A Study of Baricitinib (LY3009104) in Children and Adolescents With Atopic Dermatitis (BREEZE-AD-PEDS)

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Outpatient Study Evaluating the Pharmacokinetics, Efficacy, and Safety of Baricitinib in Pediatric Patients With Moderate to Severe Atopic Dermatitis

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo; Drug: Baricitinib; Drug: Topical corticosteroid

• Study Type: Interventional
• Enrollment (Actual): 516
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ABP
    • Fundación Respirar
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1425
      • Instituto de Neumonologia y Dermatologia
  • Ciudad Autonoma Buenos Aires
    • Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina, C1121ABE
      • Fundacion Cidea
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Veracity Clinical Research Pty Ltd
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Royal Children's Hospital
• Austria
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medizinische Universität Graz
  • Vienna
    • Wien, Vienna, Austria, 1090
      • Medizinische Universitat Wien
  • Wien
    • Vienna, Wien, Austria, 1220
      • Sozialmedizinisches Zentrum Ost/Donauspital
• Brazil
  • Rio de Janeiro, Brazil, 22470-220
    • IDERJ - Instituto de Dermatologia e Estética do Brasil
  • Rio de Janeiro, Brazil, 20241180
    • IBPClin - Instituto Brasil de Pesquisa Clínica
  • São Paulo, Brazil, 04039-901
    • Hospital do Servidor Público Estadual - IAMSPE - centro de estudos urológicos
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
  • Sao Paulo
    • Santo André, Sao Paulo, Brazil, 09060-650
      • Fundação Faculdade de Medicina do ABC
• Czechia
  • Praha 2, Czechia, 128 00
    • Sanatorium Profesora Arenbergera
  • Hradec Králové
    • Hradec Kralove, Hradec Králové, Czechia, 500 05
      • Fakultni nemocnice Hradec Kralove
  • Nový Jičín
    • Novy Jicin, Nový Jičín, Czechia, 741 01
      • Nemocnice AGEL Novy Jicin a.s.
  • Praha 5
    • Praha, Praha 5, Czechia, 150 06
      • Fakultni nemocnice v Motole
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 6200
      • Centre Hospitalier Universitaire de Nice - Hôpital l'Archet
  • Drôme
    • Romans-sur-Isere, Drôme, France, 26102
      • Hôpitaux Drôme Nord - Romans
  • Finistère
    • Brest, Finistère, France, 29200
      • Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan
  • Languedoc-Roussillon
    • Montpellier, Languedoc-Roussillon, France, 34295
      • CHU Saint Eloi
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
  • Midi-Pyrénées
    • Toulouse, Midi-Pyrénées, France, 31400
      • CHU de Toulouse - Hopital Larrey
  • Nord-Pas-de-Calais
    • Lille, Nord-Pas-de-Calais, France, 59020
      • Hôpital Saint Vincent de Paul
• Germany
  • Hamburg, Germany, 22149
    • Katholisches Kinderkrankenhaus Wilhelmstift
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • Universitatsklinikum Frankfurt
  • Nordrhein-Westfalen
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitätsklinikum Münster
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden
• Hungary
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
  • Jasz-Nagykun-Szolnok
    • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000
      • Allergo-Derm Bakos Kft
• India
  • Delhi
    • Dwarka, Delhi, India, 110075
      • Aakash Healthcare: Super Speciality Hospital -Dwarka
  • Gujarat
    • Ahmedabad, Gujarat, India, 380016
      • B. J. Medical College & Civil Hospital
• Israel
  • HaDarom
    • Be'er Sheva, HaDarom, Israel, 8410101
      • Soroka Medical Center
  • HaMerkaz
    • Ramat Gan, HaMerkaz, Israel, 5262100
      • Sheba Medical Center
  • HaTsafon
    • Afula, HaTsafon, Israel, 1834111
      • Emek Medical Center
  • Tell Abīb
    • Tel Aviv, Tell Abīb, Israel, 6423906
      • Sourasky Medical Center
• Japan
  • Fukuoka, Japan, 819-0167
    • Matsuda Tomoko Dermatological Clinic
  • Tokyo, Japan, 160-0023
    • Shinjuku Minamiguchi Hifuka
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
      • Nagoya Medical Center
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 721-8511
      • Fukuyama City Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 004-0063
      • Takeda Dermatology Skincare Clinic
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 252-0392
      • National Hospital Organization Sagamihara National Hospital
  • Mie
    • Tsu, Mie, Japan, 514-0125
      • National Mie Hospital
  • Osaka
    • Sakai City, Osaka, Japan, 593-8324
      • Kume Clinic
    • Toyonaka, Osaka, Japan, 560-0085
      • Senri-Chuo Hanafusa Dermatology Clinic
  • Tochigi
    • Shimotsuga, Tochigi, Japan, 321-0293
      • Dokkyo Medical University Hospital
• Mexico
  • Durango, Mexico, 34000
    • Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
  • Veracruz, Mexico, 91910
    • Arké SMO S.A de C.V
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44638
      • Centro de Atención en Enfermedades Inflamatorias CATEI
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio González
    • Monterrey, Nuevo León, Mexico, 64060
      • Centro Regiomontano de Investigacion
• Poland
  • Lodzkie
    • Lodz, Lodzkie, Poland, 90-265
      • Dermed Centrum Medyczne Sp. z o.o.
  • Małopolskie
    • Krakow, Małopolskie, Poland, 31-559
      • Diamond Clinic
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-546
      • Centrum Badań Klinicznych PI-House sp. z o.o.
• Russian Federation
  • Krasnodarskiy Kray
    • Krasnodar, Krasnodarskiy Kray, Russian Federation, 354057
      • Krasnodar Clinical Skin and Venereal Diseases Dispensary
  • Moskva
    • Moscow, Moskva, Russian Federation, 115478
      • Children's Health Research Center of RAMS
    • Moscow, Moskva, Russian Federation, 127473
      • Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology - Central branch
  • Tul'skaya Oblast'
    • Tula, Tul'skaya Oblast', Russian Federation, 300053
      • Tula Regional Clinical Dermatovenerological Dispensary
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus
  • Barcelona [Barcelona]
    • Esplugues de Llobregat, Barcelona [Barcelona], Spain, 8950
      • Hospital Sant Joan de Deu
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Universitario Quirónsalud Madrid
  • Madrid, Comunidad De
    • Majadahonda, Madrid, Comunidad De, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra
  • Pontevedra [Pontevedra]
    • Pontevedra, Pontevedra [Pontevedra], Spain, 36001
      • CHOP-Centro De Especialidades De Mollabao
• Taiwan
  • Taichung City, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou Branch
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou Branch
  • Kaohsiung
    • Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan, 83301
      • Chang Gung Memorial Hospital at Kaohsiung
• United Kingdom
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G514TF
      • Royal Hospital for Sick Children
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 7EH
      • St Thomas's Hospital
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Queen's Medical Centre, Nottingham University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Baricitinib Open Label High Dose (PK Lead-in); 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.	Drug: Baricitinib; Administered orally; Other Names: LY3009104; Drug: Topical corticosteroid; Administered as standard-of-care
Experimental: Baricitinib High Dose; 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.	Drug: Baricitinib; Administered orally; Other Names: LY3009104; Drug: Topical corticosteroid; Administered as standard-of-care
Experimental: Baricitinib Medium Dose; 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.	Drug: Baricitinib; Administered orally; Other Names: LY3009104; Drug: Topical corticosteroid; Administered as standard-of-care
Experimental: Baricitinib Low Dose; 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.	Drug: Baricitinib; Administered orally; Other Names: LY3009104; Drug: Topical corticosteroid; Administered as standard-of-care
Placebo Comparator: Placebo; Participants 10 to < 18 years received placebo tablets. Participants 2 to < 10 years received placebo as oral suspension.	Drug: Placebo; Administered orally; Drug: Topical corticosteroid; Administered as standard-of-care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥2 Point Improvement	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.	Week 16
Open Label Population Pharmacokinetics (Pop PK): Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY3009104	Open label Pop PK: Cmax,ss was derived by a population pharmacokinetics approach.	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: Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of LY3009104	Open label Pop PK: AUCtau,ss was derived by a population pharmacokinetics approach.	Predose; 0.25 h; 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)	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.	Week 16
Percentage of Participants Achieving SCORAD90	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.	Week 16
Percentage of Participants Achieving EASI90	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.	Week 16
Change From Baseline in EASI Score	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.	Baseline, Week 16
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)	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.	Week 16
Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) for Participants 10 to <18 Years Old at Study Entry	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.	Week 16
