Trial Outcomes & Findings for Evaluation of Dupilumab in Children With Uncontrolled Asthma (NCT NCT02948959)

NCT ID: NCT02948959

Last Updated: 2022-03-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 408 participants
• Primary outcome timeframe: Baseline to Week 52
• Results posted on: 2022-03-28

Participant Flow

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.

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.

Participant milestones

Measure	Placebo 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 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).
52 Weeks Treatment Period STARTED	135	273
52 Weeks Treatment Period Treated	135	270
52 Weeks Treatment Period Safety Population	134	271
52 Weeks Treatment Period Type 2 Inflammatory Asthma Phenotype Population	114	236
52 Weeks Treatment Period Baseline Blood Eosinophils Count >=300 Cells Per Microlitre Population	84	175
52 Weeks Treatment Period COMPLETED	130	248
52 Weeks Treatment Period NOT COMPLETED	5	25
12 Weeks Follow-up Period STARTED	9	31
12 Weeks Follow-up Period COMPLETED	4	19
12 Weeks Follow-up Period NOT COMPLETED	5	12

Reasons for withdrawal

Measure	Placebo 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 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).
52 Weeks Treatment Period Poor compliance to protocol	0	2
52 Weeks Treatment Period Adverse Event	2	5
52 Weeks Treatment Period Withdrawal by Subject	2	2
52 Weeks Treatment Period Participant used protocol prohibited vaccine	1	6
52 Weeks Treatment Period Randomized by error	0	5
52 Weeks Treatment Period Randomized and not treated	0	3
52 Weeks Treatment Period Non-compliant to study treatment	0	1
52 Weeks Treatment Period Change of residence location	0	1
12 Weeks Follow-up Period Adverse Event	0	2
12 Weeks Follow-up Period Poor compliance to protocol	1	2
12 Weeks Follow-up Period Withdrawal by Subject	3	3
12 Weeks Follow-up Period Randomized by error	0	3
12 Weeks Follow-up Period Change of residence location	0	2
12 Weeks Follow-up Period Study site closure	1	0

Baseline Characteristics

Evaluation of Dupilumab in Children With Uncontrolled Asthma

Baseline characteristics by cohort

Measure	Placebo n=135 Participants 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 n=273 Participants 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 n=408 Participants Total of all reporting groups
Age, Continuous	8.9 years STANDARD_DEVIATION 1.6 • n=5 Participants	8.9 years STANDARD_DEVIATION 1.7 • n=7 Participants	8.9 years STANDARD_DEVIATION 1.6 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	98 Participants n=7 Participants	146 Participants n=5 Participants
Sex: Female, Male Male	87 Participants n=5 Participants	175 Participants n=7 Participants	262 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	118 Participants n=5 Participants	242 Participants n=7 Participants	360 Participants n=5 Participants
Race/Ethnicity, Customized Black/of African descent	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	8 Participants n=5 Participants	17 Participants n=7 Participants	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: 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.

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.

Outcome measures

Measure	Placebo n=84 Participants 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 n=175 Participants 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).	Dupilumab 200mg q2w 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).
Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population	0.665 exacerbations per participant-years Interval 0.467 to 0.949	0.235 exacerbations per participant-years Interval 0.16 to 0.345	—

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: 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.

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.

Outcome measures

Measure	Placebo n=114 Participants 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 n=236 Participants 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).	Dupilumab 200mg q2w 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).
Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population	0.748 exacerbations per participant-years Interval 0.542 to 1.034	0.305 exacerbations per participant-years Interval 0.223 to 0.416	—

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=168 Participants 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).	Dupilumab 200mg q2w 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).
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	4.83 percent predicted FEV1 Standard Error 1.54	10.15 percent predicted FEV1 Standard Error 1.12	—

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=229 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 12: Type 2 Inflammatory Asthma Phenotype Population	5.32 percent predicted FEV1 Standard Error 1.36	10.53 percent predicted FEV1 Standard Error 1.01	—

SECONDARY outcome

Timeframe: Baseline, Week 24

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=166 Participants 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).	Dupilumab 200mg q2w 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).
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	-0.88 score on a scale Standard Error 0.09	-1.34 score on a scale Standard Error 0.06	—

SECONDARY outcome

Timeframe: Baseline, Week 24

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=227 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Type 2 Inflammatory Asthma Phenotype Population	-0.99 score on a scale Standard Error 0.07	-1.32 score on a scale Standard Error 0.05	—

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: 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.

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=165 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population	-0.81 parts per billion Standard Error 1.69	-21.40 parts per billion Standard Error 1.21	—

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=226 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Type 2 Inflammatory Asthma Phenotype Population	-1.13 parts per billion Standard Error 1.43	-18.97 parts per billion Standard Error 1.04	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=229 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	4.84 percent predicted FEV1 Standard Error 1.29	8.11 percent predicted FEV1 Standard Error 0.95	—
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 Change at Week 4	3.55 percent predicted FEV1 Standard Error 1.30	9.97 percent predicted FEV1 Standard Error 0.97	—
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 Change at Week 8	4.27 percent predicted FEV1 Standard Error 1.29	10.27 percent predicted FEV1 Standard Error 0.96	—
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 Change at Week 24	4.27 percent predicted FEV1 Standard Error 1.40	10.92 percent predicted FEV1 Standard Error 1.04	—
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 Change at Week 36	6.63 percent predicted FEV1 Standard Error 1.49	11.46 percent predicted FEV1 Standard Error 1.10	—
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 Change at Week 52	4.36 percent predicted FEV1 Standard Error 1.50	12.15 percent predicted FEV1 Standard Error 1.10	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=168 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	3.94 percent predicted of FEV1 Standard Error 1.51	7.49 percent predicted of FEV1 Standard Error 1.08	—
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 Change at Week 4	2.19 percent predicted of FEV1 Standard Error 1.53	9.09 percent predicted of FEV1 Standard Error 1.12	—
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 Change at Week 8	2.48 percent predicted of FEV1 Standard Error 1.42	9.75 percent predicted of FEV1 Standard Error 1.04	—
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 Change at Week 24	3.45 percent predicted of FEV1 Standard Error 1.63	11.10 percent predicted of FEV1 Standard Error 1.19	—
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 Change at Week 36	6.87 percent predicted of FEV1 Standard Error 1.81	11.47 percent predicted of FEV1 Standard Error 1.31	—
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 Change at Week 52	4.08 percent predicted of FEV1 Standard Error 1.80	12.43 percent predicted of FEV1 Standard Error 1.30	—

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on type 2 inflammatory asthma phenotype population.

The time to first severe exacerbation was defined as date of the first severe exacerbation event - randomization date +1. A severe asthma exacerbation event was defined as a deterioration of asthma during the 52-week treatment period requiring: use of systemic corticosteroids for >=3 days; and/or hospitalization related to asthma symptoms or emergency room visit because of asthma requiring systemic corticosteroid treatment. Kaplan-Meier method was used for analysis.

Outcome measures

Measure	Placebo n=114 Participants 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 n=236 Participants 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).	Dupilumab 200mg q2w 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).
Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population	NA days Interval 366.0 to Median and upper limit of 95% confidence interval (CI) was not estimable due to less than 50% of participants with events.	NA days Median, lower and upper limit of 95 % CI was not estimable due to less than 50% of participants with events.	—

SECONDARY outcome

Timeframe: Baseline up to Week 52

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

The time to first severe exacerbation was defined as date of the first severe exacerbation event - randomization date +1. A severe asthma exacerbation event was defined as a deterioration of asthma during the 52-week treatment period requiring: use of systemic corticosteroids for >=3 days; and/or hospitalization related to asthma symptoms or emergency room visit because of asthma requiring systemic corticosteroid treatment. Kaplan-Meier method was used for analysis.

Outcome measures

Measure	Placebo n=84 Participants 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 n=175 Participants 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).	Dupilumab 200mg q2w 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).
Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population	366.0 days Interval 265.0 to Upper limit of 95 % CI was not estimable due to less than 50% of participants with events.	NA days Median, lower and upper limit of 95 % CI was not estimable due to less than 50% of participants with events.	—

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on type 2 inflammatory asthma phenotype population.

Time to first LOAC event was date of first LOAC event - first dose date +1. A LOAC event was defined as deterioration of asthma during 52-week treatment period that resulted in any of the following: >= 6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS dose >=4 times than dose at Visit 2 (Week 0); a decrease in ante meridiem (AM)/post meridiem (PM) peak flow of 30% or more on 2 consecutive days of treatment, based on defined stability limit (defined as respective mean AM/PM peak expiratory flow obtained over last 7 days prior to randomization (Day 1); severe exacerbation event. Kaplan-Meier method was used for analysis.

Outcome measures

Measure	Placebo n=114 Participants 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 n=236 Participants 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).	Dupilumab 200mg q2w 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).
Time to First Loss of Asthma Control (LOAC) Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population	63.5 days Interval 42.0 to 84.0	140.0 days Interval 103.0 to 217.0	—

SECONDARY outcome

Timeframe: Baseline up to Week 52

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

Time to first LOAC event was date of first LOAC event - first dose date +1. A LOAC event was defined as deterioration of asthma during 52-week treatment period that resulted in any of the following: >= 6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS dose >=4 times than dose at Visit 2 (Week 0); a decrease in AM/PM peak flow of 30% or more on 2 consecutive days of treatment, based on defined stability limit (defined as respective mean AM/PM peak expiratory flow obtained over last 7 days prior to randomization (Day 1); severe exacerbation event. Kaplan-Meier method was used for analysis.

