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Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Children 6 to <12 Years of Age with Uncontrolled Persistent Asthma

Summary
EudraCT number	2016-001607-23
Trial protocol	HU LT PL ES Outside EU/EEA IT RO
Global end of trial date	26 Aug 2020

Results information
Results version number	v1(current)
This version publication date	13 Mar 2021
First version publication date	13 Mar 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

EFC14153

ISRCTN number

US NCT number

NCT02948959

WHO universal trial number (UTN)

U1111-1179-4851

Sponsor organisation name

Sanofi aventis recherche & développement

Sponsor organisation address

1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380

Public contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001501-PIP02-13

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

23 Sep 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Aug 2020

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of dupilumab in children 6 to less than (<) 12 years of age with uncontrolled persistent asthma.

Protection of trial subjects

The study was conducted by investigators experienced in the treatment of paediatric patients. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimised. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimise distress and discomfort.

Background therapy

Stable-dose background therapy of medium dose inhaled corticosteroid (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, for at least 3 months with a stable dose greater than or equal to (>=) 1 month prior to screening Visit 1. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication.

Evidence for comparator

Actual start date of recruitment

21 Apr 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 57

Country: Number of subjects enrolled

Australia: 1

Country: Number of subjects enrolled

Brazil: 20

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

Chile: 37

Country: Number of subjects enrolled

Colombia: 8

Country: Number of subjects enrolled

Mexico: 61

Country: Number of subjects enrolled

Russian Federation: 11

Country: Number of subjects enrolled

South Africa: 13

Country: Number of subjects enrolled

Turkey: 11

Country: Number of subjects enrolled

Ukraine: 52

Country: Number of subjects enrolled

United States: 54

Country: Number of subjects enrolled

Hungary: 28

Country: Number of subjects enrolled

Italy: 7

Country: Number of subjects enrolled

Lithuania: 18

Country: Number of subjects enrolled

Poland: 23

Country: Number of subjects enrolled

Spain: 2

Worldwide total number of subjects

408

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

408

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 90 active centres in 17 countries. A total of 631 subjects were screened between 21 April 2017 and 22 July 2019, of which 408 subjects were enrolled and randomised to receive dupilumab or placebo. A total of 223 subjects failed screening mainly due to failure to meet inclusion criteria.

Screening details

Randomisation: stratified by ICS dose level (medium and high), blood eosinophils count (< 0.3 Giga cells/litre [L] and greater than or equal to [>=] 0.3 Giga cells/L), and region (Latin America, Eastern Europe and Western countries). Assignment by Interactive Voice/Web Response System (2:1 ratio) to receive dupilumab/placebo.

Period 1 title

52 Weeks Treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo (for Dupilumab), subcutaneous (SC) injection every 2 weeks (q2w) for 52 weeks in combination with stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/ levosalbutamol was given as reliever medication. Subjects were followed up for 12 weeks after last dose (i.e. up to Week 64).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo (for Dupilumab), SC injection q2w for 52 weeks.

Dupilumab

Arm description

Dupilumab 200 milligrams (mg) (in 1.14 mL for >30 kilograms [kg] bodyweight [BW]) or 100 mg (in 0.67 mL for less than or equal to (<=) 30 kg BW), SC injection q2w for 52 weeks in combination with stable-dose background therapy of medium dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Subjects were followed up for 12 weeks after last dose (i.e. up to Week 64).

Arm type

Experimental

Investigational medicinal product name

Dupilumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

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.

Number of subjects in period 1	Placebo	Dupilumab
Started	135	273
Treated	135	270
Safety Population	134	271
Type 2 Inflammatory Asthma Phenotype	114 ^[1]	236 ^[2]
Baseline Eosinophils Count >=0.3 Giga/L	84 ^[3]	175 ^[4]
Completed	130	248
Not completed	5	25
Randomised and not treated	-	3
Consent withdrawn by subject	2	2
Subject used protocol prohibited vaccine	1	6
Randomised by error	-	5
Adverse Event	2	5
Change of residence location	-	1
Poor compliance to protocol	-	2
Non-compliant to study treatment	-	1

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Randomised subjects with baseline blood eosinophils >=0.15 G iga/L or baseline fractional exhaled nitric oxide (FeNO) >=20 parts per billion (ppb).
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Randomised subjects with baseline blood eosinophils >=0.15 G iga/L or baseline FeNO >=20 ppb.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Randomised subjects with baseline blood eosinophil count >=0 .3 Giga/L.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Randomised subjects with baseline blood eosinophil count >=0 .3 Giga/L.

Period 2 title

12 Weeks Follow-up Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

Yes

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo (for Dupilumab), SC injection q2w for 52 weeks.

Dupilumab

Arm description

Dupilumab 200 milligrams (mg) (in 1.14 mL for >30 kilograms [kg] bodyweight [BW]) or 100 mg (in 0.67 mL for less than or equal to (<=) 30 kg BW), SC injection 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., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Subjects were followed up for 12 weeks after last dose (i.e. up to Week 64).

Arm type

Experimental

Investigational medicinal product name

Dupilumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

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.

Number of subjects in period 2 ^[5]	Placebo	Dupilumab
Started	9	31
Completed	4	19
Not completed	5	12
Consent withdrawn by subject	3	3
Study site closure	1	-
Randomised by error	-	3
Adverse Event	-	2
Change of residence location	-	2
Poor compliance to protocol	1	2

Notes
[5] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only subjects who completed treatment, did not continue to 1-year long-term open-label extension study (LTS14424; 2017-003317-25) entered Period 2 (12-week posttreatment follow-up period).

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

Dupilumab

Reporting group description

Reporting group values	Placebo	Dupilumab	Total
Number of subjects	135	273	408
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	8.9 ( 1.6 )	8.9 ( 1.7 )	-
Gender categorical
Units: Subjects
Female	48	98	146
Male	87	175	262
Race
Units: Subjects
Caucasian/White	118	242	360
Black/of African descent	9	11	20
Asian/Oriental	0	2	2
American Indian or Alaska Native	0	1	1
Other	8	17	25

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

Dupilumab

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

Dupilumab

Reporting group description

Subject analysis set title

Dupilumab 100 mg q2w

Subject analysis set type

Intention-to-treat

Subject analysis set description

Dupilumab 100 mg (in 0.67 mL for <=30 kg BW), SC injection q2w for 52 weeks in combination with stable dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/ salbutamol or levalbuterol/levosalbutamol was given as reliever medication.

Subject analysis set title

Dupilumab 200 mg q2w

Subject analysis set type

Intention-to-treat

Subject analysis set description

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.

Primary: Annualised Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population

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End point title

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

End point description

A severe asthma exacerbation event was defined as a deterioration of asthma during the 52-week treatment period requiring: use of systemic corticosteroids for >=3 days; and/or hospitalisation or emergency room visit because of asthma requiring systemic corticosteroid treatment. Annualised 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 subject-years followed in the 52-week treatment period. Analysis was performed on type 2 inflammatory asthma phenotype population which included the randomised subjects with baseline blood eosinophil count >=150 cells per microlitre or baseline FeNO >=20 ppb.

End point type

Primary

End point timeframe

Baseline to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	114	236
Units: exacerbations per subject-years
number (confidence interval 95%)	0.748 (0.542 to 1.034)	0.305 (0.223 to 0.416)

Dupilumab versus Placebo

Statistical analysis description

Risk ratio and p-value was derived using negative binomial model with total number of events onset from randomisation up to Week 52 visit or last contact date (whichever comes earlier) as response variable, with treatment group, age, baseline weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level and number of severe exacerbation events within 1 year prior to study as covariates and log-transformed standardised observation duration as an offset variable.

