A Study of Baricitinib (LY3009104) in Children and Adolescents With Atopic Dermatitis

Phase 3

Active, not recruiting

Conditions: Atopic Dermatitis

Interventions: Drug: Placebo
Drug: Baricitinib
Drug: Topical corticosteroid

Registration Number: NCT03952559

Lead Sponsor: Eli Lilly and Company

Brief Summary: The reason for this study is to see if the study drug called baricitinib works and is safe in children and teenage participants with atopic dermatitis.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 516

Inclusion Criteria

At or above the 5th percentile of weight for age.
Have been diagnosed with moderate to severe atopic dermatitis for at least 12 months (if 6 years old or older) or at least 6 months (if 2 up to 6 years old).
Have had inadequate response or intolerance to existing topical (applied to the skin) medications within 6 months preceding screening.
Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period).
Agree to use emollients daily.

Exclusion Criteria

Are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus), or a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections.
A history of eczema herpeticum within 12 months, and/or a history of 2 or more episode of eczema herpeticum in the past.
Participants who are currently experiencing a skin infection that requires treatment, or is currently being treated, with topical or systemic antibiotics.
Have any serious illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).
Have been treated with the following therapies:
- Monoclonal antibody for less than 5 half-lives prior to beginning study treatment.
- Received prior treatment with any oral Janus kinase (JAK) inhibitor.
- Received any parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned initiation of study drug or are anticipated to require parenteral injection of corticosteroids during the study.
Have had an intra-articular corticosteroid injection within 2 weeks prior to study entry or within 6 weeks prior to planned initiation of study drug.
Have high blood pressure characterized by a repeated systolic or diastolic blood pressure >95th percentile based on age, sex and height.
Have had major surgery within the past eight weeks or are planning major surgery during the study.
Have experienced any of the following within 12 weeks of screening: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
Have a history of VTE or are considered at high risk of VTE as deemed by the investigator.
Have a history or presence of cardiovascular, respiratory, hepatic, chronic liver disease gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness.
Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection including herpes zoster (shingles or chicken pox), tuberculosis.
Have specific laboratory abnormalities.
Have received certain treatments that are contraindicated.
Pregnant or breastfeeding.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Baricitinib High Dose	Topical corticosteroid	Participants 10 to \< 18 years received Baricitinib high dose (4 mg) and placebo to maintain the blind, administered orally in tablet form QD. Participants 2 to \< 10 years received Baricitinib high dose (2 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
Baricitinib Low Dose	Topical corticosteroid	Participants 10 to \< 18 years received Baricitinib low dose (1 mg) and placebo to maintain the blind, administered orally in tablet form QD. Participants 2 to \< 10 years received Baricitinib low dose (0.5 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
Baricitinib Medium Dose	Topical corticosteroid	Participants 10 to \< 18 years received Baricitinib low dose (1 mg) and placebo to maintain the blind, administered orally in tablet form QD. Participants 2 to \< 10 years received Baricitinib low dose (0.5 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
Placebo	Topical corticosteroid	Participants 10 to \< 18 years received placebo tablets. Participants 2 to \< 10 years received placebo as oral suspension.
Baricitinib Open Label High Dose (PK Lead-in)	Topical corticosteroid	Participants 10 to \< 18 years received Baricitinib high dose (4 mg) administered orally in tablet form QD. Participants 2 to \< 10 years received Baricitinib high dose (2 mg) administered as oral suspension (1 mL) QD.
Placebo	Placebo	Participants 10 to \< 18 years received placebo tablets. Participants 2 to \< 10 years received placebo as oral suspension.
Baricitinib Open Label High Dose (PK Lead-in)	Baricitinib	Participants 10 to \< 18 years received Baricitinib high dose (4 mg) administered orally in tablet form QD. Participants 2 to \< 10 years received Baricitinib high dose (2 mg) administered as oral suspension (1 mL) QD.
Baricitinib High Dose	Baricitinib	Participants 10 to \< 18 years received Baricitinib high dose (4 mg) and placebo to maintain the blind, administered orally in tablet form QD. Participants 2 to \< 10 years received Baricitinib high dose (2 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
Baricitinib Medium Dose	Baricitinib	Participants 10 to \< 18 years received Baricitinib low dose (1 mg) and placebo to maintain the blind, administered orally in tablet form QD. Participants 2 to \< 10 years received Baricitinib low dose (0.5 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
Baricitinib Low Dose	Baricitinib	Participants 10 to \< 18 years received Baricitinib low dose (1 mg) and placebo to maintain the blind, administered orally in tablet form QD. Participants 2 to \< 10 years received Baricitinib low dose (0.5 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.