Outcome measures

Measure	Placebo n=84 Participants 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 n=175 Participants 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).	Dupilumab 200mg q2w 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).
Time to First Loss of Asthma Control Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population	47.5 days Interval 38.0 to 84.0	135.0 days Interval 82.0 to 219.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=229 Participants 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).	Dupilumab 200mg q2w 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).
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 2	0.08 liters Standard Error 0.03	0.14 liters Standard Error 0.02	—
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 4	0.06 liters Standard Error 0.03	0.18 liters Standard Error 0.02	—
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 8	0.09 liters Standard Error 0.03	0.21 liters Standard Error 0.02	—
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 12	0.12 liters Standard Error 0.03	0.22 liters Standard Error 0.02	—
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 24	0.14 liters Standard Error 0.03	0.27 liters Standard Error 0.02	—
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 36	0.23 liters Standard Error 0.03	0.33 liters Standard Error 0.02	—
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 52	0.24 liters Standard Error 0.03	0.41 liters Standard Error 0.02	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=168 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	0.07 liters Standard Error 0.03	0.13 liters Standard Error 0.02	—
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 Change at Week 4	0.04 liters Standard Error 0.03	0.17 liters Standard Error 0.02	—
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 Change at Week 8	0.06 liters Standard Error 0.03	0.20 liters Standard Error 0.02	—
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 Change at Week 12	0.12 liters Standard Error 0.03	0.22 liters Standard Error 0.02	—
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 Change at Week 24	0.13 liters Standard Error 0.03	0.28 liters Standard Error 0.03	—
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 Change at Week 36	0.24 liters Standard Error 0.04	0.33 liters Standard Error 0.03	—
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 Change at Week 52	0.25 liters Standard Error 0.04	0.42 liters Standard Error 0.03	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=229 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	8.07 percent change Standard Error 2.00	13.38 percent change Standard Error 1.47	—
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 Change at Week 4	6.73 percent change Standard Error 2.10	16.01 percent change Standard Error 1.55	—
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 Change at Week 8	7.68 percent change Standard Error 1.87	16.33 percent change Standard Error 1.41	—
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 Change at Week 12	8.87 percent change Standard Error 2.10	16.94 percent change Standard Error 1.56	—
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 Change at Week 24	7.66 percent change Standard Error 2.12	17.61 percent change Standard Error 1.57	—
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 Change at Week 36	10.88 percent change Standard Error 2.85	19.19 percent change Standard Error 2.06	—
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 Change at Week 52	7.92 percent change Standard Error 2.81	20.06 percent change Standard Error 2.03	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=168 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 36	12.15 percent change Standard Error 3.67	19.65 percent change Standard Error 2.61	—
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 Change at Week 2	7.55 percent change Standard Error 2.41	12.76 percent change Standard Error 1.73	—
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 Change at Week 4	5.81 percent change Standard Error 2.57	15.20 percent change Standard Error 1.87	—
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 Change at Week 8	6.09 percent change Standard Error 2.10	16.01 percent change Standard Error 1.56	—
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 Change at Week 12	9.56 percent change Standard Error 2.45	17.14 percent change Standard Error 1.79	—
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 Change at Week 24	7.44 percent change Standard Error 2.54	18.09 percent change Standard Error 1.85	—
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 Change at Week 52	8.50 percent change Standard Error 3.58	20.97 percent change Standard Error 2.54	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=228 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	5.57 liters/minute Standard Error 2.66	6.50 liters/minute Standard Error 2.00	—
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 Change at Week 4	7.10 liters/minute Standard Error 3.31	12.81 liters/minute Standard Error 2.43	—
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 Change at Week 8	7.37 liters/minute Standard Error 3.56	18.05 liters/minute Standard Error 2.59	—
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 Change at Week 12	5.37 liters/minute Standard Error 3.93	19.38 liters/minute Standard Error 2.85	—
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 Change at Week 24	8.76 liters/minute Standard Error 4.53	23.32 liters/minute Standard Error 3.25	—
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 Change at Week 36	17.70 liters/minute Standard Error 4.99	26.77 liters/minute Standard Error 3.56	—
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 Change at Week 52	19.88 liters/minute Standard Error 5.16	31.45 liters/minute Standard Error 3.69	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=228 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 8	5.52 liters/minute Standard Error 3.60	20.17 liters/minute Standard Error 2.64	—
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 Change at Week 12	1.71 liters/minute Standard Error 3.92	19.68 liters/minute Standard Error 2.85	—
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 Change at Week 24	3.78 liters/minute Standard Error 4.61	22.75 liters/minute Standard Error 3.32	—
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 Change at Week 36	12.55 liters/minute Standard Error 5.06	24.69 liters/minute Standard Error 3.62	—
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 Change at Week 52	16.46 liters/minute Standard Error 5.20	28.20 liters/minute Standard Error 3.73	—
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 Change at Week 2	7.62 liters/minute Standard Error 2.94	10.60 liters/minute Standard Error 2.20	—
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 Change at Week 4	6.92 liters/minute Standard Error 3.42	15.23 liters/minute Standard Error 2.52	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=167 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 4	5.62 liters/minute Standard Error 3.80	11.75 liters/minute Standard Error 2.76	—
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 Change at Week 8	5.54 liters/minute Standard Error 4.09	17.32 liters/minute Standard Error 2.96	—
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 Change at Week 12	4.77 liters/minute Standard Error 4.65	19.25 liters/minute Standard Error 3.34	—