Comparison groups

Dupilumab v Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

< 0.0001 ^[2]

Method

Negative binomial model

Parameter type

Risk ratio (RR)

Point estimate

0.407

Confidence interval

level

95%

sides

2-sided

lower limit

0.274

upper limit

0.605

Notes
[1] - To control the type-I error rate for the analysis of outcome measure, a hierarchical testing procedure was applied at a 2-sided 5% significant level. Testing was then performed sequentially in the order endpoints were reported. Hierarchical testing sequence continued only if the previous endpoint was statistically significant. Risk ratio, also called relative risk compares the risk (rate) of an event among one group with the risk (rate) among another group.
[2] - Threshold for statistical significance at 5% significant level.

Primary: Annualised Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Annualised Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

A severe asthma exacerbation event was defined as a deterioration of asthma during the 52-week treatment period requiring: use of systemic corticosteroids for >=3 days; and/or hospitalisation or emergency room visit because of asthma requiring systemic corticosteroid treatment. Annualised 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 subject-years followed in the 52-week treatment period. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population which included the randomised subjects with baseline blood eosinophil count >=300 cells per microlitre.

End point type

Primary

End point timeframe

Baseline to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	84	175
Units: exacerbations per subject-years
number (confidence interval 95%)	0.665 (0.467 to 0.949)	0.235 (0.160 to 0.345)

Dupilumab versus Placebo

Statistical analysis description

Comparison groups

Dupilumab v Placebo

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

< 0.0001 ^[4]

Method

Negative binomial model

Parameter type

Risk ratio (RR)

Point estimate

0.353

Confidence interval

level

95%

sides

2-sided

lower limit

0.222

upper limit

0.562

Notes
[3] - Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant). Risk ratio, also called relative risk compares the risk (rate) of an event among one group with the risk (rate) among another group.
[4] - Threshold for statistical significance at 5% significant level.

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

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End point title

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

End point description

FEV1 was the volume of air 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here,'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline to Week 12

End point values	Placebo	Dupilumab
Number of subjects analysed	110	229
Units: percent predicted FEV1
least squares mean (standard error)	5.32 ( 1.36 )	10.53 ( 1.01 )

Dupilumab versus Placebo

Statistical analysis description

P-value and LS mean difference were derived from MMRM model with change from baseline in pre-bronchodilator % predicted FEV1 value up to Week 12 as the response variable, and treatment, baseline weight group, region, ethnicity, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline % predicted FEV1 value and baseline-by visit interaction as covariates.

Comparison groups

Dupilumab v Placebo

Number of subjects included in analysis

339

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.0009 ^[6]

Method

Mixed-effect model with repeated measure

Parameter type

LS mean difference

Point estimate

5.21

Confidence interval

level

95%

sides

2-sided

lower limit

2.14

upper limit

8.27

Notes
[5] - Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
[6] - Threshold for statistical significance at 5% significant level.

Secondary: Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

FEV1 was the volume of air 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here,'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	Dupilumab
Number of subjects analysed	80	168
Units: percent predicted FEV1
least squares mean (standard error)	4.83 ( 1.54 )	10.15 ( 1.12 )

Dupilumab versus Placebo

Statistical analysis description

Comparison groups

Dupilumab v Placebo

Number of subjects included in analysis

248

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 0.0036 ^[8]

Method

Mixed-effect model with repeated measure

Parameter type

LS mean difference

Point estimate

5.32

Confidence interval

level

95%

sides

2-sided

lower limit

1.76

upper limit

8.88

Notes
[7] - Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
[8] - Threshold for statistical significance at 5% significant level.

Secondary: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Week 24: Type 2 Inflammatory Asthma Phenotype Population

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End point title

Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Week 24: Type 2 Inflammatory Asthma Phenotype Population

End point description

ACQ-7-IA: 7 questions, which assessed: frequency of nocturnal awakenings, severity of asthma symptoms in mornings, limitation of daily activities, shortness of breath due to asthma and wheeze, reliever medication use, and FEV1 (% predicted). Subjects recalled their previous week asthma and answered 5 symptom questions on 7-point scale ranged 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, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, ACQ-7-IA value and baseline-by-visit interaction as covariates. Analysed on type 2 inflammatory asthma phenotype population. 'Number of subjects=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Dupilumab
Number of subjects analysed	110	227
Units: scores on a scale
least squares mean (standard error)	-0.99 ( 0.07 )	-1.32 ( 0.05 )

Dupilumab versus Placebo

Statistical analysis description

P-value and LS mean difference were derived from MMRM model with change from baseline in ACQ-7-IA up to Week 52 as the response variable, and treatment, age, weight group, region, baseline eosinophil level, baseline FeNO level, baseline ICS dose level, visit, treatment by-visit interaction, baseline ACQ-7-IA and baseline-by-visit interaction as covariates.

Comparison groups

Dupilumab v Placebo

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.0001 ^[10]

Method

Mixed-effect model with repeated measure

Parameter type

LS mean difference

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

-0.16

Notes
[9] - Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
[10] - Threshold for statistical significance at 5% significant level.

Secondary: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

ACQ-7-IA: 7 questions, assessed frequency of nocturnal awakenings, severity of asthma symptoms in mornings, limitation of daily activities, shortness of breath due to asthma and wheeze, reliever medication use and FEV1 (% predicted). Subjects recalled previous week asthma and answered 5 symptom questions on 7-point scale ranged 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: 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, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, ACQ-7-IA value and baseline-by-visit interaction as covariates. Analysed on baseline blood eosinophils >=300 cells per microlitre population. 'Number of subjects=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Dupilumab
Number of subjects analysed	80	166
Units: scores on a scale
least squares mean (standard error)	-0.88 ( 0.09 )	-1.34 ( 0.06 )

Dupilumab versus Placebo

Statistical analysis description

Comparison groups

Dupilumab v Placebo

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

< 0.0001 ^[12]

Method

Mixed-effect model with repeated measure

Parameter type

LS mean difference

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.66

upper limit

-0.26

Notes
[11] - Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
[12] - Threshold for statistical significance at 5% significant level.

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

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End point title

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

End point description

FeNO is a surrogate marker for airway inflammation. FeNO was analysed using a NIOX instrument or similar analyser 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	Dupilumab
Number of subjects analysed	110	226
Units: parts per billion
least squares mean (standard error)	-1.13 ( 1.43 )	-18.97 ( 1.04 )

Dupilumab versus Placebo

Statistical analysis description

P-value and LS mean difference were derived from MMRM model with change from baseline in FeNO up to Week 12 as the response variable, and treatment, age, weight group, region, baseline eosinophil level, baseline ICS dose level, visit, treatment by-visit interaction, baseline FeNO value and baseline-by-visit interaction as covariates.

Comparison groups

Dupilumab v Placebo

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

< 0.0001 ^[14]

Method

Mixed-effect model with repeated measure

Parameter type

LS mean difference

Point estimate

-17.84

Confidence interval

level

95%

sides

2-sided

lower limit

-21.05

upper limit

-14.63

Notes
[13] - Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
[14] - Threshold for statistical significance at 5% significant level.