Primary Outcome Measures

Name	Time	Method
Open Label Pop PK: Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of LY3009104	Predose; 0.25 h; 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose	Open label Pop PK: AUCtau,ss was derived by a population pharmacokinetics approach.
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥2 Point Improvement	Week 16	Percentage of participants achieving IGA of 0 or 1 with a ≥2 point improvement is presented. The IGA measures the investigator's global assessment of the participant's overall severity of their Atopic Dermatitis, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Open Label Population Pharmacokinetics (Pop PK): Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY3009104	Predose; 0.25 hours (h); 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose	Open label Pop PK: Cmax,ss was derived by a population pharmacokinetics approach.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving IGA of 0	Week 16	The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Change From Baseline in Itch NRS for Participants 10 to <18 Years at Study Entry	Baseline, Week 16	The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LS Means were calculated using mixed model repeated measures (MMRM) model includes treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) for Participants 10 to <18 Years Old at Study Entry	Week 16	The Itch Numeric Rating Scale (NRS) is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.
Percentage of Participants Achieving EASI50	Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in EASI score.
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	Week 16	Percentage of participants developing skin infections requiring antibiotic treatment
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)	Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. The results were analyzed using non-responder imputation (NRI). All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as EASI75.
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)	Week 16	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with visual analog scale (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.
Change From Baseline in SCORAD	Baseline, Week 16	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in Body Surface Area (BSA) Affected	Baseline, Week 16	Body surface area affected by atopic dermatitis will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of atopic dermatitis. LS Means calculated using MMRM model with treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Percentage of Participants Achieving EASI90	Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score. The results were analyzed using non-responder imputation (NRI). All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as EASI90.
Mean Number of Days Without Use of Background Topical Corticosteroid (TCS)	Baseline Through 16 Weeks	Mean number of days without use of background TCS was presented. The ANOVA model includes treatment, age cohort, region, and baseline disease severity (IGA) as factors.
Change From Baseline in EASI Score	Baseline, Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs (1) erythema (2)edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score is obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). Least Square (LS) Means were calculated using a mixed model repeated measures (MMRM) model with treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Percentage of Participants Achieving SCORAD90	Week 16	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. SCORAD90 is defined as a ≥ 90% improvement from baseline in the SCORAD score.
Change From Baseline on the Patient-Oriented Eczema Measure (POEM) Total Score	Baseline, Week 16	The POEM is a simple, 7-item, patient-administered scale that assesses disease severity in children and adults. Participants respond to questions about the frequency of 7 symptoms (itching, sleep disturbance, bleeding, weeping/oozing, cracking, flaking, and dryness/roughness) over the last week on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). Scores range from 0-28 with higher total scores indicating greater disease severity. LS Means were calculated using MMRM model includes treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in the PROMIS-Pediatric Anxiety for Participants 5 to <18 Years at Study Entry	Baseline, Week 16	PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. The PROMIS Anxiety item bank assesses self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). The PROMIS Anxiety Short Form (8 questions, 8a v2.0) is available in a pediatric self-report (ages 8 to \<18 years) and for parents/caregivers serving as proxy reporters for their children (youth ages 5 to \<8 years old). Children aged \<5 years will not complete this assessment. Both pediatric self-report and proxy-report versions assess anxiety "in the past seven days." Response options range from 1= Never; 2 = Rarely; 3 = Sometimes; 4 = Often; to 5 = Almost always. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety.
Change From Baseline in Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score for Participants 10 to <18 Years at Study Entry	Baseline, Week 16	The PGI-S-AD is a single-item question asked to the participants on how they would rate their overall atopic dermatitis symptoms over the past 24 hours to evaluate the severity of the disease at that point in time. The 5 categories of responses range from "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe". LS Means were calculated using mixed model repeated measures (MMRM) model includes treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Pop PK: Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of LY3009104	Predose; 0.25 hours (h); 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose	Pop PK: AUCtau,ss was derived by a population pharmacokinetics approach.
Mean Gram Quantity of TCS Use (Tube Weights)	Baseline through 16 Weeks	The dispensed TCS tubes were weighed with cap (without the carton) to determine the dispensed amount of TCS in grams. Returned tubes were weighed with cap (without the carton) to determine the amount of TCS in grams used at each visit. Analysis was done via analysis of variance (ANOVA), with geographic region, baseline disease severity, and treatment as factors in the model.