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 Change at Week 24	4.78 liters/minute Standard Error 5.05	23.62 liters/minute Standard Error 3.61	—
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 Change at Week 36	14.80 liters/minute Standard Error 5.77	26.78 liters/minute Standard Error 4.08	—
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 Change at Week 52	19.75 liters/minute Standard Error 6.33	32.80 liters/minute Standard Error 4.49	—
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 Change at Week 2	5.85 liters/minute Standard Error 2.97	7.94 liters/minute Standard Error 2.21	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=167 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	5.64 liters/minute Standard Error 3.42	10.02 liters/minute Standard Error 2.53	—
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 Change at Week 4	4.36 liters/minute Standard Error 3.96	13.09 liters/minute Standard Error 2.89	—
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 Change at Week 8	0.92 liters/minute Standard Error 4.05	17.51 liters/minute Standard Error 2.96	—
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 Change at Week 12	-1.37 liters/minute Standard Error 4.57	17.73 liters/minute Standard Error 3.30	—
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 Change at Week 24	-1.37 liters/minute Standard Error 5.21	20.30 liters/minute Standard Error 3.74	—
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 Change at Week 36	7.52 liters/minute Standard Error 6.01	23.23 liters/minute Standard Error 4.26	—
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 Change at Week 52	14.67 liters/minute Standard Error 6.39	26.60 liters/minute Standard Error 4.54	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=229 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 2	0.07 liters Standard Error 0.02	0.07 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 4	0.07 liters Standard Error 0.03	0.11 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 12	0.12 liters Standard Error 0.03	0.14 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 24	0.16 liters Standard Error 0.03	0.20 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 36	0.22 liters Standard Error 0.03	0.28 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 52	0.27 liters Standard Error 0.03	0.37 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 8	0.10 liters Standard Error 0.02	0.13 liters Standard Error 0.02	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=168 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Change at Week 2	0.07 liters Standard Error 0.03	0.06 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Change at Week 4	0.08 liters Standard Error 0.03	0.09 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Change at Week 8	0.09 liters Standard Error 0.03	0.13 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Change at Week 12	0.13 liters Standard Error 0.03	0.14 liters Standard Error 0.02	—
Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Change at Week 24	0.17 liters Standard Error 0.03	0.22 liters Standard Error 0.03	—
Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Change at Week 36	0.24 liters Standard Error 0.04	0.28 liters Standard Error 0.03	—
Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Change at Week 52	0.29 liters Standard Error 0.04	0.38 liters Standard Error 0.03	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=229 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	0.11 liters/second Standard Error 0.05	0.28 liters/second Standard Error 0.04	—
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 Change at Week 4	0.07 liters/second Standard Error 0.05	0.34 liters/second Standard Error 0.04	—
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 Change at Week 8	0.10 liters/second Standard Error 0.05	0.39 liters/second Standard Error 0.04	—
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 Change at Week 12	0.14 liters/second Standard Error 0.05	0.41 liters/second Standard Error 0.04	—
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 Change at Week 24	0.16 liters/second Standard Error 0.05	0.44 liters/second Standard Error 0.04	—
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 Change at Week 36	0.29 liters/second Standard Error 0.05	0.49 liters/second Standard Error 0.04	—
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 Change at Week 52	0.29 liters/second Standard Error 0.06	0.60 liters/second Standard Error 0.04	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=168 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	0.07 liters/second Standard Error 0.05	0.29 liters/second Standard Error 0.04	—
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 Change at Week 4	0.00 liters/second Standard Error 0.05	0.33 liters/second Standard Error 0.04	—
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 Change at Week 8	0.02 liters/second Standard Error 0.06	0.40 liters/second Standard Error 0.04	—
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 Change at Week 12	0.10 liters/second Standard Error 0.05	0.42 liters/second Standard Error 0.04	—
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 Change at Week 24	0.12 liters/second Standard Error 0.06	0.47 liters/second Standard Error 0.04	—
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 Change at Week 36	0.27 liters/second Standard Error 0.06	0.51 liters/second Standard Error 0.05	—
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 Change at Week 52	0.26 liters/second Standard Error 0.07	0.65 liters/second Standard Error 0.05	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=230 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 2	0.61 liters Standard Error 1.26	1.51 liters Standard Error 0.92	—
Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 4	-0.02 liters Standard Error 1.15	2.42 liters Standard Error 0.86	—
Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 8	-0.79 liters Standard Error 1.21	2.85 liters Standard Error 0.90	—
Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 12	-0.32 liters Standard Error 1.23	2.48 liters Standard Error 0.91	—
Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 24	-0.50 liters Standard Error 1.31	2.60 liters Standard Error 0.96	—
Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 36	0.55 liters Standard Error 1.46	3.15 liters Standard Error 1.07	—
Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 52	-0.75 liters Standard Error 1.48	3.62 liters Standard Error 1.08	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=169 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	0.10 liters Standard Error 1.49	0.52 liters Standard Error 1.07	—
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 Change at Week 4	-0.29 liters Standard Error 1.35	1.44 liters Standard Error 1.00	—
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 Change at Week 8	-2.05 liters Standard Error 1.31	1.81 liters Standard Error 0.98	—
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 Change at Week 12	-0.61 liters Standard Error 1.44	2.28 liters Standard Error 1.04	—
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 Change at Week 24	-0.80 liters Standard Error 1.54	2.25 liters Standard Error 1.12	—
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 Change at Week 36	0.72 liters Standard Error 1.80	2.87 liters Standard Error 1.31	—
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 Change at Week 52	-0.52 liters Standard Error 1.79	3.13 liters Standard Error 1.30	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=228 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 2	-0.22 score on a scale Standard Error 0.04	-0.18 score on a scale Standard Error 0.03	—
Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 4	-0.29 score on a scale Standard Error 0.05	-0.34 score on a scale Standard Error 0.04	—
Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 8	-0.37 score on a scale Standard Error 0.05	-0.39 score on a scale Standard Error 0.04	—
Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 12	-0.34 score on a scale Standard Error 0.05	-0.48 score on a scale Standard Error 0.04	—
Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 24	-0.46 score on a scale Standard Error 0.05	-0.56 score on a scale Standard Error 0.04	—
Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 36	-0.48 score on a scale Standard Error 0.05	-0.56 score on a scale Standard Error 0.04	—
Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 52	-0.50 score on a scale Standard Error 0.05	-0.61 score on a scale Standard Error 0.04	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=228 Participants 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).	Dupilumab 200mg q2w 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).
Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 2	-0.17 score on a scale Standard Error 0.05	-0.13 score on a scale Standard Error 0.03	—
Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 4	-0.25 score on a scale Standard Error 0.05	-0.29 score on a scale Standard Error 0.04	—
Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 8	-0.33 score on a scale Standard Error 0.06	-0.40 score on a scale Standard Error 0.04	—
Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 12	-0.30 score on a scale Standard Error 0.06	-0.45 score on a scale Standard Error 0.04	—
Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 24	-0.44 score on a scale Standard Error 0.06	-0.53 score on a scale Standard Error 0.04	—
Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 36	-0.47 score on a scale Standard Error 0.06	-0.55 score on a scale Standard Error 0.04	—
Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population Change at Week 52	-0.50 score on a scale Standard Error 0.06	-0.59 score on a scale Standard Error 0.04	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=167 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	-0.24 score on a scale Standard Error 0.05	-0.20 score on a scale Standard Error 0.04	—
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 Change at Week 4	-0.32 score on a scale Standard Error 0.06	-0.34 score on a scale Standard Error 0.04	—
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 Change at Week 8	-0.38 score on a scale Standard Error 0.06	-0.40 score on a scale Standard Error 0.05	—
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 Change at Week 12	-0.33 score on a scale Standard Error 0.06	-0.48 score on a scale Standard Error 0.04	—
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 Change at Week 24	-0.45 score on a scale Standard Error 0.06	-0.55 score on a scale Standard Error 0.04	—
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 Change at Week 36	-0.46 score on a scale Standard Error 0.06	-0.56 score on a scale Standard Error 0.04	—
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 Change at Week 52	-0.50 score on a scale Standard Error 0.06	-0.62 score on a scale Standard Error 0.04	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=167 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	-0.18 score on a scale Standard Error 0.05	-0.15 score on a scale Standard Error 0.04	—
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 Change at Week 4	-0.27 score on a scale Standard Error 0.06	-0.29 score on a scale Standard Error 0.04	—
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 Change at Week 8	-0.30 score on a scale Standard Error 0.06	-0.41 score on a scale Standard Error 0.05	—
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 Change at Week 12	-0.29 score on a scale Standard Error 0.07	-0.48 score on a scale Standard Error 0.05	—
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 Change at Week 24	-0.42 score on a scale Standard Error 0.06	-0.53 score on a scale Standard Error 0.05	—
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 Change at Week 36	-0.43 score on a scale Standard Error 0.06	-0.56 score on a scale Standard Error 0.05	—
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 Change at Week 52	-0.51 score on a scale Standard Error 0.06	-0.60 score on a scale Standard Error 0.04	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=227 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	-0.72 score on a scale Standard Error 0.09	-0.77 score on a scale Standard Error 0.06	—
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 Change at Week 4	-0.86 score on a scale Standard Error 0.08	-1.09 score on a scale Standard Error 0.06	—
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 Change at Week 8	-1.04 score on a scale Standard Error 0.09	-1.24 score on a scale Standard Error 0.07	—
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 Change at Week 12	-1.04 score on a scale Standard Error 0.08	-1.35 score on a scale Standard Error 0.06	—
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 Change at Week 24	-1.18 score on a scale Standard Error 0.08	-1.46 score on a scale Standard Error 0.06	—
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 Change at Week 36	-1.25 score on a scale Standard Error 0.08	-1.57 score on a scale Standard Error 0.06	—
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 Change at Week 52	-1.30 score on a scale Standard Error 0.07	-1.70 score on a scale Standard Error 0.05	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=166 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	-0.63 score on a scale Standard Error 0.11	-0.76 score on a scale Standard Error 0.08	—
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 Change at Week 4	-0.75 score on a scale Standard Error 0.10	-1.10 score on a scale Standard Error 0.07	—
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 Change at Week 8	-0.98 score on a scale Standard Error 0.10	-1.27 score on a scale Standard Error 0.07	—
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 Change at Week 12	-1.00 score on a scale Standard Error 0.10	-1.37 score on a scale Standard Error 0.07	—
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 Change at Week 24	-1.06 score on a scale Standard Error 0.09	-1.48 score on a scale Standard Error 0.07	—
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 Change at Week 36	-1.17 score on a scale Standard Error 0.09	-1.59 score on a scale Standard Error 0.07	—
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 Change at Week 52	-1.25 score on a scale Standard Error 0.08	-1.71 score on a scale Standard Error 0.06	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8,12, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=166 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	-0.50 score on a scale Standard Error 0.09	-0.70 score on a scale Standard Error 0.07	—
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 Change at Week 4	-0.64 score on a scale Standard Error 0.09	-1.02 score on a scale Standard Error 0.06	—
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 Change at Week 8	-0.83 score on a scale Standard Error 0.09	-1.16 score on a scale Standard Error 0.06	—
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 Change at Week 12	-0.85 score on a scale Standard Error 0.09	-1.24 score on a scale Standard Error 0.06	—
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 Change at Week 36	-1.01 score on a scale Standard Error 0.08	-1.43 score on a scale Standard Error 0.06	—
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 Change at Week 52	-1.04 score on a scale Standard Error 0.08	-1.54 score on a scale Standard Error 0.06	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8,12, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=227 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 4	-0.74 score on a scale Standard Error 0.07	-1.03 score on a scale Standard Error 0.05	—
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 Change at Week 8	-0.91 score on a scale Standard Error 0.08	-1.14 score on a scale Standard Error 0.06	—
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 Change at Week 12	-0.89 score on a scale Standard Error 0.07	-1.23 score on a scale Standard Error 0.05	—
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 Change at Week 36	-1.09 score on a scale Standard Error 0.07	-1.41 score on a scale Standard Error 0.05	—
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 Change at Week 52	-1.09 score on a scale Standard Error 0.06	-1.53 score on a scale Standard Error 0.05	—
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 Change at Week 2	-0.60 score on a scale Standard Error 0.08	-0.72 score on a scale Standard Error 0.06	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=228 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	-0.78 puffs of reliever medication per 24 hour Standard Error 0.17	-0.65 puffs of reliever medication per 24 hour Standard Error 0.12	—
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 Change at Week 4	-0.99 puffs of reliever medication per 24 hour Standard Error 0.17	-1.02 puffs of reliever medication per 24 hour Standard Error 0.13	—
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 Change at Week 8	-1.24 puffs of reliever medication per 24 hour Standard Error 0.17	-1.28 puffs of reliever medication per 24 hour Standard Error 0.13	—
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 Change at Week 12	-0.93 puffs of reliever medication per 24 hour Standard Error 0.18	-1.41 puffs of reliever medication per 24 hour Standard Error 0.13	—
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 Change at Week 36	-1.37 puffs of reliever medication per 24 hour Standard Error 0.17	-1.60 puffs of reliever medication per 24 hour Standard Error 0.13	—
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 Change at Week 52	-1.59 puffs of reliever medication per 24 hour Standard Error 0.16	-1.72 puffs of reliever medication per 24 hour Standard Error 0.12	—
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 Change at Week 24	-1.43 puffs of reliever medication per 24 hour Standard Error 0.17	-1.61 puffs of reliever medication per 24 hour Standard Error 0.13	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=167 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 4	-1.02 puffs of reliever medication per 24 hour Standard Error 0.20	-1.01 puffs of reliever medication per 24 hour Standard Error 0.15	—
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 Change at Week 8	-1.15 puffs of reliever medication per 24 hour Standard Error 0.20	-1.29 puffs of reliever medication per 24 hour Standard Error 0.14	—
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 Change at Week 12	-1.02 puffs of reliever medication per 24 hour Standard Error 0.20	-1.39 puffs of reliever medication per 24 hour Standard Error 0.14	—
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 Change at Week 24	-1.25 puffs of reliever medication per 24 hour Standard Error 0.20	-1.53 puffs of reliever medication per 24 hour Standard Error 0.15	—
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 Change at Week 36	-1.20 puffs of reliever medication per 24 hour Standard Error 0.21	-1.49 puffs of reliever medication per 24 hour Standard Error 0.15	—
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 Change at Week 52	-1.45 puffs of reliever medication per 24 hour Standard Error 0.19	-1.58 puffs of reliever medication per 24 hour Standard Error 0.14	—
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 Change at Week 2	-0.75 puffs of reliever medication per 24 hour Standard Error 0.19	-0.67 puffs of reliever medication per 24 hour Standard Error 0.14	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=110 Participants 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 n=228 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	-0.13 nocturnal awakenings per night Standard Error 0.03	-0.13 nocturnal awakenings per night Standard Error 0.02	—
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 Change at Week 4	-0.16 nocturnal awakenings per night Standard Error 0.03	-0.21 nocturnal awakenings per night Standard Error 0.03	—
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 Change at Week 8	-0.21 nocturnal awakenings per night Standard Error 0.04	-0.21 nocturnal awakenings per night Standard Error 0.03	—
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 Change at Week 12	-0.17 nocturnal awakenings per night Standard Error 0.04	-0.26 nocturnal awakenings per night Standard Error 0.03	—
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 Change at Week 24	-0.23 nocturnal awakenings per night Standard Error 0.03	-0.29 nocturnal awakenings per night Standard Error 0.02	—
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 Change at Week 36	-0.25 nocturnal awakenings per night Standard Error 0.03	-0.29 nocturnal awakenings per night Standard Error 0.02	—
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 Change at Week 52	-0.26 nocturnal awakenings per night Standard Error 0.03	-0.32 nocturnal awakenings per night Standard Error 0.02	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=80 Participants 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 n=167 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 2	-0.15 nocturnal awakenings per night Standard Error 0.03	-0.12 nocturnal awakenings per night Standard Error 0.02	—
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 Change at Week 4	-0.19 nocturnal awakenings per night Standard Error 0.04	-0.21 nocturnal awakenings per night Standard Error 0.03	—
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 Change at Week 8	-0.22 nocturnal awakenings per night Standard Error 0.05	-0.20 nocturnal awakenings per night Standard Error 0.04	—
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 Change at Week 12	-0.16 nocturnal awakenings per night Standard Error 0.04	-0.25 nocturnal awakenings per night Standard Error 0.03	—
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 Change at Week 24	-0.21 nocturnal awakenings per night Standard Error 0.04	-0.28 nocturnal awakenings per night Standard Error 0.03	—
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 Change at Week 36	-0.25 nocturnal awakenings per night Standard Error 0.04	-0.27 nocturnal awakenings per night Standard Error 0.03	—
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 Change at Week 52	-0.26 nocturnal awakenings per night Standard Error 0.03	-0.32 nocturnal awakenings per night Standard Error 0.02	—

