A Study to Determine the Safety and Tolerability of Dupil... | NCT02407756

Name	Class
Sanofi	INDUSTRY

Label	Type	Description	Intervention Names
Cohort 1	Experimental	Cohort 1 will receive dupilumab dosing regimen 1	Drug: Dupilumab
Cohort 2	Experimental	Cohort 2 will receive dupilumab dosing regimen 2	Drug: Dupilumab

Name	Type	Description	Arm Group Labels	Other Names
Dupilumab	Drug		Cohort 1 Cohort 2	REGN668(SAR231893)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pharmacokinetics (PK) of Dupilumab: Maximum Plasma Concentration Observed (Cmax) After Single Administration	Peak dupilumab concentration in serum following single dose administration. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug.	Day 2, 4, 8, 15, 22, 29, 36, 43, and 50
PK of Dupilumab: Area Under the Plasma Concentration Versus Time Curve (AUClast) After Single Administration	Mean AUC estimates were calculated using mean concentration data at each time point, using a non-compartmental approach (NCA). Calculated AUClast (computed from time zero to the time of the last positive concentration) are presented. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug.	Day 2, 4, 8, 15, 22, 29, 36, 43, and 50
PK of Dupilumab: Trough Dupilumab Concentration in Serum (Ctrough) Before 3rd and 4th Repeated Dose	Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of study drug.	Pre-dose on Day 71 and Day 85

Secondary Outcomes

Measure	Description	Time Frame
Percent Reduction From Baseline in Eczema Area and Severity Index (EASI) at Week 12	The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 to 72 points, with the higher scores reflecting the worse severity of AD. Analysis was performed on safety analysis set (SAF) that included all subjects who received any study drug. Data after rescue treatment use during the Part B period were set to missing, then missing values were imputed by last observation carried forward (LOCF).

Eligibility Module

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

PubMed Identifier	Type	Citation	Retractions
35567671	Derived	Blauvelt A, Guttman-Yassky E, Paller AS, Simpson EL, Cork MJ, Weisman J, Browning J, Soong W, Sun X, Chen Z, Kosloski MP, Kamal MA, Delevry D, Chuang CC, O'Malley JT, Bansal A. Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE). Am J Clin Dermatol. 2022 May;23(3):365-383. doi: 10.1007/s40257-022-00683-2. Epub 2022 May 14.
31595499

ID	Title	Description
FG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
FG001	Dupilumab 2mg/kg: Children

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00014.7± 2.01 BG0018.2± 1.62 BG00214.3± 1.66 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00011 BG0019 BG002

Ethnicity

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG00017 BG00117 BG002

Number of Subjects with Investigator Global Assessment (IGA) score of 3 or 4

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/ infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Analysis was performed on SAF.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
IGA score of 3	BG0008 BG001

Eczema Area and Severity Index (EASI) score

Mean

Standard Deviation

Score on a scale

Title

Denominators

Categories

Title	Measurements
	BG00034.8± 17 BG001

Pruritus Numerical Rating Scale (NRS)

Pruritus NRS scale is an assessment tool that is used to report the intensity of subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Weekly average obtained in the 7-day period prior to the baseline visit. Analysis was performed on SAF.

Mean

Standard Deviation

Score on a scale

Title

Denominators

Categories

Title	Measurements
	BG0006.1± 2.47 BG001

Body Surface Area (BSA) Involvement with Atopic Dermatitis (AD)

BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined. Analysis was performed on SAF.

Mean

Standard Deviation

Percentage of body surface area

Title

Denominators

Categories

Title	Measurements
	BG00052.2± 24.78 BG001

SCORing Atopic Dermatitis (SCORAD) Score

SCORAD is a clinical tool for assessing the severity of atopic dermatitis developed by the European Task Force on Atopic Dermatitis ("Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis". Dermatology (Basel) 186 (1): 23-31. 1993). Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 [absent disease] to 103 [severe disease]). Analysis was performed on SAF.

Mean

Standard Deviation

Score on a scale

Title

Denominators

Categories

Title	Measurements
	BG00068± 13.19 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Pharmacokinetics (PK) of Dupilumab: Maximum Plasma Concentration Observed (Cmax) After Single Administration

Peak dupilumab concentration in serum following single dose administration. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug.

Posted

Mean

Standard Deviation

mg/L

Day 2, 4, 8, 15, 22, 29, 36, 43, and 50

ID	Title	Description
OG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
OG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG003	Dupilumab 4mg/kg: Children	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.

Units	Counts
Participants	OG00020 OG00118 OG00220 OG003

Title

Denominators

Categories

Title	Measurements
	OG0009.91± 2.15(2.15 to ) OG00114.3± 5.9(5.9 to ) OG00223.1± 8.71(8.71 to )

Primary

PK of Dupilumab: Area Under the Plasma Concentration Versus Time Curve (AUClast) After Single Administration

Mean AUC estimates were calculated using mean concentration data at each time point, using a non-compartmental approach (NCA). Calculated AUClast (computed from time zero to the time of the last positive concentration) are presented. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug.

Posted

Mean

Standard Deviation

Day*mg/L

Day 2, 4, 8, 15, 22, 29, 36, 43, and 50

ID	Title	Description
OG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
OG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.

Primary

PK of Dupilumab: Trough Dupilumab Concentration in Serum (Ctrough) Before 3rd and 4th Repeated Dose

Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of study drug.

Posted

Mean

Standard Deviation

mg/L

Pre-dose on Day 71 and Day 85

ID	Title	Description
OG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
OG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG003	Dupilumab 4mg/kg: Children

Secondary

Percent Reduction From Baseline in Eczema Area and Severity Index (EASI) at Week 12

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 to 72 points, with the higher scores reflecting the worse severity of AD. Analysis was performed on safety analysis set (SAF) that included all subjects who received any study drug. Data after rescue treatment use during the Part B period were set to missing, then missing values were imputed by last observation carried forward (LOCF).

Posted

Mean

Standard Deviation

percent change

Baseline to Week 12 (one week after last dose)

ID	Title	Description
OG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
OG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.

Secondary

Percent Reduction From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 12

Posted

Mean

Standard Deviation

percent change

Baseline to Week 12 (one week after last dose)

ID	Title	Description
OG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
OG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.

Secondary

Percent Reduction From Baseline in Pruritus Numerical Rating Scale (NRS) at Week 12

Pruritus NRS scale is an assessment tool that is used to report the intensity of subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). Analysis was performed on SAF. Data after rescue treatment use during the Part B period were set to missing, then missing values were imputed by LOCF.

Posted

Mean

Standard Deviation

Percent change

Baseline to Week 12 (one week after last dose)

ID	Title	Description
OG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
OG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.

Secondary

Percentage of Subjects With Investigator Global Assessment (IGA) Score of "0" or "1" (Clear or Almost Clear) at Week 12

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Analysis was performed on SAF. Subjects with rescue treatment usage during the Part B period were specified as non-responders from the time the rescue was used.

Posted

Number

Percentage of subjects

Week 12

ID	Title	Description
OG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
OG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.

Secondary

Percent Reduction From Baseline in Body Surface Area (BSA) at Week 12

Body surface area affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]). It was reported as a percentage of all major body sections combined. Analysis was performed on SAF.

Here "Number of participants analyzed" = number of participants who were evaluated for this specific outcome measure.

Posted

Mean

Standard Deviation

Percentage of body surface area

Baseline to Week 12

ID	Title	Description
OG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
OG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
OG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG0030 events0 affected19 at risk
Cyanosis	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Eosinophilia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Conjunctivitis allergic	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Dermoid cyst	Congenital, familial and genetic disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Aphthous stomatitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0022 events2 affected20 at risk EG003
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0022 events1 affected20 at risk EG003
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0022 events2 affected20 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0004 events2 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Injection site urticaria	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Injection site swelling	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Injection site irritation	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Injection site erythema	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Feeling of body temperature change	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Food allergy	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Bacterial disease carrier	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Acute tonsillitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Allergic oedema	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Croup infectious	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Dermatitis infected	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0024 events2 affected20 at risk EG003
Ear infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Folliculitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Gingivitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Herpes simplex	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0023 events1 affected20 at risk EG003
Molluscum contagiosum	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Influenza	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Laryngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Herpes virus infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 events2 affected20 at risk EG0019 events5 affected18 at risk EG00211 events8 affected20 at risk EG003
Oral herpes	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Rhinitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Pharyngitis bacterial	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Paronychia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Skin bacterial infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Skin candida	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected18 at risk EG0021 events1 affected20 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Animal bite	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Bone contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Muscle strain	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Post procedural inflammation	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Protein urine present	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Epiphysiolysis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Akathisia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0022 events1 affected20 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 events1 affected20 at risk EG0011 events1 affected18 at risk EG0021 events1 affected20 at risk EG003
Lethargy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Depressed mood	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events1 affected18 at risk EG0022 events1 affected20 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0022 events1 affected20 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Nasal disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Alopecia areata	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected20 at risk EG00111 events5 affected18 at risk EG0026 events3 affected20 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0022 events1 affected20 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Skin erosion	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Solar dermatitis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected20 at risk EG003
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Markham	Ontario		Canada

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D003872	Dermatitis
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D017443	Skin Diseases, Eczematous
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description
BG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
BG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
BG002	Dupilumab 4mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.
BG003	Dupilumab 4mg/kg: Children	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dupilumab 2mg/kg: Adolescents	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period, then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.	20	1	20	11	20
EG001	Dupilumab 2mg/kg: Children	Dupilumab 2 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period, then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.	18	0	18	11	18
EG002	Dupilumab 4 mg/kg: Adolescents	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period, then 4 repeated doses weekly in subjects aged between ≥12 to <18 years.	20	1	20	16	20
EG003	Dupilumab 4 mg/kg: Children	Dupilumab 4 mg/kg as a single dose on Day 1 followed by 8-week PK sampling period), then 4 repeated doses weekly in subjects aged between ≥6 to <12 years.	19	2	19	18	19

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG0030 events0 affected19 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Staphylococcal skin infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected20 at risk EG003
Dermatitis infected	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected20 at risk EG003