Study to Investigate the Efficacy and Safety of Dupilumab Administered With Topical Corticosteroids (TCS) in Participants ≥6 to <12 Years With Severe Atopic Dermatitis (AD)

Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Itch Score ≥3 Points at Week 16

The worst itch scale was a simple assessment tool that participants used to report the intensity of their pruritus (itch). This was an 11-point scale (0 to 10) in which 0 indicated no itching while 10 indicated worst itching possible. Participants were asked to answer 2 questions daily throughout the entire study (screening period, treatment period, and follow-up period). The daily worst itch score was calculated as the worse of the scores for the 2 questions. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Here "Number of participants analyzed" = number of participants who were evaluated for this specific endpoint.

Time frame: Week 16

Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Itch Score ≥4 Points at Week 16

The worst itch scale was a simple assessment tool that participants used to report the intensity of their pruritus (itch). This was an 11-point scale (0 to 10) in which 0 indicated no itching while 10 indicated worst itching possible. Participants were asked to answer 2 questions daily throughout the entire study (screening period, treatment period, and follow-up period). The daily worst itch score was calculated as the worse of the scores for the 2 questions. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Here "Number of participants analyzed" = number of participants who were evaluated for this specific endpoint.

Time frame: Week 16

Percentage of Participants Achieving Eczema Area and Severity Index - 50 (EASI-50) (≥ 50% Improvement From Baseline) at Week 16

The EASI assessed severity and extent of AD. Scores range from 0-72. Four AD disease characteristics (erythema, thickness, scratching, and lichenification) were assessed for severity on a scale of "0" (absent) through "3" (severe). Area of involvement assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder.

Time frame: Week 16

Percentage of Participants Achieving Eczema Area and Severity Index - 90 (EASI - 90) (≥ 90% Improvement From Baseline) at Week 16

The EASI assessed the severity and extent of atopic dermatitis (AD). Scores range from 0-72. Four AD disease characteristics (erythema, thickness, scratching, and lichenification) were assessed for severity on a scale of "0" (absent) through "3" (severe). Area of involvement assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder.

Time frame: Week 16

Time to Achieve ≥ 4 Point Reduction of Weekly Average of Daily Worst Itch Score From Baseline During the 16-week Treatment Period

The worst itch scale: simple assessment tool that participants used to report intensity of their pruritus (itch). This was an 11-point scale (0 to 10) where 0 (no itching) and 10 (worst itching) possible. Participants were asked to answer 2 questions daily throughout the entire study (screening period, treatment period, \& follow-up period). The daily worst itch score was calculated as worse of scores for 2 questions. FAS was used. Time to event is calculated in weeks as (date of first event - date of first dose)/7. The event of NRS reduction ≥ 4 was based on observed data without setting data to be non-responder after rescue treatment use. Here "Number of participants analyzed" = number of participants who were evaluated for this specific endpoint \& "NA" represents "Not computable" as only 12.3% of participants achieved NRS reduction during 16-week treatment period \& hence median time to achieve ≥ 4-point reduction of NRS for placebo +TCS treated participants could not be reported.

Time frame: Baseline (Day 1) up to Week 16

Time to Achieve ≥ 3 Point Reduction of Weekly Average of Daily Worst Itch Score From Baseline During the 16-week Treatment Period

The worst itch scale: a simple assessment tool that participants used to report intensity of their pruritus (itch). This was an 11-point scale (0 to 10) where 0 (no itching) \& 10 (worst itching) possible. Participants were asked to answer 2 questions daily throughout the entire study (screening period, treatment period, \& follow-up period). Daily worst itch score was calculated as worse of scores for 2 questions. FAS was used. Time to event is calculated in weeks as (date of first event - date of first dose)/7. The event of NRS reduction ≥ 3 was based on observed data without setting data to be non-responder after rescue treatment use. Here "Number of participants analyzed" = number of participants who were evaluated for this specific endpoint \& "NA" represents "Not computable" as only 21.1% of participants achieved NRS reduction during 16-week treatment period \& hence median time to achieve ≥ 3-point reduction of NRS for placebo +TCS treated participants could not be reported.