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

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End point title

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

End point description

FeNO is a surrogate marker for airway inflammation. FeNO was analysed using a NIOX instrument or similar analyser 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	Dupilumab
Number of subjects analysed	80	165
Units: parts per billion
least squares mean (standard error)	-0.81 ( 1.69 )	-21.40 ( 1.21 )

Dupilumab versus Placebo

Statistical analysis description

Comparison groups

Dupilumab v Placebo

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

< 0.0001 ^[16]

Method

Mixed-effect model with repeated measure

Parameter type

LS mean difference

Point estimate

-20.59

Confidence interval

level

95%

sides

2-sided

lower limit

-24.6

upper limit

-16.59

Notes
[15] - Testing was performed according to the hierarchical testing procedure (continued only if the previous endpoint was statistically significant).
[16] - Threshold for statistical significance at 5% significant level.

Secondary: 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

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End point title

Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 24, 36 and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

FEV1 was the volume of air (in litres) 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	229
Units: percent predicted FEV1
least squares mean (standard error)
Change at Week 2	4.84 ( 1.29 )	8.11 ( 0.95 )
Change at Week 4	3.55 ( 1.30 )	9.97 ( 0.97 )
Change at Week 8	4.27 ( 1.29 )	10.27 ( 0.96 )
Change at Week 24	4.27 ( 1.40 )	10.92 ( 1.04 )
Change at Week 36	6.63 ( 1.49 )	11.46 ( 1.10 )
Change at Week 52	4.36 ( 1.50 )	12.15 ( 1.10 )

No statistical analyses for this end point

Secondary: 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 Microlitre Population

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End point title

Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 24, 36 and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

FEV1 was the volume of air (in litres) 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	168
Units: percent predicted of FEV1
least squares mean (standard error)
Change at Week 2	3.94 ( 1.51 )	7.49 ( 1.08 )
Change at Week 4	2.19 ( 1.53 )	9.09 ( 1.12 )
Change at Week 8	2.48 ( 1.42 )	9.75 ( 1.04 )
Change at Week 24	3.45 ( 1.63 )	11.10 ( 1.19 )
Change at Week 36	6.87 ( 1.81 )	11.47 ( 1.31 )
Change at Week 52	4.08 ( 1.80 )	12.43 ( 1.30 )

No statistical analyses for this end point

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

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End point title

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

End point description

The time to first severe exacerbation was defined as date of the first severe exacerbation event - randomisation 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 hospitalisation related to asthma symptoms or emergency room visit because of asthma requiring systemic corticosteroid treatment. Kaplan-Meier method was used for analysis. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, '99999' has been used as space filler which indicates that median, upper and lower limit 95% confidence interval (CI) was not estimable due to less than 50% of subjects with events.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	114	236
Units: days
median (confidence interval 95%)	99999 (366.0 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

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

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End point title

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

End point description

The time to first severe exacerbation was defined as date of the first severe exacerbation event - randomisation 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 hospitalisation related to asthma symptoms or emergency room visit because of asthma requiring systemic corticosteroid treatment. Kaplan-Meier method was used for analysis. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, '99999' has been used as space filler which indicates that median, upper and lower limit 95% CI was not estimable due to very low number of subjects with events.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	84	175
Units: days
median (confidence interval 95%)	366.0 (265.00 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	114	236
Units: days
median (confidence interval 95%)	63.5 (42.00 to 84.00)	140.0 (103.00 to 217.00)

No statistical analyses for this end point

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

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End point title

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

End point description

Time to first LOAC event was date of first LOAC event - first dose date +1. A LOAC event was defined as deterioration of asthma during 52-week treatment period that resulted in any of the following: >=6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS dose >=4 times than dose at Visit 2 (Week 0); a decrease in AM/PM peak flow of 30% or more on 2 consecutive days of treatment, based on defined stability limit (defined as respective mean AM/PM peak expiratory flow obtained over last 7 days prior to randomisation (Day 1); severe exacerbation event. Kaplan-Meier method was used for analysis. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population.

End point type

Secondary

End point timeframe

Baseline up to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	84	175
Units: days
median (confidence interval 95%)	47.5 (38.00 to 84.00)	135.0 (82.00 to 219.00)

No statistical analyses for this end point

Secondary: Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

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End point title

Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

FEV1 was the volume of air (in litres) 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	229
Units: litres
least squares mean (standard error)
Change at Week 2	0.08 ( 0.03 )	0.14 ( 0.02 )
Change at Week 4	0.06 ( 0.03 )	0.18 ( 0.02 )
Change at Week 8	0.09 ( 0.03 )	0.21 ( 0.02 )
Change at Week 12	0.12 ( 0.03 )	0.22 ( 0.02 )
Change at Week 24	0.14 ( 0.03 )	0.27 ( 0.02 )
Change at Week 36	0.23 ( 0.03 )	0.33 ( 0.02 )
Change at Week 52	0.24 ( 0.03 )	0.41 ( 0.02 )

No statistical analyses for this end point

Secondary: Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

FEV1 was the volume of air (in litres) 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	168
Units: litres
least squares mean (standard error)
Change at Week 2	0.07 ( 0.03 )	0.13 ( 0.02 )
Change at Week 4	0.04 ( 0.03 )	0.17 ( 0.02 )
Change at Week 8	0.06 ( 0.03 )	0.20 ( 0.02 )
Change at Week 12	0.12 ( 0.03 )	0.22 ( 0.02 )
Change at Week 24	0.13 ( 0.03 )	0.28 ( 0.03 )
Change at Week 36	0.24 ( 0.04 )	0.33 ( 0.03 )
Change at Week 52	0.25 ( 0.04 )	0.42 ( 0.03 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

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End point title

Percent Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	229
Units: percent change
least squares mean (standard error)
Change at Week 2	8.07 ( 2.00 )	13.38 ( 1.47 )
Change at Week 4	6.73 ( 2.10 )	16.01 ( 1.55 )
Change at Week 8	7.68 ( 1.87 )	16.33 ( 1.41 )
Change at Week 12	8.87 ( 2.10 )	16.94 ( 1.56 )
Change at Week 24	7.66 ( 2.12 )	17.61 ( 1.57 )
Change at Week 36	10.88 ( 2.85 )	19.19 ( 2.06 )
Change at Week 52	7.92 ( 2.81 )	20.06 ( 2.03 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Percent Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

FEV1 was the volume of air (in litres) 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	168
Units: percent change
least squares mean (standard error)
Change at Week 2	7.55 ( 2.41 )	12.76 ( 1.73 )
Change at Week 4	5.81 ( 2.57 )	15.20 ( 1.87 )
Change at Week 8	6.09 ( 2.10 )	16.01 ( 1.56 )
Change at Week 12	9.56 ( 2.45 )	17.14 ( 1.79 )
Change at Week 24	7.44 ( 2.54 )	18.09 ( 1.85 )
Change at Week 36	12.15 ( 3.67 )	19.65 ( 2.61 )
Change at Week 52	8.50 ( 3.58 )	20.97 ( 2.54 )

No statistical analyses for this end point

Secondary: 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

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End point title

Change From Baseline in Morning (AM) Peak Expiratory Flow (PEF) at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

The PEF is a subject’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 (litres/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 (litres/minute) value and baseline-by-visit interaction as covariates. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	228
Units: litres/minute
least squares mean (standard error)
Change at Week 2	5.57 ( 2.66 )	6.50 ( 2.00 )
Change at Week 4	7.10 ( 3.31 )	12.81 ( 2.43 )
Change at Week 8	7.37 ( 3.56 )	18.05 ( 2.59 )
Change at Week 12	5.37 ( 3.93 )	19.38 ( 2.85 )
Change at Week 24	8.76 ( 4.53 )	23.32 ( 3.25 )
Change at Week 36	17.70 ( 4.99 )	26.77 ( 3.56 )
Change at Week 52	19.88 ( 5.16 )	31.45 ( 3.69 )