Change From Baseline in the Parent-Reported Itch Severity Measure (PRISM) for Participants 2 to <10 Years at Study Entry	Baseline, Week 16	The Parent-Reported Itch Severity Measure (PRISM) is a single-item, parent/caregiver administered scale that reports the overall severity of their child's itching. Parent/Caregiver's report the overall severity of their child's itching based on observed actions of the child in the past 24 hours. Response options range include "No Itch," "Mild," "Moderate," "Severe," and "Very Severe." The PRISM will be completed for participants \<10 years old by the parent/caregiver. LS Means were calculated using mixed model repeated measures (MMRM) model includes treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) at Week 16 for Participants 4 to <18 Years at Study Entry	Baseline, Week 16	CDLQI is a validated 10 question tool to measure impact of skin disease on QOL in children by assessing how much the skin problem has affected the subjects over 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 (max. = 30, min. = 0). Higher the score, the greater the impact on QOL. A negative change from baseline indicated improvement. LS Means were calculated using mixed model repeated measures (MMRM) model includes treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change of Immunoglobulin G (IgG) Titers	Baseline Through End of Study Completion	Number of participants with change of IgG titers for tetanus vaccine and pneumococcal conjugate will be presented. A primary immune response was assessed in participants who had never received tetanus or pneumococcal conjugate vaccines previously and secondary/booster responses were assessed if the participants had previously received the vaccines. For pneumococcal conjugate vaccine, number of participants with \>= 2-fold increase in \>=6 pneumococcal serotypes from pre-vaccination timepoint to specified post-vaccination timepoints through the end of the study will be presented. For tetanus vaccine, number of participants with \>= 2-fold increase in participants with baseline titer \>=0.1 IU/mL from pre-vaccination timepoint to specified post-vaccination timepoints through the end of the study will be presented.
Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) - Pediatric Depression for Participants 5 to <18 Years at Study Entry	Baseline, Week 16	PROMIS is a set of person-centered measures that evaluates and monitors physical, mental and social health in adults and children. The PROMIS Depression item bank assesses self-reported negative mood (sadness, guilt), views on self (self-criticism, worthlessness), social cognition (loneliness, interpersonal alienation), decreased positive affect and engagement (loss of interest, meaning, and purpose). The PROMIS Depression Short Form (8a v2.0 and 6a v2.0) is available in pediatric self-report (ages 8 to \<18 years) and for parents/caregivers serving as proxy reporters for children (ages 5 to \<8 years). Children aged \<5 years will not complete assessment. Both pediatric self-report and proxy-report versions assess depression "in past seven days." Response options range from 1 = Never;2 = Rarely;3 = Sometimes;4 = Often; to 5 = Almost always. Total raw scores were converted to T-Scores (mean= 50 and a standard deviation = 10) with higher scores representing greater depression.
Change From Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16 for Participants 2 to <4 Years at Study Entry	Week 16	Infants' Dermatitis Quality of Life Index (IDQOL) is used to evaluate quality of life for subjects of age less than 4 years. IDQOL questionnaires were designed for infants (below the age of 4 years) with atopic dermatitis. The IDQOL was calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score in each questionnaire, the more quality of life is impaired. A negative change from baseline indicated improvement. LS Means were calculated using mixed model repeated measures (MMRM) model includes treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline on the European Quality of Life-5 Dimensions-Youth (EQ-5D-Y) for Participants 4 to <18 Years at Study Entry	Baseline, Week 16	The EQ-5D-Y questionnaire is health status related and self-completed for pediatric participants ≥8 years old and completed by parents/caregivers for children 4 to \<8 years old. Health state profile assessed health in 5 dimensions (Mobility,selfcare,usual activities,pain/discomfort, anxiety/depression) to obtain index score, each with three levels of response (no problems,some problems,a lot of problems). Participants indicated their health state by choosing appropriate level from each dimension. Visual analog scale on which participant rates their perceived health state from 0 ("worst health you can imagine") to 100 ("best health you can imagine") is presented.Higher the score the better the health status. LS Means uses MMRM model which includes treatment,age cohort,region,baseline disease severity(IGA),visit,treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in Skin Pain NRS for Participants 10 to <18 Years at Study Entry	Baseline, Week 16	Skin Pain NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LS Means were calculated using a MMRM model with treatment, age cohort, region, baseline disease severity (IGA), visit, treatment-by-age cohort interaction and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Number of Participant Responses With Tablet Acceptability and Palatability Assessment (PK Lead-In) for Participants >=10 Years Old at Study Entry	Week 2	The questionnaire for tablet acceptability and palatability assessed the participants ability to swallow the tablet. The questionnaire contained the question 1) How easy was it for you (your child) to swallow the medicine today? Responses: Very Easy, Easy, Neither Easy nor Hard, Difficult (or Hard) and Very Difficult (or Hard). The number of participants with these responses are presented. Data is presented as "Question Number-Response-Time point".
Pop PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY3009104	Predose; 0.25 hours (h); 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose	Pop PK: Cmax,ss was derived by a population pharmacokinetics approach.
Change From Baseline on the Work Productivity and Activity Impairment: Atopic Dermatitis - Caregiver (WPAI-AD-CG) Score	Baseline, Week 16	The Atopic Dermatitis Caregiver (WPAI-AD-CG) assesses the effect of a child's atopic dermatitis on the parent/caregiver's work productivity during the past 7 days. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, Scores are calculated as impairment percentages with higher scores indicating greater impairment and less productivity. LS Mean were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) for Participants 10 to <18 Years at Study Entry	Baseline, Week 16	Atopic Dermatitis Sleep Scale (ADSS) is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep, frequency of waking, and difficulty getting back to sleep last night. Item 2, frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep "last night." Each item is scored individually. LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by- visit-interaction as fixed continuous effects.
Number of Participant Responses With Suspension Acceptability and Palatability Assessment (PK Lead-In) for Participants <10 Years Old at Study Entry	Week 2	The questionnaire for Suspension acceptability and palatability assessed the participants ability to swallow the oral suspension product, experience relating to the taste, smell and ease of administering and taking the suspension. The questionnaire contained following Questions: Question 1) How did you (your child) like the taste of the medicine? Question 2) How did you (your child) like the smell of the medicine? Question 3) How easy was it for you (your child) to take the medicine today? Question 4) How easy was it for you to use the oral syringe to give your child the dose today? Responses: Liked Very Much, Liked, Neither Liked nor Disliked, Disliked, Disliked Very Much, Very Easy, Easy, Neither Easy nor Hard, Difficult (or Hard) and Very Difficult (or Hard). The number of participants with these responses are presented. Data is presented as "Question Number-Response-Time point".
Height, Weight and Body Mass Index (BMI) Growth Rate	124 Weeks	Height, Weight and BMI Growth Rate will be reported.