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=102 Participants 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 n=201 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 12	0.97 score on a scale Standard Error 0.09	1.08 score on a scale Standard Error 0.07	—
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 Change at Week 24	1.11 score on a scale Standard Error 0.09	1.30 score on a scale Standard Error 0.07	—
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 Change at Week 36	1.15 score on a scale Standard Error 0.09	1.48 score on a scale Standard Error 0.07	—
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 Change at Week 52	1.19 score on a scale Standard Error 0.08	1.53 score on a scale Standard Error 0.06	—

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 52

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

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.

Outcome measures

Measure	Placebo n=76 Participants 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 n=149 Participants 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).	Dupilumab 200mg q2w 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).
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 Change at Week 12	0.90 score on a scale Standard Error 0.10	1.11 score on a scale Standard Error 0.08	—
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 Change at Week 24	1.06 score on a scale Standard Error 0.10	1.36 score on a scale Standard Error 0.08	—
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 Change at Week 36	1.07 score on a scale Standard Error 0.10	1.51 score on a scale Standard Error 0.08	—
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 Change at Week 52	1.23 score on a scale Standard Error 0.09	1.56 score on a scale Standard Error 0.07	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: 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.

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).

Outcome measures

Measure	Placebo n=114 Participants 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 n=236 Participants 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).	Dupilumab 200mg q2w 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).
Healthcare Resource Utilization (HCRU): Number of School and Work Days Missed Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population Number of missed school days	2.1 days Standard Deviation 4.2	1.0 days Standard Deviation 2.3	—
Healthcare Resource Utilization (HCRU): Number of School and Work Days Missed Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population Number of missed work days	0.7 days Standard Deviation 1.9	0.2 days Standard Deviation 0.8	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: 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.

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.

Outcome measures

Measure	Placebo n=84 Participants 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 n=175 Participants 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).	Dupilumab 200mg q2w 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).
Healthcare Resource Utilization: Number of School and Work Days Missed Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Number of missed school days	2.0 days Standard Deviation 3.5	0.9 days Standard Deviation 2.0	—
Healthcare Resource Utilization: Number of School and Work Days Missed Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population Number of missed work days	0.6 days Standard Deviation 1.8	0.2 days Standard Deviation 0.7	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: 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.

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.

Outcome measures

Measure	Placebo n=114 Participants 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 n=236 Participants 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).	Dupilumab 200mg q2w 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).
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 Percentage of participants with >=5 missed school days	17.5 percentage of participants	9.7 percentage of participants	—
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 Percentage of participants with >=5 missed work days	7 percentage of participants	0.8 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: 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.

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.

Outcome measures

Measure	Placebo n=84 Participants 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 n=175 Participants 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).	Dupilumab 200mg q2w 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).
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 Percentage of participants with >=5 missed school days	17.9 percentage of participants	8.6 percentage of participants	—
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 Percentage of participants with >=5 missed work days	6 percentage of participants	0.6 percentage of participants	—

SECONDARY outcome

Timeframe: From Baseline up to Week 64

Population: 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.

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.

Outcome measures

Measure	Placebo n=134 Participants 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 n=271 Participants 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).	Dupilumab 200mg q2w 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).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TEAE	107 Participants	225 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TESAE	6 Participants	13 Participants	—

SECONDARY outcome

Timeframe: Baseline, Weeks 6, 12, 24, 52, 64

Population: 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.

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.