No statistical analyses for this end point

Secondary: 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

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End point title

Change From Baseline in Evening (PM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

The PEF is a subject'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 (litres/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 (litres/minute) value and baseline-by-visit interaction as covariates. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	228
Units: litres/minute
least squares mean (standard error)
Change at Week 2	7.62 ( 2.94 )	10.60 ( 2.20 )
Change at Week 4	6.92 ( 3.42 )	15.23 ( 2.52 )
Change at Week 8	5.52 ( 3.60 )	20.17 ( 2.64 )
Change at Week 12	1.71 ( 3.92 )	19.68 ( 2.85 )
Change at Week 24	3.78 ( 4.61 )	22.75 ( 3.32 )
Change at Week 36	12.55 ( 5.06 )	24.69 ( 3.62 )
Change at Week 52	16.46 ( 5.20 )	28.20 ( 3.73 )

No statistical analyses for this end point

Secondary: 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 Microlitre Population

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End point title

Change From Baseline in Morning (AM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

The PEF is a subject’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 and PM PEF (litres/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 (litres/minute) value and baseline-by-visit interaction as covariates. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	167
Units: litres/minute
least squares mean (standard error)
Change at Week 2	5.85 ( 2.97 )	7.94 ( 2.21 )
Change at Week 4	5.62 ( 3.80 )	11.75 ( 2.76 )
Change at Week 8	5.54 ( 4.09 )	17.32 ( 2.96 )
Change at Week 12	4.77 ( 4.65 )	19.25 ( 3.34 )
Change at Week 24	4.78 ( 5.05 )	23.62 ( 3.61 )
Change at Week 36	14.80 ( 5.77 )	26.78 ( 4.08 )
Change at Week 52	19.75 ( 6.33 )	32.80 ( 4.49 )

No statistical analyses for this end point

Secondary: 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 Microlitre Population

Top of page

End point title

Change From Baseline in Evening (PM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

The PEF is a subject'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 (litres/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 (litres/minute) value and baseline-by-visit interaction as covariates. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	167
Units: litres/minute
least squares mean (standard error)
Change at Week 2	5.64 ( 3.42 )	10.02 ( 2.53 )
Change at Week 4	4.36 ( 3.96 )	13.09 ( 2.89 )
Change at Week 8	0.92 ( 4.05 )	17.51 ( 2.96 )
Change at Week 12	-1.37 ( 4.57 )	17.73 ( 3.30 )
Change at Week 24	-1.37 ( 5.21 )	20.30 ( 3.74 )
Change at Week 36	7.52 ( 6.01 )	23.23 ( 4.26 )
Change at Week 52	14.67 ( 6.39 )	26.60 ( 4.54 )

No statistical analyses for this end point

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

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End point title

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

End point description

FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in litres) that can be forcibly blown out after full inspiration in the upright position, measured in litres. 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	229
Units: litres
least squares mean (standard error)
Change at Week 2	0.07 ( 0.02 )	0.07 ( 0.02 )
Change at Week 4	0.07 ( 0.03 )	0.11 ( 0.02 )
Change at Week 8	0.10 ( 0.02 )	0.13 ( 0.02 )
Change at Week 12	0.12 ( 0.03 )	0.14 ( 0.02 )
Change at Week 24	0.16 ( 0.03 )	0.20 ( 0.02 )
Change at Week 36	0.22 ( 0.03 )	0.28 ( 0.02 )
Change at Week 52	0.27 ( 0.03 )	0.37 ( 0.02 )

No statistical analyses for this end point

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

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End point title

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

End point description

FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in litres) 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	168
Units: litres
least squares mean (standard error)
Change at Week 2	0.07 ( 0.03 )	0.06 ( 0.02 )
Change at Week 4	0.08 ( 0.03 )	0.09 ( 0.02 )
Change at Week 8	0.09 ( 0.03 )	0.13 ( 0.02 )
Change at Week 12	0.13 ( 0.03 )	0.14 ( 0.02 )
Change at Week 24	0.17 ( 0.03 )	0.22 ( 0.03 )
Change at Week 36	0.24 ( 0.04 )	0.28 ( 0.03 )
Change at Week 52	0.29 ( 0.04 )	0.38 ( 0.03 )

No statistical analyses for this end point

Secondary: 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

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End point title

Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

FEF is the amount of air 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 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 FEF25-75% 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	229
Units: litres/second
least squares mean (standard error)
Change at Week 2	0.11 ( 0.05 )	0.28 ( 0.04 )
Change at Week 4	0.07 ( 0.05 )	0.34 ( 0.04 )
Change at Week 8	0.10 ( 0.05 )	0.39 ( 0.04 )
Change at Week 12	0.14 ( 0.05 )	0.41 ( 0.04 )
Change at Week 24	0.16 ( 0.05 )	0.44 ( 0.04 )
Change at Week 36	0.29 ( 0.05 )	0.49 ( 0.04 )
Change at Week 52	0.29 ( 0.06 )	0.60 ( 0.04 )

No statistical analyses for this end point

Secondary: Change From Baseline in Forced Expiratory Flow 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Change From Baseline in Forced Expiratory Flow 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

FEF is the amount of air 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 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 FEF25-75% 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	168
Units: litres/second
least squares mean (standard error)
Change at Week 2	0.07 ( 0.05 )	0.29 ( 0.04 )
Change at Week 4	0.00 ( 0.05 )	0.33 ( 0.04 )
Change at Week 8	0.02 ( 0.06 )	0.40 ( 0.04 )
Change at Week 12	0.10 ( 0.05 )	0.42 ( 0.04 )
Change at Week 24	0.12 ( 0.06 )	0.47 ( 0.04 )
Change at Week 36	0.27 ( 0.06 )	0.51 ( 0.05 )
Change at Week 52	0.26 ( 0.07 )	0.65 ( 0.05 )

No statistical analyses for this end point

Secondary: Change From Baseline in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

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End point title

Change From Baseline in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

Subjects 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 litres) 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	230
Units: litres
least squares mean (standard error)
Change at Week 2	0.61 ( 1.26 )	1.51 ( 0.92 )
Change at Week 4	-0.02 ( 1.15 )	2.42 ( 0.86 )
Change at Week 8	-0.79 ( 1.21 )	2.85 ( 0.90 )
Change at Week 12	-0.32 ( 1.23 )	2.48 ( 0.91 )
Change at Week 24	-0.50 ( 1.31 )	2.60 ( 0.96 )
Change at Week 36	0.55 ( 1.46 )	3.15 ( 1.07 )
Change at Week 52	-0.75 ( 1.48 )	3.62 ( 1.08 )

No statistical analyses for this end point

Secondary: Change From Baseline in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Change From Baseline in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

Subjects 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 litres) 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre opulation. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	169
Units: litres
least squares mean (standard error)
Change at Week 2	0.10 ( 1.49 )	0.52 ( 1.07 )
Change at Week 4	-0.29 ( 1.35 )	1.44 ( 1.00 )
Change at Week 8	-2.05 ( 1.31 )	1.81 ( 0.98 )
Change at Week 12	-0.61 ( 1.44 )	2.28 ( 1.04 )
Change at Week 24	-0.80 ( 1.54 )	2.25 ( 1.12 )
Change at Week 36	0.72 ( 1.80 )	2.87 ( 1.31 )
Change at Week 52	-0.52 ( 1.79 )	3.13 ( 1.30 )