Time frame: Baseline (Day 1) up to Week 16

Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16

BSA affected by AD was assessed for each section of the body using the rule of nines (the possible highest score for each region is: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]) and were reported as a percentage of all major body sections combined. The proportion assigned to different body regions were different in younger children as compared to older children (head and neck area is assigned a higher proportion in younger children as compared to older children). The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Time frame: Baseline (Day 1), Week 16

Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16

SCORAD was used to assess the extent and severity of AD. Extent and severity of eczema as well as subjective symptoms (insomnia, etc) were assessed and scored. SCORAD total score ranges from 0 (absent disease) to 103 (severe disease). The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Time frame: Baseline (Day 1), Week 16

Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16

CDLQI was a validated 10 question tool to measure the impact of skin disease on the quality of life (QOL) in children by assessing how much the skin problem has affected the participant over the past week. Nine questions were scored as follows: Very much = 3, Quite a lot = 2, Only a little = 1, Not at all or unanswered = 0. Question 7 has an added possible response, which was scored as 3. CDLQI equals the sum of the score of each question (maximum = 30, minimum = 0). Higher the score, the greater the impact on QOL. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Data presented reflects the mean \& standard deviation of the CDLQI total scores.

Time frame: Baseline (Day 1), Week 16

Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16

POEM was a 7-item, validated questionnaire used to assess disease symptoms in children and adults. The format was a response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on frequency of these disease symptoms during the past week (ie, 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days) with a scoring system of 0 to 28; the total score reflected the disease-related morbidity. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). A high score is indicative of a poor quality of life.

Time frame: Baseline (Day 1), Week 16

Change From Baseline in Weekly Average of Daily Worst Itch Score at Week 16

The worst itch scale was a simple assessment tool that participants used to report the intensity of their pruritus (itch). This was an 11-point scale (0 to 10) in which 0 indicated no itching while 10 indicated worst itching possible. Participants were asked to answer 2 questions daily throughout the entire study (screening period, treatment period, and follow-up period). The daily worst itch score was calculated as the worse of the scores for the 2 questions. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Time frame: Baseline (Day 1), Week 16

Change From Baseline in Dermatitis Family Index (DFI) at Week 16

DFI was a 10-item questionnaire with items inquiring about housework, food preparation, sleep, family leisure activity, shopping, expenditure, tiredness, emotional distress, relationships and the impact of helping with treatment on the primary caregiver's life. The DFI questions were scored on a four-point Likert scale ranging from 0 to 3, so that the total DFI score ranges from 0 to 30. Timeframe of reference was the past week. A higher DFI score indicated greater impairment in family Quality of life (QOL) as affected by atopic dermatitis. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Time frame: Baseline (Day 1) , Week 16

Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Anxiety Short Form Scale Total Score at Week 16

PROMIS Anxiety instrument measures self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), \& somatic symptoms related to arousal (racing heart, dizziness). Each question has 5 response options ranging in value from 1-5 (1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5=Almost Always). Total raw score calculated using sum of response values: for 8-item form, lowest possible is 8 \& highest possible is 40; For 6-item form: lowest possible is 6; highest possible is 30. Higher score indicates greater severity of symptoms.

Time frame: Baseline (Day 1), Week 16

Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pediatric Depressive Symptoms Short Form Scale Score at Week 16

PROMIS Depression instrument assesses self-reported negative mood (sadness/guilt), views of self (self-criticism/worthlessness) \& social cognition (loneliness/interpersonal alienation), \& decreased positive affect \& engagement (loss of interest/meaning/purpose). Each question has 5 response options with values from 1-5 (1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5=Almost Always). Total raw score is the sum of response values. For 8-item form, lowest possible is 8, highest is 40; for 6-item form, lowest possible is 6, highest is 30. Higher score indicates greater severity of symptoms.

Time frame: Baseline (Day 1), Week 16

Percentage of Participants Having at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infections) Through Week 16

Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-subjects hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Percentage of participants having at least one skin infection TEAE (Excluding Herpetic Infections) through Week 16 were reported. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Time frame: Baseline through Week 16

Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Week 16

Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-participants hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).

Time frame: Baseline (Day 1) through Week 16

Proportion of Topical Corticosteroid (TCS) Medication-free Days From Baseline to Week 16

Proportion of TCS medication-free days is calculated as the number of days that a participant used neither TCS/TCI nor system rescue therapy divided by the study days of each period. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Here "Number of participants analyzed" = number of participants who were evaluated for this specific endpoint.

Time frame: Baseline (Day 1), Week 16

Mean Weekly Dose of Topical Corticosteroid (TCS) in Grams for Low or Medium Potency TCS From Baseline to Week 16

Mean weekly dose of TCS in grams for low or medium potency TCS from baseline to Week 16 were reported. The FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Here "Number of participants analyzed" = number of participants who were evaluated for this specific endpoint.

Time frame: Baseline (Day 1), Week 16