Percentage of Participants Achieving EASI50	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.	Week 16
Percentage of Participants Achieving IGA of 0	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.	Week 16
Change From Baseline in SCORAD	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.	Baseline, Week 16
Change From Baseline in Body Surface Area (BSA) Affected	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.	Baseline, Week 16
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	Percentage of participants developing skin infections requiring antibiotic treatment	Week 16
Mean Number of Days Without Use of Background Topical Corticosteroid (TCS)	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.	Baseline Through 16 Weeks
Mean Gram Quantity of TCS Use (Tube Weights)	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.	Baseline through 16 Weeks
Change From Baseline in Itch NRS for Participants 10 to <18 Years at Study Entry	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.	Baseline, Week 16
Change From Baseline in the Parent-Reported Itch Severity Measure (PRISM) for Participants 2 to <10 Years at Study Entry	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.	Baseline, Week 16
Change From Baseline on the Patient-Oriented Eczema Measure (POEM) Total Score	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.	Baseline, Week 16
Change From Baseline in Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score for Participants 10 to <18 Years at Study Entry	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.	Baseline, Week 16
Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) - Pediatric Depression for Participants 5 to <18 Years at Study Entry	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.	Baseline, Week 16
Change From Baseline in the PROMIS-Pediatric Anxiety for Participants 5 to <18 Years at Study Entry	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.	Baseline, Week 16
Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) at Week 16 for Participants 4 to <18 Years at Study Entry	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.	Baseline, Week 16
Change From Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16 for Participants 2 to <4 Years at Study Entry	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.	Week 16
Change From Baseline on the Work Productivity and Activity Impairment: Atopic Dermatitis - Caregiver (WPAI-AD-CG) Score	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.	Baseline, Week 16
Change From Baseline on the European Quality of Life-5 Dimensions-Youth (EQ-5D-Y) for Participants 4 to <18 Years at Study Entry	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.	Baseline, Week 16
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	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.	Baseline, Week 16
Change From Baseline in Skin Pain NRS for Participants 10 to <18 Years at Study Entry	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.	Baseline, Week 16
Number of Participant Responses With Suspension Acceptability and Palatability Assessment (PK Lead-In) for Participants <10 Years Old at Study Entry	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".	Week 2
Number of Participant Responses With Tablet Acceptability and Palatability Assessment (PK Lead-In) for Participants >=10 Years Old at Study Entry	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".	Week 2
Height, Weight and Body Mass Index (BMI) Growth Rate	Height, Weight and BMI Growth Rate will be reported.	124 Weeks
Change of Immunoglobulin G (IgG) Titers	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.	Baseline Through End of Study Completion
Pop PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY3009104	Pop PK: Cmax,ss was derived by a population pharmacokinetics approach.	Predose; 0.25 hours (h); 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose
Pop PK: Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of LY3009104	Pop PK: AUCtau,ss was derived by a population pharmacokinetics approach.	Predose; 0.25 hours (h); 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Incyte Corporation
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of Baricitinib (LY3009104) in Children and Adolescents With Atopic Dermatitis (BREEZE-AD-PEDS)

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2019
• Primary Completion (Actual): April 24, 2022
• Study Completion (Estimated): May 22, 2026

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: eczema; atopic eczema
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: 16966; I4V-MC-JAIP (Other Identifier: Eli Lilly and Company); 2018-000349-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes