A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis That Are Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Advisable (BREEZE-AD4)

A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety and Efficacy of Baricitinib in Combination With Topical Corticosteroids in Adult Patients With Moderate-to-Severe Atopic Dermatitis Who Have Experienced Failure to Cyclosporine or Are Intolerant to, or Have Contraindication to, Cyclosporine

The purpose of this study is to determine the efficacy and safety of baricitinib in combination with topical corticosteroids in participants with moderate to severe atopic dermatitis who have experienced failure to cyclosporine or are intolerant to, or have contraindication to cyclosporine.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo; Drug: Baricitinib; Drug: Topical corticosteroid

• Study Type: Interventional
• Enrollment (Actual): 463
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1220
    • Sozialmed. Zentrum Ost - Donauspital
  • Wien, Austria, 1090
    • AKH
  • Wien, Austria, 1030
    • KA Rudolfstiftung
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Universitätsklinikum Graz
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Universitätsklinik Innsbruck
• Belgium
  • Brussel, Belgium, 1090
    • Universitair Ziekenhuis Brussel
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • UZ Leuven - Campus Sint-Rafaël
• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Hospital da Clinicas da Faculdade de Medicina da USP
  • ES
    • Vitoria, ES, Brazil, 29055 450
      • Cedoes Centro Diagnostico Pequisa Osteoporose E Santo Ltd
  • RJ
    • Rio de Janeiro, RJ, Brazil, 22470-220
      • IDERJ - Instituto de Dermatologia e Estética do Brasil
    • Rio de Janeiro, RJ, Brazil, 22271-100
      • CCBR Brasil Centro de Analises e Pesquisas Clínicas LTDA
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90560-030
      • Hospital Moinhos de Vento - Instituto de Educação e Pesquisa
  • SP
    • Ribeirao Preto, SP, Brazil, 14048-900
      • Hospital das Clinicas da FMRP
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083-887
      • Faculdade de Ciências Médicas - UNICAMP
    • Santo André, Sao Paulo, Brazil, 09060-650
      • Fundação Faculdade de Medicina do ABC
• Finland
  • Helsinki, Finland, 00250
    • Helsinki University Central Hospital
  • Turku, Finland, 20520
    • Hospital Mehiläinen Neo
  • Irkanmaa
    • Tampere, Irkanmaa, Finland, 33100
      • Terveystalo Tampere
• France
  • Besancon Cedex, France, 25030
    • CHU de Besancon Hopital Jean Minjoz
  • Bordeaux Cedex, France, 33075
    • CHU de Bordeaux Hôpital Saint André
  • Lille, France, 59037
    • Hôpital C. HURIEZ
  • Mulhouse, France, 68100
    • Hôpital Emile Muller
  • Nantes Cedex 1, France, 44093
    • Chru De Nantes Hotel-Dieu
  • Nice cedex 3, France, 06202
    • Chu de Nice Hopital de L'Archet
  • Toulon Cedex 9, France, 83800
    • Hopital Sainte Anne (H.I.A)
  • Toulouse cedex 9, France, 31059
    • Hopital Larrey
  • Valence, France, 26953
    • Centre Hospitalier de Valence
  • Cedex 9
    • Rennes, Cedex 9, France, 35033
      • Hôpital de Pontchaillou
• Germany
  • Berlin, Germany, 10117
    • Charite Universitatsmedizin Berlin
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg - Eppendorf
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • UniversitatsKlinikum Heidelberg
    • Stuttgart, Baden-Württemberg, Germany, 70178
      • Hautarztpraxis Dr. Leitz und Kollegen
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Universitatsklinikum Erlangen
    • München, Bayern, Germany, 80802
      • Klinikum rechts der Isar der TU Munchen
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
  • Niedersachsen
    • Buxtehude, Niedersachsen, Germany, 21614
      • Elbe Kliniken Stade Buxtehude GmbH Klinikum Buxtehude
    • Hannover, Niedersachsen, Germany, 30449
      • Medizinische Hochschule Hannover
    • Osnabrück, Niedersachsen, Germany, 49074
      • Klinische Forschung Osnabrück
  • Nordrhein-Westfalen
    • Bad Bentheim, Nordrhein-Westfalen, Germany, 48455
      • Fachklinik Bad Bentheim
    • Bochum, Nordrhein-Westfalen, Germany, 44791
      • St Josef-Hospital Bochum
    • Bonn, Nordrhein-Westfalen, Germany, 53127
      • Universitatsklinikum Bonn
    • Essen, Nordrhein-Westfalen, Germany, 45147
      • Universitaetsklinikum Essen
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitatsklinikum Munster
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Thüringen
    • Jena, Thüringen, Germany, 07743
      • Universitätsklinikum Jena
• Italy
  • Ancona, Italy, 60020
    • Azienda Ospedaliera Umberto I
  • Brescia, Italy, 25123
    • Spedali Civili - Universita degli Studi
  • Chieti, Italy, 66100
    • Fondazione Universitaria degli Studi G D'Annunzio
  • Perugia, Italy, 06129
    • Azienda Ospedaliera di Perugia
  • Reggio Emilia, Italy, 42123
    • Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia
  • Roma, Italy, 00133
    • Policlinico di Tor Vergata
  • Verona, Italy, 37134
    • Ospedale Policlinico Giambattista Rossi, Borgo Roma
  • Milan
    • Milano, Milan, Italy, 20122
      • Fondazione IRCCS Osp.Maggiore Policlinico - Dermatologia
    • San Donato Milanese, Milan, Italy, 20097
      • Ospedale Clinicizzato San Donato
  • Rome
    • Roma, Rome, Italy, 00161
      • Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
• Japan
  • Chiba
    • Ainokawa, Ichikawa-shi, Chiba, Japan, 272-0143
      • Yanagihara dermatology clinic
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 815-0082
      • Fumimori Clinic
  • Kanagawa
    • Nishi-ku, Yokohama-city, Kanagawa, Japan, 220-6208
      • Queen's Square Dermatology and Allergology
  • Kumamoto
    • Kashima-machi, Kamimashiki-gun, Kumamoto, Japan, 861-3101
      • Noguchi Dermatology
  • Osaka
    • Neyagawa-shi, Osaka, Japan, 572-0838
      • Yoshioka Dermatology Clinic
    • Nishi-ku Sakai-shi, Osaka, Japan, 593-8324
      • Kume Clinic
  • Saitama
    • Ohmiya-ku,Saitama-shi, Saitama, Japan, 330-0854
      • Sanrui Dermatology Clinic
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 102-0072
      • Iidabashi Clinic
    • Chuo-ku, Tokyo, Japan, 103-0025
      • Nihonbashi Sakura Clinic
    • Edogawa-ku, Tokyo, Japan, 133-0057
      • Sumire Dermatology Clinic
    • Tachikawa-shi, Tokyo, Japan, 190-0023
      • Tachikawa Dermatology Clinic
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Bergen op Zoom, Netherlands, 4624 VT
    • Bravis Ziekenhuis
  • Breda, Netherlands, 4818 CK
    • Amphia Ziekenhuis
• Poland
  • Bialystok, Poland, 15-375
    • NZOZ Specjalistyczna Przychodnia Dermatologiczna Specderm
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych, PI House
  • Katowice, Poland, 40-611
    • Centrum Medyczne Angelius Provita
  • Krakow, Poland, 31-559
    • Barbara Rewerska Diamond Clinic
  • Lodz, Poland, 90-265
    • Dermed Centrum Medyczne Sp. z o.o.
  • Olsztyn, Poland, 10-229
    • Miejski Szpital Zespolony w Olsztynie Klinika Dermatologii
  • Osielsko, Poland, 86-031
    • DermoDent, Centrum Medyczne Czajkowscy
  • Szczecin, Poland, 70-332
    • LASER CLINIC Specjalistyczne Gabinety Lekarskie
  • Warsaw, Poland, 04-141
    • Wojskowy Instytut Medyczny CSK MON
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny MSW Klinika Dermatologii
• Russian Federation
  • Moscow, Russian Federation, 119991
    • First Moscow State Medical University n.a. Sechenov
  • Moscow, Russian Federation, 107076
    • State scientific centre for dermatovenerology and cosmetolog
  • Saint-Petersburg, Russian Federation, 194223
    • LLC ArsVitae NorthWest
  • Saint-Petersburg, Russian Federation, 196240
    • LLC Medical Center "Kurator"
  • St. Petersburg, Russian Federation, 194021
    • SPb SBHI Skin-venerologic dispensary #10
• Spain
  • Valencia, Spain, 46017
    • Hospital Universitario Dr Pesset
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
  • Madrid
    • Majadahonda, Madrid, Spain, 28220
      • Hospital Univ. Puerta de Hierro
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Universitario Quiron Madrid
    • Torrejón de Ardoz, Madrid, Spain, 28850
      • Hospital Universitario de Torrejon
  • Valencia
    • Manises, Valencia, Spain, 46940
      • Hospital de Manises
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Zürich, Switzerland, 8091
    • Universitätsspital Zürich
  • Sankt Gallen
    • St. Gallen, Sankt Gallen, Switzerland, 9007
      • Kantonsspital St. Gallen
• United Kingdom
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Salford Royal NHS Foundation Trust
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G3 8SJ
      • West Glasgow Ambulatory Care Hospital
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Whipps Cross University Hospital
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L14 3LB
      • Broadgreen Hospital
  • Surrey
    • London, Surrey, United Kingdom, SE1 9RT
      • Guys/St. Thomas Hospital
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • The Dudley Group NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have been diagnosed with moderate to severe Atopic Eczema (Atopic Dermatitis) for at least 12 months.
• Have had inadequate response 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.
• Have a medical contraindication to cyclosporine, or had intolerance and/or unacceptable toxicity or inadequate response to cyclosporine in the past.

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 episodes of eczema herpeticum in the past.
• Participants who are currently experiencing a skin infection that requires treatment, or are 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 randomization.
  • Received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks prior to randomization.
  • Received oral corticosteroids within 4 weeks prior to randomization or parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization 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 randomization.
• Have high blood pressure characterized by a repeated systolic blood pressure >160 millimeters of mercury (mm Hg) or diastolic blood pressure >100 mm Hg.
• 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 recurrent (≥ 2) 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 and/or clinically serious viral, bacterial, fungal, or parasitic infection including herpes zoster, 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4 mg Baricitinib; 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.	Drug: Placebo; Administered orally.; Drug: Baricitinib; Administered orally.; Other Names: LY3009104; Drug: Topical corticosteroid; Administered as standard-of-care.
Experimental: 2 mg Baricitinib; 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.	Drug: Placebo; Administered orally.; Drug: Baricitinib; Administered orally.; Other Names: LY3009104; Drug: Topical corticosteroid; Administered as standard-of-care.
Experimental: 1 mg Baricitinib; 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.	Drug: Placebo; Administered orally.; Drug: Baricitinib; Administered orally.; Other Names: LY3009104; Drug: Topical corticosteroid; Administered as standard-of-care.
Placebo Comparator: Placebo; Placebo administered orally once daily in combination with topical corticosteroids.	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 Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)	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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving IGA of 0	The IGA measures the investigator's global assessment of the participant's overall severity of their AD, 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
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	Percentage of participants developing skin infections requiring antibiotic treatment.	Week 16
Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)	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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who permanently discontinue, are rescued, or are without at least 1 post-baseline observation.	Week 16
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement	The IGA measures the investigator's global assessment of the participant's overall severity of their AD, 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
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 (no disease) to 72 (severe disease). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.	Week 16
Percent 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 was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). Least Squares Mean (LSM) were calculated using mixed model repeated measures (MMRM) model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline score and baseline score-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 a visual analogue scales (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)	The Itch 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 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.	Week 16
Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)	The ADSS is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep due to itch, frequency of waking due to itch, and difficulty getting back to sleep last night due to itch. 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 Mean were calculated using an MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Change From Baseline in Skin Pain NRS	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 Mean were calculated using MMRM model includes 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
Percentage of Participants Achieving IGA of 0 or 1 With a >=2-point Improvement	The IGA measures the investigator's global assessment of the participant's overall severity of their AD, 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 24
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: (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 (no disease) to 72 (severe disease). The EASI50 is defined as a ≥ 50% improvement from baseline in the EASI score.	Week 16
Percentage of Participants Achieving 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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.	Week 24
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 Mean were calculated using 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
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 a visual analogue scales (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 SCORAD90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the SCORAD score.	Week 16
Change From Baseline in Body Surface Area (BSA) Affected	The BSA affected by AD 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. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1*BSAhead and neck + 0.3*BSAtrunk + 0.2* BSAupper limbs + 0.4*BSAlower limbs. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Mean Number of Days Without Topical Corticosteroids (TCS) Use	The ANCOVA model includes treatment, region, and baseline disease severity (IGA) as factors.	Week 16
Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)	Average weights of full tubes were used to determine the dispensed weights for each region. Returned tubes were weighed with cap without carton to determine the amount of TCS in grams (g) 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.	Week 16
Percent Change From Baseline in Itch NRS	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 MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.	Baseline, Week 16
Percent Change From Baseline in Itch NRS at Week 24	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 MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.	Baseline, Week 24
Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)	The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. LS Mean were calculated using 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-interactions as fixed continuous effects.	Baseline, Week 16
Change From Baseline in the Patient Global Impression of Severity - Atopic Dermatitis (PGI-S-AD) Score	The PGI-S-AD is a single-item question asking the participant how they would rate their overall AD symptoms over the past 24 hours, using a daily diary. The 5 categories of responses are "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe." LS Means were calculated using 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 on the Hospital Anxiety Depression Scale (HADS)	The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' LS Mean were calculated using 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 the Dermatology Life Quality Index (DLQI)	The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a little," "a lot," and "very much," with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or "not relevant" responses scored as "0." Scores range from 0 to 30 ("no impact on participant's life" to "extremely large effect on participant's life"), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LS Means were calculated using 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 on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire	The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. 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%, with higher values indicating greater impairment. LS Means were calculated using 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 the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm	The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using 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 on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)	EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16

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

General Publications

• King B, Maari C, Lain E, Silverberg JI, Issa M, Holzwarth K, Brinker D, Cardillo T, Nunes FP, Simpson EL. Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials. Am J Clin Dermatol. 2021 May;22(3):395-405. doi: 10.1007/s40257-021-00602-x. Epub 2021 Apr 7.
• Katoh N, Takita Y, Isaka Y, Nishikawa A, Torisu-Itakura H, Saeki H. Pooled Safety Analysis of Baricitinib in Adult Participants with Atopic Dermatitis in the Japanese Subpopulation from Six Randomized Clinical Trials. Dermatol Ther (Heidelb). 2022 Dec;12(12):2765-2779. doi: 10.1007/s13555-022-00828-5. Epub 2022 Oct 18.

Helpful Links

• A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis (Eczema) Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Adv

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2018
• Primary Completion (Actual): November 25, 2019
• Study Completion (Actual): April 20, 2023

Study Registration Dates

• First Submitted: February 5, 2018
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 20, 2023
• Last Verified: May 15, 2023

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: 16841; I4V-MC-JAIN (Other Identifier: Eli Lilly and Company); 2017-004574-34 (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 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