)
Change at Week 36	-1.09 (0.07)	-1.41 (0.05)
Change at Week 52	-1.09 (0.06)	-1.53 (0.05)

37. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	110	228
Change at Week 2	-0.78 (0.17)	-0.65 (0.12)
Change at Week 4	-0.99 (0.17)	-1.02 (0.13)
Change at Week 8	-1.24 (0.17)	-1.28 (0.13)
Change at Week 12	-0.93 (0.18)	-1.41 (0.13)
Change at Week 24	-1.43 (0.17)	-1.61 (0.13)
Change at Week 36	-1.37 (0.17)	-1.60 (0.13)
Change at Week 52	-1.59 (0.16)	-1.72 (0.12)

38. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	80	167
Change at Week 2	-0.75 (0.19)	-0.67 (0.14)
Change at Week 4	-1.02 (0.20)	-1.01 (0.15)
Change at Week 8	-1.15 (0.20)	-1.29 (0.14)
Change at Week 12	-1.02 (0.20)	-1.39 (0.14)
Change at Week 24	-1.25 (0.20)	-1.53 (0.15)
Change at Week 36	-1.20 (0.21)	-1.49 (0.15)
Change at Week 52	-1.45 (0.19)	-1.58 (0.14)

39. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (1.14 mL; for >30 kg bodyweight) or 100 mg (0.67 mL; for <=30 kg body weight), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller. 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).
Measure Participants	110	228
Change at Week 2	-0.13 (0.03)	-0.13 (0.02)
Change at Week 4	-0.16 (0.03)	-0.21 (0.03)
Change at Week 8	-0.21 (0.04)	-0.21 (0.03)
Change at Week 12	-0.17 (0.04)	-0.26 (0.03)
Change at Week 24	-0.23 (0.03)	-0.29 (0.02)
Change at Week 36	-0.25 (0.03)	-0.29 (0.02)
Change at Week 52	-0.26 (0.03)	-0.32 (0.02)

40. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (1.14 mL; for >30 kg bodyweight) or 100 mg (0.67 mL; for <=30 kg body weight), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller. 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).
Measure Participants	80	167
Change at Week 2	-0.15 (0.03)	-0.12 (0.02)
Change at Week 4	-0.19 (0.04)	-0.21 (0.03)
Change at Week 8	-0.22 (0.05)	-0.20 (0.04)
Change at Week 12	-0.16 (0.04)	-0.25 (0.03)
Change at Week 24	-0.21 (0.04)	-0.28 (0.03)
Change at Week 36	-0.25 (0.04)	-0.27 (0.03)
Change at Week 52	-0.26 (0.03)	-0.32 (0.02)

41. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	102	201
Change at Week 12	0.97 (0.09)	1.08 (0.07)
Change at Week 24	1.11 (0.09)	1.30 (0.07)
Change at Week 36	1.15 (0.09)	1.48 (0.07)
Change at Week 52	1.19 (0.08)	1.53 (0.06)

42. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	76	149
Change at Week 12	0.90 (0.10)	1.11 (0.08)
Change at Week 24	1.06 (0.10)	1.36 (0.08)
Change at Week 36	1.07 (0.10)	1.51 (0.08)
Change at Week 52	1.23 (0.09)	1.56 (0.07)

43. Secondary Outcome

Title	Healthcare Resource Utilization (HCRU): Number of School and Work Days Missed Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. For the caregiver data, population assessed was children participant only and the work days missed by their caregiver were counted.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy 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).	Dupilumab 200 mg (1.14 mL; for >30 kg bodyweight) or 100 mg (0.67 mL; for <=30 kg body weight), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller. 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).
Measure Participants	114	236
Number of missed school days	2.1 (4.2)	1.0 (2.3)
Number of missed work days	0.7 (1.9)	0.2 (0.8)