No statistical analyses for this end point

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

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End point title

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

End point description

The morning asthma symptom score: evaluated subject’s overall asthma symptoms experienced during the previous night. It ranged from 0 (no asthma symptoms, slept through night) to 4 (bad night, awake most of night due to 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 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed'=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	228
Units: scores on a scale
least squares mean (standard error)
Change at Week 2	-0.22 ( 0.04 )	-0.18 ( 0.03 )
Change at Week 4	-0.29 ( 0.05 )	-0.34 ( 0.04 )
Change at Week 8	-0.37 ( 0.05 )	-0.39 ( 0.04 )
Change at Week 12	-0.34 ( 0.05 )	-0.48 ( 0.04 )
Change at Week 24	-0.46 ( 0.05 )	-0.56 ( 0.04 )
Change at Week 36	-0.48 ( 0.05 )	-0.56 ( 0.04 )
Change at Week 52	-0.50 ( 0.05 )	-0.61 ( 0.04 )

No statistical analyses for this end point

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

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End point title

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

End point description

The evening asthma symptom score evaluated subject's overall asthma symptom experienced during the day; ranged from 0 (very well, no asthma symptom) to 4(asthma very bad, unable to carry out daily activities as usual), where lower score indicate 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. Analysis was performed on type 2 inflammatory asthma population. 'Number of subjects analysed'=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	228
Units: scores on a scale
least squares mean (standard error)
Change at Week 2	-0.17 ( 0.05 )	-0.13 ( 0.03 )
Change at Week 4	-0.25 ( 0.05 )	-0.29 ( 0.04 )
Change at Week 8	-0.33 ( 0.06 )	-0.40 ( 0.04 )
Change at Week 12	-0.30 ( 0.06 )	-0.45 ( 0.04 )
Change at Week 24	-0.44 ( 0.06 )	-0.53 ( 0.04 )
Change at Week 36	-0.47 ( 0.06 )	-0.55 ( 0.04 )
Change at Week 52	-0.50 ( 0.06 )	-0.59 ( 0.04 )

No statistical analyses for this end point

Secondary: Change From Baseline in Morning (AM) Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Change From Baseline in Morning (AM) Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

The morning asthma symptom score: evaluated subject’s overall asthma symptoms experienced during the previous night. It ranged from 0 (no asthma symptoms, slept through night) to 4 (bad night, awake most of night due to 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 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.Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	167
Units: scores on a scale
least squares mean (standard error)
Change at Week 2	-0.24 ( 0.05 )	-0.20 ( 0.04 )
Change at Week 4	-0.32 ( 0.06 )	-0.34 ( 0.04 )
Change at Week 8	-0.38 ( 0.06 )	-0.40 ( 0.05 )
Change at Week 12	-0.33 ( 0.06 )	-0.48 ( 0.04 )
Change at Week 24	-0.45 ( 0.06 )	-0.55 ( 0.04 )
Change at Week 36	-0.46 ( 0.06 )	-0.56 ( 0.04 )
Change at Week 52	-0.50 ( 0.06 )	-0.62 ( 0.04 )

No statistical analyses for this end point

Secondary: Change From Baseline in Evening (PM) Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Change From Baseline in Evening (PM) Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

The evening asthma symptom score evaluated subject's overall asthma symptom experienced during the day; ranged from 0 (very well, no asthma symptom) to 4(asthma very bad, unable to carry out daily activities as usual), where lower score indicate 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 AS score value and baseline-by-visit interaction as covariates. Analysis was performed on baseline blood eosinophils >=300 cells/microlitre population. 'Number of subjects analysed'=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	167
Units: scores on a scale
least squares mean (standard error)
Change at Week 2	-0.18 ( 0.05 )	-0.15 ( 0.04 )
Change at Week 4	-0.27 ( 0.06 )	-0.29 ( 0.04 )
Change at Week 8	-0.30 ( 0.06 )	-0.41 ( 0.05 )
Change at Week 12	-0.29 ( 0.07 )	-0.48 ( 0.05 )
Change at Week 24	-0.42 ( 0.06 )	-0.53 ( 0.05 )
Change at Week 36	-0.43 ( 0.06 )	-0.56 ( 0.05 )
Change at Week 52	-0.51 ( 0.06 )	-0.60 ( 0.04 )

No statistical analyses for this end point

Secondary: 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

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End point title

Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-question Version (ACQ-5-IA) at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

ACQ-5-IA has 5 questions, reflecting top-scoring 5 asthma symptoms (AS):frequency of nocturnal awakenings, severity of AS in mornings, limitation of daily activities, shortness of breath and wheeze. Subjects recalled their asthma during the previous week; responded to each of 5 symptom questions on 7-point scale ranging from 0 (no impairment) to 6 (maximum impairment). ACQ-5-IA total score: mean of scores of all 5 questions; 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 response variable and treatment, age, baseline: weight group, region, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, ACQ-5-IA value and baseline-by-visit interaction as covariates. Analysed on type 2 inflammatory asthma phenotype population. Here, 'Number of subjects analysed=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	227
Units: scores on a scale
least squares mean (standard error)
Change at Week 2	-0.72 ( 0.09 )	-0.77 ( 0.06 )
Change at Week 4	-0.86 ( 0.08 )	-1.09 ( 0.06 )
Change at Week 8	-1.04 ( 0.09 )	-1.24 ( 0.07 )
Change at Week 12	-1.04 ( 0.08 )	-1.35 ( 0.06 )
Change at Week 24	-1.18 ( 0.08 )	-1.46 ( 0.06 )
Change at Week 36	-1.25 ( 0.08 )	-1.57 ( 0.06 )
Change at Week 52	-1.30 ( 0.07 )	-1.70 ( 0.05 )

No statistical analyses for this end point

Secondary: 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 Microlitre Population

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End point title

Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-question Version at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

ACQ-5-IA: 5 questions, reflecting top-scoring 5 AS: frequency of nocturnal awakenings, severity of AS in mornings, limitation of daily activities, shortness of breath and wheeze. Subjects recalled asthma during the previous week; responded to each of 5 symptom questions on 7-point scale ranging from 0 (no impairment) to 6 (maximum impairment). ACQ-5-IA total score: mean of scores of all 5 questions; 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 response variable and treatment, age, baseline: weight group, region, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, ACQ-5-IA value and baseline-by-visit interaction as covariates. Analysed on baseline blood eosinophils >=300 cells per microlitre population.. Here, 'Number of subjects evaluable=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	166
Units: scores on a scale
least squares mean (standard error)
Change at Week 2	-0.63 ( 0.11 )	-0.76 ( 0.08 )
Change at Week 4	-0.75 ( 0.10 )	-1.10 ( 0.07 )
Change at Week 8	-0.98 ( 0.10 )	-1.27 ( 0.07 )
Change at Week 12	-1.00 ( 0.10 )	-1.37 ( 0.07 )
Change at Week 24	-1.06 ( 0.09 )	-1.48 ( 0.07 )
Change at Week 36	-1.17 ( 0.09 )	-1.59 ( 0.07 )
Change at Week 52	-1.25 ( 0.08 )	-1.71 ( 0.06 )

No statistical analyses for this end point

Secondary: 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

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End point title

Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Weeks 2, 4, 8, 12, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

ACQ-7-IA had 7 questions, assessed: frequency of nocturnal awakenings, severity of asthma symptoms in mornings, limitation of daily activities, shortness of breath due to asthma and wheeze, reliever medication use, and FEV1 (% predicted). Subjects recalled their previous week asthma and answered 5 symptom questions on 7-point scale ranged 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, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, ACQ-7-IA value and baseline-by-visit interaction as covariates. Analysed on type 2 inflammatory asthma phenotype population. 'Number of subjects=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	227
Units: scores on a scale
least squares mean (standard error)
Change at Week 2	-0.60 ( 0.08 )	-0.72 ( 0.06 )
Change at Week 4	-0.74 ( 0.07 )	-1.03 ( 0.05 )
Change at Week 8	-0.91 ( 0.08 )	-1.14 ( 0.06 )
Change at Week 12	-0.89 ( 0.07 )	-1.23 ( 0.05 )
Change at Week 36	-1.09 ( 0.07 )	-1.41 ( 0.05 )
Change at Week 52	-1.09 ( 0.06 )	-1.53 ( 0.05 )

No statistical analyses for this end point

Secondary: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Weeks 2, 4, 8, 12, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Weeks 2, 4, 8, 12, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

ACQ-7-IA:7 questions, assessed frequency of nocturnal awakenings, severity of asthma symptoms in mornings, limitation of daily activities, shortness of breath due to asthma and wheeze, reliever medication use, and FEV1 (% predicted). Subjects recalled previous week asthma and answered 5 symptom questions on 7-point scale ranged 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, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, ACQ-7-IA value and baseline-by-visit interaction as covariates. Analysed on baseline blood eosinophils >=300 cells per microlitre population. 'Number of subjects=subjects evaluable for this endpoint

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	166
Units: scores on a scale
least squares mean (standard error)
Change at Week 2	-0.50 ( 0.09 )	-0.70 ( 0.07 )
Change at Week 4	-0.64 ( 0.09 )	-1.02 ( 0.06 )
Change at Week 8	-0.83 ( 0.09 )	-1.16 ( 0.06 )
Change at Week 12	-0.85 ( 0.09 )	-1.24 ( 0.06 )
Change at Week 36	-1.01 ( 0.08 )	-1.43 ( 0.06 )
Change at Week 52	-1.04 ( 0.08 )	-1.54 ( 0.06 )

No statistical analyses for this end point

Secondary: 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

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End point title

Change From Baseline in Number of Puffs of Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

Subjects might had salbutamol/albuterol or levosalbutamol/levalbuterol as reliever medication. Number of salbutamol/albuterol or levosalbutamol/levalbuterol inhalations recorded daily. In case nebuliser solution used as an alternative delivery method, nebuliser dose converted to number of puffs as per conversion factor: salbutamol/albuterol nebuliser 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 in this endpoint. LS means, SE derived from MMRM. Analysis was performed on Type 2 Inflammatory Asthma Phenotype Population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	228
Units: puffs of reliever medication per 24 hour
least squares mean (standard error)
Change at Week 2	-0.78 ( 0.17 )	-0.65 ( 0.12 )
Change at Week 4	-0.99 ( 0.17 )	-1.02 ( 0.13 )
Change at Week 8	-1.24 ( 0.17 )	-1.28 ( 0.13 )
Change at Week 12	-0.93 ( 0.18 )	-1.41 ( 0.13 )
Change at Week 24	-1.43 ( 0.17 )	-1.61 ( 0.13 )
Change at Week 36	-1.37 ( 0.17 )	-1.60 ( 0.13 )
Change at Week 52	-1.59 ( 0.16 )	-1.72 ( 0.12 )

No statistical analyses for this end point

Secondary: 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 Microlitre Population

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End point title

Change From Baseline in Number of Puffs of Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

Subjects might had salbutamol/albuterol or levosalbutamol/levalbuterol as reliever medication. Number of salbutamol/albuterol or levosalbutamol/levalbuterol inhalations recorded daily. In case nebuliser solution used as an alternative delivery method, nebuliser dose converted to number of puffs as per conversion factor: salbutamol/albuterol nebuliser 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 in this endpoint. LS means, SE derived from MMRM. Analysis was performed on baseline blood eosinophils >=300 cells per microliter population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	167
Units: puffs of reliever medication per 24 hour
least squares mean (standard error)
Change at Week 2	-0.75 ( 0.19 )	-0.67 ( 0.14 )
Change at Week 4	-1.02 ( 0.20 )	-1.01 ( 0.15 )
Change at Week 8	-1.15 ( 0.20 )	-1.29 ( 0.14 )
Change at Week 12	-1.02 ( 0.20 )	-1.39 ( 0.14 )
Change at Week 24	-1.25 ( 0.20 )	-1.53 ( 0.15 )
Change at Week 36	-1.20 ( 0.21 )	-1.49 ( 0.15 )
Change at Week 52	-1.45 ( 0.19 )	-1.58 ( 0.14 )

No statistical analyses for this end point

Secondary: 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

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End point title

Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

Subjects 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. Analysis was performed on type 2 inflammatory asthma phenotype population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	110	228
Units: nocturnal awakenings per night
least squares mean (standard error)
Change at Week 2	-0.13 ( 0.03 )	-0.13 ( 0.02 )
Change at Week 4	-0.16 ( 0.03 )	-0.21 ( 0.03 )
Change at Week 8	-0.21 ( 0.04 )	-0.21 ( 0.03 )
Change at Week 12	-0.17 ( 0.04 )	-0.26 ( 0.03 )
Change at Week 24	-0.23 ( 0.03 )	-0.29 ( 0.02 )
Change at Week 36	-0.25 ( 0.03 )	-0.29 ( 0.02 )
Change at Week 52	-0.26 ( 0.03 )	-0.32 ( 0.02 )

No statistical analyses for this end point

Secondary: 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 Microlitre Population

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End point title

Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

Subjects 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. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. Here, 'number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Dupilumab
Number of subjects analysed	80	167
Units: nocturnal awakenings per night
least squares mean (standard error)
Change at Week 2	-0.15 ( 0.03 )	-0.12 ( 0.02 )
Change at Week 4	-0.19 ( 0.04 )	-0.21 ( 0.03 )
Change at Week 8	-0.22 ( 0.05 )	-0.20 ( 0.04 )
Change at Week 12	-0.16 ( 0.04 )	-0.25 ( 0.03 )
Change at Week 24	-0.21 ( 0.04 )	-0.28 ( 0.03 )
Change at Week 36	-0.25 ( 0.04 )	-0.27 ( 0.03 )
Change at Week 52	-0.26 ( 0.03 )	-0.32 ( 0.02 )

No statistical analyses for this end point

Secondary: Change From Baseline in Paediatric Asthma Quality of Life (QoL) Questionnaire With Standardised Activities-Interviewer Administered (PAQLQ[S] IA) Scores at Weeks 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

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End point title

Change From Baseline in Paediatric Asthma Quality of Life (QoL) Questionnaire With Standardised Activities-Interviewer Administered (PAQLQ[S] IA) Scores at Weeks 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

End point description

PAQLQ(S)-IA is a disease-specific, interviewer-administered QoL questionnaire, measured functional impairments in children >=7 years with asthma. PAQLQ(S)-IA comprises of 23 items (I) in 3 domains: symptoms (10 I), activity limitation (5 I) and emotional function (8 I). Each item was scored on 7-point likert scale (1=maximal impairment to 7=no impairment). 23 items were averaged to give 1 overall QoL score ranged 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 response variable and treatment, age, baseline - weight group, region, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, baseline PAQLQ(S)-IA global score value and baseline-by-visit interaction as covariates. Type 2 inflammatory asthma phenotype population. 'Number of subjects analysed'=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 12, 24, 36, 52

End point values	Placebo	Dupilumab
Number of subjects analysed	102	201
Units: scores on a scale
least squares mean (standard error)
Change at Week 12	0.97 ( 0.09 )	1.08 ( 0.07 )
Change at Week 24	1.11 ( 0.09 )	1.30 ( 0.07 )
Change at Week 36	1.15 ( 0.09 )	1.48 ( 0.07 )
Change at Week 52	1.19 ( 0.08 )	1.53 ( 0.06 )

No statistical analyses for this end point

Secondary: Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities-Interviewer Administered Scores at Weeks 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities-Interviewer Administered Scores at Weeks 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

PAQLQ(S)-IA: disease-specific, interviewer-administered QoL questionnaire, measured functional impairments in children >=7 years with asthma. It comprises of 23 items (I) in 3 domains: symptoms (10 I), activity limitation (5 I) and emotional function (8 I). Each item was scored on 7-point likert scale (1=maximal impairment to 7=no impairment). 23 items were averaged to 1 overall QoL score ranged 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 response variable and treatment, age, baseline - weight group, region, eosinophil level, FeNO level, ICS dose level, visit, treatment by-visit interaction, baseline PAQLQ(S)-IA global score value and baseline-by-visit interaction as covariates. baseline blood eosinophils >=300 cells per microlitre population. 'Number of subjects analysed'=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 12, 24, 36, 52

End point values	Placebo	Dupilumab
Number of subjects analysed	76	149
Units: scores on a scale
least squares mean (standard error)
Change at Week 12	0.90 ( 0.10 )	1.11 ( 0.08 )
Change at Week 24	1.06 ( 0.10 )	1.36 ( 0.08 )
Change at Week 36	1.07 ( 0.10 )	1.51 ( 0.08 )
Change at Week 52	1.23 ( 0.09 )	1.56 ( 0.07 )

No statistical analyses for this end point

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

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End point title

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

End point description

The number of days missed from school by the subject and the number of days missed from work by the caregiver of subject 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 summarised using mean and standard deviation (SD). Analysis was performed on type 2 inflammatory asthma phenotype population. For the caregiver data, population assessed was children subject only and the work days missed by their caregiver were counted.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	114	236
Units: days
arithmetic mean (standard deviation)
Number of missed school days	2.1 ( 4.2 )	1.0 ( 2.3 )
Number of missed work days	0.7 ( 1.9 )	0.2 ( 0.8 )

No statistical analyses for this end point

Secondary: Healthcare Resource Utilisation: Number of School and Work Days Missed Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Healthcare Resource Utilisation: Number of School and Work Days Missed Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

The number of days missed from school by the subject and the number of days missed from work by the caregiver of subject 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 summarised using mean and SD. Analysis was performed on baseline blood eosinophils >=300 cells per microlitre population. For the caregiver data, population assessed was children subject only and the work days missed by their caregiver were counted.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	84	175
Units: days
arithmetic mean (standard deviation)
Number of missed school days	2.0 ( 3.5 )	0.9 ( 2.0 )
Number of missed work days	0.6 ( 1.8 )	0.2 ( 0.7 )

No statistical analyses for this end point

Secondary: Healthcare Resource Utilisation: Percentage of Subjects Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population

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End point title

Healthcare Resource Utilisation: Percentage of Subjects Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population

End point description

The number of days missed from school for the subject and the missed number of days from work for the caregiver due to a LOAC were collected in the eCRF. The percentage of subjects who had at least 5 days (school days and work days) missed due to LOAC over the study period was reported. Analysis was performed on type 2 inflammatory asthma phenotype population.

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	114	236
Units: percentage of subjects
number (not applicable)
Percentage of subjects >=5 school days	17.6	9.8
Percentage of subjects >=5 work days	7	0.8

No statistical analyses for this end point

Secondary: Healthcare Resource Utilisation: Percentage of Subjects Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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End point title

Healthcare Resource Utilisation: Percentage of Subjects Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

End point description

End point type

Secondary

End point timeframe

Baseline to Week 52

End point values	Placebo	Dupilumab
Number of subjects analysed	84	175
Units: percentage of subjects
number (not applicable)
Percentage of subjects >=5 school days	17.9	8.6
Percentage of subjects >=5 work days	6	0.6

No statistical analyses for this end point

Secondary: Number of Subjects With any Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

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End point title

Number of Subjects With any Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

End point description

Adverse event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation subject 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. An SAE was any untoward medical occurrence that at any dose resulted in:death; or life-threatening experience; or required inpatient hospitalisation or prolongation of existing hospitalisation; 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. Analysis was performed on safety population which included all subjects who actually received at least 1 dose or part of a dose of IMP and were analysed according to the actual treatment received.

End point type

Secondary

End point timeframe

From Baseline up to Week 64

End point values	Placebo	Dupilumab
Number of subjects analysed	134	271
Units: subjects
Any TEAE	107	225
TESAE	6	13

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum

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End point title

Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum

End point description

Data for this outcome measure was planned to be collected and analysed separately for dupilumab 100 mg and 200 mg dose and not planned to be collected and analysed for placebo arm. Analysis was performed on the PK population which consisted of all subjects who actually received at least 1 dose or part of a dose of the IMP, analysed according to the treatment actually received with at least one non-missing result for functional dupilumab concentration in serum. Here, 'number analysed'=number of subjects with available data for each specified category.

End point type

Secondary

End point timeframe

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

End point values	Dupilumab 100 mg q2w	Dupilumab 200 mg q2w
Number of subjects analysed	91	179
Units: nanograms per millilitre
geometric mean (geometric coefficient of variation)
Baseline (n = 90, 178)	0.00 ( 948.683 )	0.00 ( 0.000 )
Week 6 (n = 87, 172)	28566.81 ( 47.114 )	50269.81 ( 46.667 )
Week 12 (n = 90, 174)	37741.97 ( 46.516 )	63476.17 ( 44.444 )
Week 24 (n = 90, 173)	42283.09 ( 47.910 )	49525.35 ( 52.806 )
Week 52 (n = 86, 171)	41467.97 ( 49.368 )	45295.35 ( 56.990 )
Week 64 (n = 4, 15)	39.00 ( 0.000 )	39.00 ( 0.000 )

No statistical analyses for this end point

Secondary: Percentage of Subjects With Treatment-emergent Antidrug Antibodies (ADA) Response

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End point title

Percentage of Subjects With Treatment-emergent Antidrug Antibodies (ADA) Response ^[17]

End point description

ADA response was categorised as: treatment emergent and treatment boosted response. 1) Treatment emergent was defined as an ADA positive response in assay post first dose, when baseline results were negative or missing. 2) Treatment boosted was defined as: an ADA positive response in 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). Analysis was performed on ADA population which consisted of all subjects who actually received at least 1 dose or part of a dose of the IMP, analysed according to treatment actually received and had at least one non-missing ADA result (either ADA negative or ADA positive) in the ADA assay after first dose of IMP. Data for this outcome measure was planned to be collected and analysed separately for dupilumab 100 mg and 200 mg dose.

End point type

Secondary

End point timeframe

From Baseline up to Week 64

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this endpoint was planned to be collected and analysed separately for dupilumab 100 mg and 200 mg dose and not planned to be collected and analysed for overall dupilumab arm.

End point values	Placebo	Dupilumab 100 mg q2w	Dupilumab 200 mg q2w
Number of subjects analysed	133	91	178
Units: percentage of subjects
number (not applicable)
Treatment-emergent ADA	3.0	4.4	7.3
Treatment-boosted ADA	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Seroconversion

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End point title

Percentage of Subjects With Seroconversion

End point description

Seroconversion was defined as a post-vaccination titer >=40 (1/dilution) for those with a pre-vaccination titer <10 (1/dilution), or a >=4-fold increase in post-vaccination titer for those with a pre-vaccination titer >=10 (1/dilution). Analysis was performed on safety population.

End point type

Secondary

End point timeframe

Baseline, Weeks 24 and 52

End point values	Placebo	Dupilumab
Number of subjects analysed	134	271
Units: percentage of subjects
number (not applicable)	62.5	79.6

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All AEs were collected from signature of the informed consent form up to end of post-treatment period (i.e., up to Week 64) regardless of seriousness or relationship to IMP.

Adverse event reporting additional description

Reported AEs were treatment emergent AEs that developed/worsened in grade or became serious 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.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Dupilumab

Reporting group description

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. Subjects were followed up for 12 weeks after last dose (i.e. up to Week 64).

Reporting group title

Placebo

Reporting group description

Placebo (for Dupilumab), SC injection q2w for 52 weeks in combination with stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Subjects were followed up for 12 weeks after last dose (i.e. up to Week 64).

Serious adverse events	Dupilumab	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	13 / 271 (4.80%)	6 / 134 (4.48%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Hand Fracture
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Headache
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Partial Seizures
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Eosinophilia
subjects affected / exposed	2 / 271 (0.74%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Immune Thrombocytopenia
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Allergy To Chemicals
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anaphylactic Reaction
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Drug Hypersensitivity
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Milk Allergy
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Vision Blurred
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	4 / 271 (1.48%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Furuncle
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal Viral Infection
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenitis Viral
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Parainfluenzae Virus Infection
subjects affected / exposed	0 / 271 (0.00%)	1 / 134 (0.75%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 271 (0.37%)	0 / 134 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Dupilumab	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	161 / 271 (59.41%)	89 / 134 (66.42%)
Nervous system disorders
Headache
subjects affected / exposed	18 / 271 (6.64%)	10 / 134 (7.46%)
occurrences all number	29	17
Blood and lymphatic system disorders
Eosinophilia
subjects affected / exposed	15 / 271 (5.54%)	1 / 134 (0.75%)
occurrences all number	15	1
General disorders and administration site conditions
Injection Site Erythema
subjects affected / exposed	35 / 271 (12.92%)	13 / 134 (9.70%)
occurrences all number	153	93
Injection Site Oedema
subjects affected / exposed	28 / 271 (10.33%)	7 / 134 (5.22%)
occurrences all number	72	15
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	15 / 271 (5.54%)	9 / 134 (6.72%)
occurrences all number	17	10
Rhinitis Allergic
subjects affected / exposed	16 / 271 (5.90%)	16 / 134 (11.94%)
occurrences all number	27	19
Infections and infestations
Bronchitis
subjects affected / exposed	17 / 271 (6.27%)	14 / 134 (10.45%)
occurrences all number	21	22
Influenza
subjects affected / exposed	20 / 271 (7.38%)	12 / 134 (8.96%)
occurrences all number	22	17
Nasopharyngitis
subjects affected / exposed	50 / 271 (18.45%)	29 / 134 (21.64%)
occurrences all number	76	45
Pharyngitis
subjects affected / exposed	23 / 271 (8.49%)	14 / 134 (10.45%)
occurrences all number	27	19
Sinusitis
subjects affected / exposed	9 / 271 (3.32%)	7 / 134 (5.22%)
occurrences all number	11	10
Upper Respiratory Tract Infection
subjects affected / exposed	35 / 271 (12.92%)	18 / 134 (13.43%)
occurrences all number	59	30
Viral Upper Respiratory Tract Infection
subjects affected / exposed	33 / 271 (12.18%)	13 / 134 (9.70%)
occurrences all number	41	17

More information

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Were there any global substantial amendments to the protocol? Yes

10 Mar 2017

• FeNO results were not blinded to Investigators or site personnel. • Exclusion criterion - to clearly define the interval between live (attenuated) vaccines administration and IMP administration and be consistent with other dupilumab trials. • To correct the description of PAQLQ domains and PAQLQ(S)-IA periodicity. • To correct the values for medium and high dose of beclometasone dipropionate (chlorofluorocarbon and hydrofluoroalkane) and budesonide (dry powder inhaler). • Clarification of PEF meter. • To add IMP compliance check. • To clarify that a separate informed assent form had to be obtained from female subjects who started menstruating • Clarification of subject monitoring. • Clarification of PK sample blood volume for paediatric study. • Clarification of vaccination response. • To remove suicidal behavior from the list of AEs of special interests.

18 Jun 2018

• To increase the sample size due to an update on the assumptions based on the concluded Phase 3 dupilumab clinical trial in adult and adolescent subjects with asthma. • Clarification of an inclusion criterion: reversibility attempts definition during the screening period. • To include new countries/sites in the trial. • Change in schedule of collection of blood samples: change of last possible date for post vaccination sample collection from Week 48 to Week 50. • Clarification that potent dermatological topical corticosteroids were prohibited concomitant medications. • Removal of using prior assessments for re-screening. • To include reliever medication baseline definition. • Change of safety monitoring parameter: to adjust the neutrophil count defining neutropenia (<1000/cubic millimetre) in the study population age group (paediatric trial).

18 Oct 2019

• To change the study primary efficacy analysis population from an overall uncontrolled persistent asthma population to the population with evidence of either asthma with baseline eosinophil count >=0.3 Giga/L or, more broadly, asthma with the type 2 inflammatory asthma phenotype. • To change the sample size. • To specify the different hierarchy orders used for the United States (US) and US reference countries and European Union (EU) countries and EU reference countries. • Removal of the limit in enrolling subjects according to background therapy with medium dose ICS or blood eosinophil count level. • To describe the planned database lock. • To classify FeNO as a secondary endpoint instead of an exploratory endpoint. • To describe the fasting status. • To allow for home dosing start after Visit 9. • To clarify that ACQ-5 data collected on Visit 2 can be used for inclusion criterion. • To clarify how ACQ-7 value was calculated for statistical analysis. • To clarify deoxyribonucleic acid sample collection timeline. • To remove a sentence on the possible hurdle to public health value of the study in case of study withdrawal.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Children 6 to <12 Years of Age with Uncontrolled Persistent Asthma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Annualised Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population

Primary: Annualised Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population

Primary: Annualised Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Primary: Annualised Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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

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

Secondary: Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Week 24: Type 2 Inflammatory Asthma Phenotype Population

Secondary: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Week 24: Type 2 Inflammatory Asthma Phenotype Population

Secondary: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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

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

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

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

Secondary: 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

Secondary: 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

Secondary: 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 Microlitre Population

Secondary: 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 Microlitre Population

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

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

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

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

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

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

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

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

Secondary: Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

Secondary: Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

Secondary: Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Percent Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

Secondary: Percent Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population

Secondary: Percent Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Percent Change From Baseline in Pre-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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 Microlitre Population

Secondary: 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 Microlitre Population

Secondary: 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 Microlitre Population

Secondary: 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 Microlitre Population

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

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

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

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

Secondary: 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

Secondary: 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

Secondary: Change From Baseline in Forced Expiratory Flow 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Forced Expiratory Flow 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

Secondary: Change From Baseline in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population

Secondary: Change From Baseline in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Post-Bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

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

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

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

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

Secondary: Change From Baseline in Morning (AM) Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Morning (AM) Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Evening (PM) Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: Change From Baseline in Evening (PM) Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microlitre Population

Secondary: 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

Secondary: 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

Secondary: 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 Microlitre Population

Secondary: 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 Microlitre Population

Secondary: 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

Secondary: 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

Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Children 6 to <12 Years of Age with Uncontrolled Persistent Asthma