Trial Locations

Locations (78): Veracity Clinical Research
🇦🇺
Woolloongabba, Queensland, Australia
Faculdade de Medicina do ABC
🇧🇷
Santo André, Sao Paulo, Brazil
Fakultni Nemocnice v Motol
🇨🇿
Praha, Praha 5, Czechia
Instituto de Neumonología Y Dermatología
🇦🇷
Capital Federal, Buenos Aires, Argentina
Centro de Investigaciones Metabólicas (CINME)
🇦🇷
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Fundacion CIDEA
🇦🇷
Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina
Fundación Respirar
🇦🇷
Buenos Aires, Argentina
The Children's Hospital at Westmead
🇦🇺
Westmead, New South Wales, Australia
Royal Children's Hospital
🇦🇺
Melbourne, Victoria, Australia
Medizinische Universität Graz
🇦🇹
Graz, Steiermark, Austria
Medizinische Universität Wien
🇦🇹
Vienna, Wien, Austria
Sozialmedizinisches Zentrum Ost/Donauspital
🇦🇹
Vienna, Wien, Austria
Hospital de Clinicas de Porto Alegre
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
IBPClin - Instituto Brasil de Pesquisa Clínica
🇧🇷
Rio de Janeiro, Brazil
IDERJ - Instituto de Dermatologia e Estética do Brasil
🇧🇷
Rio de Janeiro, Brazil
Hospital do Servidor Público Estadual - IAMSPE - centro de estudos urológicos
🇧🇷
São Paulo, Brazil
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Hradec Králové, Czechia
Nemocnice AGEL Novy Jicin a.s.
🇨🇿
Novy Jicin, Nový Jičín, Czechia
Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan
🇫🇷
Brest, Finistère, France
Fakultni nemocnice Bulovka
🇨🇿
Prague, Praha 8, Czechia
Sanatorium profesora Arenbergera
🇨🇿
Praha 2, Czechia
Centre Hospitalier Universitaire de Nice - Hôpital l'Archet
🇫🇷
Nice, Alpes-Maritimes, France
Hôpitaux Drôme Nord - Romans
🇫🇷
Romans-sur-Isere, Drôme, France
Chu Saint Eloi
🇫🇷
Montpellier, Languedoc-Roussillon, France
Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
🇫🇷
Nantes, Loire-Atlantique, France
Universitaetsklinikum Carl Gustav Carus Dresden
🇩🇪
Dresden, Sachsen, Germany
Katholisches Kinderkrankenhaus Wilhelmstift
🇩🇪
Hamburg, Germany
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
🇭🇺
Szeged, Csongrad, Hungary
CHU de Toulouse - Hopital Larrey
🇫🇷
Toulouse, Midi-Pyrénées, France
Hôpital Saint Vincent de Paul
🇫🇷
Lille, Nord-Pas-de-Calais, France
Universitätsklinikum Frankfurt
🇩🇪
Frankfurt, Hessen, Germany
Universitätsklinikum Münster
🇩🇪
Münster, Nordrhein-Westfalen, Germany
Allergo-Derm Bakos Kft
🇭🇺
Szolnok, Jasz-Nagykun-Szolnok, Hungary
Aakash Healthcare: Super Speciality Hospital -Dwarka
🇮🇳
Dwarka, Delhi, India
Sheba Medical Center
🇮🇱
Ramat Gan, HaMerkaz, Israel
Emek Medical Center
🇮🇱
Afula, HaTsafon, Israel
Sourasky Medical Center
🇮🇱
Tel Aviv, Tell Abīb, Israel
Sir Ganga Ram Hospital
🇮🇳
New Delhi, Delhi, India
B. J. Medical College & Civil Hospital
🇮🇳