Outcome measures

Measure	Placebo n=91 Participants 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 n=179 Participants 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).	Dupilumab 200mg q2w 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).
Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum Baseline	0.00 nanograms per milliliter Geometric Coefficient of Variation 948.683	0.00 nanograms per milliliter Geometric Coefficient of Variation 0.000	—
Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum Week 6	28566.81 nanograms per milliliter Geometric Coefficient of Variation 47.114	50269.81 nanograms per milliliter Geometric Coefficient of Variation 46.667	—
Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum Week 12	37741.97 nanograms per milliliter Geometric Coefficient of Variation 46.516	63476.17 nanograms per milliliter Geometric Coefficient of Variation 44.444	—
Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum Week 24	42283.09 nanograms per milliliter Geometric Coefficient of Variation 47.910	49525.35 nanograms per milliliter Geometric Coefficient of Variation 52.806	—
Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum Week 52	41467.97 nanograms per milliliter Geometric Coefficient of Variation 49.368	45295.35 nanograms per milliliter Geometric Coefficient of Variation 56.990	—
Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum Week 64	39.00 nanograms per milliliter Geometric Coefficient of Variation 0.000	39.00 nanograms per milliliter Geometric Coefficient of Variation 0.000	—

SECONDARY outcome

Timeframe: From Baseline up to Week 64

Population: 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.

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).

Outcome measures

Measure	Placebo n=133 Participants 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 n=91 Participants 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).	Dupilumab 200mg q2w n=178 Participants 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).
Percentage of Participants With Treatment Emergent Antidrug Antibodies (ADA) Response Treatment-emergent ADA	3.0 percentage of participants	4.4 percentage of participants	7.3 percentage of participants
Percentage of Participants With Treatment Emergent Antidrug Antibodies (ADA) Response Treatment-boosted ADA	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline up to Week 64

Population: Analysis was performed on safety population.

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).

Outcome measures

Measure	Placebo n=134 Participants 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 n=271 Participants 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).	Dupilumab 200mg q2w 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).
Percentage of Participants With Seroconversion	62.5 percentage of participants	79.6 percentage of participants	—

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 89 other events

Deaths: 0 deaths

Dupilumab

Serious events: 13 serious events

Other events: 161 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=134 participants at risk 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 n=271 participants at risk 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).
Blood and lymphatic system disorders Eosinophilia	0.00% 0/134 • 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. 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.	0.74% 2/271 • Number of events 2 • 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. 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.
Blood and lymphatic system disorders Immune Thrombocytopenia	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.
Eye disorders Vision Blurred	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Immune system disorders Allergy To Chemicals	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Immune system disorders Anaphylactic Reaction	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.
Immune system disorders Drug Hypersensitivity	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Immune system disorders Milk Allergy	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Infections and infestations Furuncle	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Infections and infestations Gastroenteritis	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.
Infections and infestations Gastrointestinal Viral Infection	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.
Infections and infestations Lymphadenitis Viral	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.
Infections and infestations Parainfluenzae Virus Infection	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.
Infections and infestations Pharyngitis	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Infections and infestations Pneumonia	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Nervous system disorders Headache	0.00% 0/134 • 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. 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.	0.37% 1/271 • Number of events 1 • 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. 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.
Nervous system disorders Partial Seizures	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/134 • 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. 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.	1.5% 4/271 • Number of events 4 • 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. 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.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.75% 1/134 • Number of events 1 • 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. 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.	0.00% 0/271 • 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. 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.

Other adverse events

Measure	Placebo n=134 participants at risk 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 n=271 participants at risk 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).
Blood and lymphatic system disorders Eosinophilia	0.75% 1/134 • Number of events 1 • 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. 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.	5.5% 15/271 • Number of events 15 • 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. 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.
General disorders Injection Site Erythema	9.7% 13/134 • Number of events 93 • 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. 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.	12.9% 35/271 • Number of events 153 • 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. 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.
General disorders Injection Site Oedema	5.2% 7/134 • Number of events 15 • 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. 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.	10.3% 28/271 • Number of events 72 • 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. 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.
Infections and infestations Bronchitis	10.4% 14/134 • Number of events 22 • 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. 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.	6.3% 17/271 • Number of events 21 • 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. 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.
Infections and infestations Influenza	9.0% 12/134 • Number of events 17 • 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. 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.	7.4% 20/271 • Number of events 22 • 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. 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.
Infections and infestations Nasopharyngitis	21.6% 29/134 • Number of events 45 • 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. 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.	18.5% 50/271 • Number of events 76 • 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. 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.
Infections and infestations Pharyngitis	10.4% 14/134 • Number of events 19 • 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. 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.	8.5% 23/271 • Number of events 27 • 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. 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.
Infections and infestations Sinusitis	5.2% 7/134 • Number of events 10 • 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. 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.	3.3% 9/271 • Number of events 11 • 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. 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.
Infections and infestations Upper Respiratory Tract Infection	13.4% 18/134 • Number of events 30 • 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. 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.	12.9% 35/271 • Number of events 59 • 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. 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.
Infections and infestations Viral Upper Respiratory Tract Infection	9.7% 13/134 • Number of events 17 • 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. 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.	12.2% 33/271 • Number of events 41 • 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. 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.
Nervous system disorders Headache	7.5% 10/134 • Number of events 17 • 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. 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.	6.6% 18/271 • Number of events 29 • 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. 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.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 9/134 • Number of events 10 • 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. 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.	5.5% 15/271 • Number of events 17 • 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. 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.
Respiratory, thoracic and mediastinal disorders Rhinitis Allergic	11.9% 16/134 • Number of events 19 • 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. 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.	5.9% 16/271 • Number of events 27 • 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. 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.

Additional Information

Trial Transparency Team

Sanofi

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Results disclosure agreements

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Restriction type: OTHER