44. Secondary Outcome

Title	Healthcare Resource Utilization: Number of School and Work Days Missed Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. For the caregiver data, population assessed was children participant only and the work days missed by their caregiver were counted.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy 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).	Dupilumab 200 mg (1.14 mL; for >30 kg bodyweight) or 100 mg (0.67 mL; for <=30 kg body weight), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller. 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).
Measure Participants	84	175
Number of missed school days	2.0 (3.5)	0.9 (2.0)
Number of missed work days	0.6 (1.8)	0.2 (0.7)

45. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on type 2 inflammatory asthma phenotype population. For the caregiver data, population assessed was children participant only and the work days missed by their caregiver were counted.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy 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).	Dupilumab 200 mg (1.14 mL; for >30 kg bodyweight) or 100 mg (0.67 mL; for <=30 kg body weight), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller. 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).
Measure Participants	114	236
Percentage of participants with >=5 missed school days	17.5 13%	9.7 3.6%
Percentage of participants with >=5 missed work days	7 5.2%	0.8 0.3%

46. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. For the caregiver data, population assessed was children participant only and the work days missed by their caregiver were counted.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy 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).	Dupilumab 200 mg (1.14 mL; for >30 kg bodyweight) or 100 mg (0.67 mL; for <=30 kg body weight), SC injection q2w for 50 weeks in combination with stable-dose background therapy of medium-dose ICS therapy with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller. 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).
Measure Participants	84	175
Percentage of participants with >=5 missed school days	17.9 13.3%	8.6 3.2%
Percentage of participants with >=5 missed work days	6 4.4%	0.6 0.2%

47. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population which included all participants who actually received at least 1 dose or part of a dose of IMP and were analyzed according to the actually treatment received.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	134	271
Any TEAE	107 79.3%	225 82.4%
TESAE	6 4.4%	13 4.8%

48. Secondary Outcome

Title	Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PK population which consisted of all participants who actually received at least 1 dose or part of a dose of the IMP, analyzed according to the treatment actually received with at least one non-missing result for functional dupilumab concentration in serum. Here, 'number analyzed'=number of participants with available data for each specified category.

Arm/Group Title	Dupilumab 100mg q2w	Dupilumab 200mg q2w
Arm/Group Description	Dupilumab 100 mg (in 0.67 mL for <=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).	Dupilumab 200 mg (in 1.14 mL for >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).
Measure Participants	91	179
Baseline	0.00 (948.683)	0.00 (0.000)
Week 6	28566.81 (47.114)	50269.81 (46.667)
Week 12	37741.97 (46.516)	63476.17 (44.444)
Week 24	42283.09 (47.910)	49525.35 (52.806)
Week 52	41467.97 (49.368)	45295.35 (56.990)
Week 64	39.00 (0.000)	39.00 (0.000)

49. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Antidrug Antibodies (ADA) Response
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ADA population which consisted of all participants who actually received at least 1 dose or part of a dose of the IMP, analyzed according to the treatment actually received and had at least one non-missing ADA result (either ADA negative or ADA positive) in the ADA assay after the first dose of IMP. Data for this outcome measure was planned to be collected and analyzed separately for dupilumab 100 mg and 200 mg dose.

Arm/Group Title	Placebo	Dupilumab 100mg q2w	Dupilumab 200mg q2w
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 100 mg (in 0.67 mL for <=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).	Dupilumab 200 mg (in 1.14 mL for >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).
Measure Participants	133	91	178
Treatment-emergent ADA	3.0 2.2%	4.4 1.6%	7.3 1.8%
Treatment-boosted ADA	0 0%	0 0%	0 0%

50. Secondary Outcome

Title	Percentage of Participants With Seroconversion
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population.