Ahmedabad, Gujarat, India
Soroka Medical Center
🇮🇱
Be'er Sheva, HaDarom, Israel
Nagoya Medical Center
🇯🇵
Nagoya, Aichi, Japan
Fukuyama City Hospital
🇯🇵
Fukuyama, Hiroshima, Japan
Takeda Dermatology Skincare Clinic
🇯🇵
Sapporo, Hokkaido, Japan
National Hospital Organization Sagamihara National Hospital
🇯🇵
Sagamihara, Kanagawa, Japan
National Mie Hospital
🇯🇵
Tsu, Mie, Japan
Kume Clinic
🇯🇵
Sakai City, Osaka, Japan
Senri-Chuo Hanafusa Dermatology Clinic
🇯🇵
Toyonaka, Osaka, Japan
Dokkyo Medical University Hospital
🇯🇵
Shimotsuga, Tochigi, Japan
Matsuda Tomoko Dermatological Clinic
🇯🇵
Fukuoka, Japan
Shinjuku Minamiguchi Hifuka
🇯🇵
Tokyo, Japan
Centro de Atención en Enfermedades Inflamatorias CATEI
🇲🇽
Guadalajara, Jalisco, Mexico
Centro Regiomontano de Investigación
🇲🇽
Monterrey, Nuevo León, Mexico
Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽
Monterrey, Nuevo León, Mexico
Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
🇲🇽
Durango, Mexico
Centrum Badan Klinicznych PI-House sp. z o.o.
🇵🇱
Gdansk, Pomorskie, Poland
Krasnodar Clinical Skin and Venereal Diseases Dispensary
🇷🇺
Krasnodar, Krasnodarskiy Kray, Russian Federation
Children's Health Research Center of RAMS
🇷🇺
Moscow, Moskva, Russian Federation
Arké SMO S.A de C.V
🇲🇽
Veracruz, Mexico
Specjalistyczne Gabinety Lekarskie "DERMED" Anna Kaszuba
🇵🇱
Lodz, Lodzkie, Poland
Diamond Clinic
🇵🇱
Krakow, Małopolskie, Poland
Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology - Central branch
🇷🇺
Moscow, Moskva, Russian Federation
Tula Regional Clinical Dermatovenerological Dispensary
🇷🇺
Tula, Tul'skaya Oblast', Russian Federation
Hospital Sant Joan de Déu
🇪🇸
Esplugues de Llobregat, Barcelona [Barcelona], Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸
Majadahonda, Madrid, Comunidad De, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸
Pozuelo de Alarcon, Madrid, Spain
Clinica Universidad de Navarra
🇪🇸
Pamplona, Navarra, Spain
CHOP-Centro De Especialidades De Mollabao
🇪🇸
Pontevedra, Pontevedra [Pontevedra], Spain
Hospital Infantil Universitario Niño Jesús
🇪🇸
Madrid, Spain
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Chang Gung Memorial Hospital at Kaohsiung
🇨🇳
Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan
Chung Shan Medical University Hospital
🇨🇳
Taichung City, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳
Taipei, Taiwan
Chang Gung Medical Foundation-Linkou Branch
🇨🇳
Taoyuan, Taiwan
Chang Gung Memorial Hospital - Linkou Branch
🇨🇳
Taoyuan, Taiwan
Royal Hospital for Sick Children
🇬🇧
Glasgow, Glasgow City, United Kingdom
St Thomas's Hospital
🇬🇧
London, London, City Of, United Kingdom
Queen's Medical Centre, Nottingham University Hospitals
🇬🇧
Nottingham, Nottinghamshire, United Kingdom