Arm/Group Title	Placebo	Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).	Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
Measure Participants	134	271
Number [percentage of participants]	62.5 46.3%	79.6 29.2%

Adverse Events

Time Frame	All AEs were collected from signature of the informed consent form up to end of post treatment period (i.e., up to Week 64) regardless of seriousness or relationship to IMP.
Adverse Event Reporting Description	Reported AEs were treatment emergent AEs that developed/worsened in grade or became serious during during 'TEAE period' (from the time of first dose of study drug to the end of post-treatment period [i.e., up to Week 64]). Analysis was performed on safety population.
Arm/Group Title	Placebo		Dupilumab
Arm/Group Description	Placebo (for Dupilumab), 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).		Dupilumab 200 mg (in 1.14 mL for >30 kg BW) or 100 mg (in 0.67 mL for <=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).
All Cause Mortality
	Placebo		Dupilumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/134 (0%)		0/271 (0%)
Serious Adverse Events
	Placebo		Dupilumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/134 (4.5%)		13/271 (4.8%)
Blood and lymphatic system disorders
Eosinophilia	0/134 (0%)	0	2/271 (0.7%)	2
Immune Thrombocytopenia	1/134 (0.7%)	1	0/271 (0%)	0
Eye disorders
Vision Blurred	0/134 (0%)	0	1/271 (0.4%)	1
Immune system disorders
Allergy To Chemicals	0/134 (0%)	0	1/271 (0.4%)	1
Anaphylactic Reaction	1/134 (0.7%)	1	0/271 (0%)	0
Drug Hypersensitivity	0/134 (0%)	0	1/271 (0.4%)	1
Milk Allergy	0/134 (0%)	0	1/271 (0.4%)	1
Infections and infestations
Furuncle	0/134 (0%)	0	1/271 (0.4%)	1
Gastroenteritis	1/134 (0.7%)	1	0/271 (0%)	0
Gastrointestinal Viral Infection	1/134 (0.7%)	1	0/271 (0%)	0
Lymphadenitis Viral	1/134 (0.7%)	1	0/271 (0%)	0
Parainfluenzae Virus Infection	1/134 (0.7%)	1	0/271 (0%)	0
Pharyngitis	0/134 (0%)	0	1/271 (0.4%)	1
Pneumonia	0/134 (0%)	0	1/271 (0.4%)	1
Injury, poisoning and procedural complications
Hand Fracture	0/134 (0%)	0	1/271 (0.4%)	1
Nervous system disorders
Headache	0/134 (0%)	0	1/271 (0.4%)	1
Partial Seizures	1/134 (0.7%)	1	0/271 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/134 (0%)	0	4/271 (1.5%)	4
Atelectasis	1/134 (0.7%)	1	0/271 (0%)	0
Bronchospasm	1/134 (0.7%)	1	0/271 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Dupilumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	89/134 (66.4%)		161/271 (59.4%)
Blood and lymphatic system disorders
Eosinophilia	1/134 (0.7%)	1	15/271 (5.5%)	15
General disorders
Injection Site Erythema	13/134 (9.7%)	93	35/271 (12.9%)	153
Injection Site Oedema	7/134 (5.2%)	15	28/271 (10.3%)	72
Infections and infestations
Bronchitis	14/134 (10.4%)	22	17/271 (6.3%)	21
Influenza	12/134 (9%)	17	20/271 (7.4%)	22
Nasopharyngitis	29/134 (21.6%)	45	50/271 (18.5%)	76
Pharyngitis	14/134 (10.4%)	19	23/271 (8.5%)	27
Sinusitis	7/134 (5.2%)	10	9/271 (3.3%)	11
Upper Respiratory Tract Infection	18/134 (13.4%)	30	35/271 (12.9%)	59
Viral Upper Respiratory Tract Infection	13/134 (9.7%)	17	33/271 (12.2%)	41
Nervous system disorders
Headache	10/134 (7.5%)	17	18/271 (6.6%)	29
Respiratory, thoracic and mediastinal disorders
Cough	9/134 (6.7%)	10	15/271 (5.5%)	17
Rhinitis Allergic	16/134 (11.9%)	19	16/271 (5.9%)	27

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.