A Study of Baricitinib (LY3009104) in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis (BREEZE-AD7)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Combination With Topical Corticosteroids in Adult Patients With Moderate to Severe Atopic Dermatitis BREEZE-AD7

The purpose of this study is to evaluate the efficacy and safety of baricitinib in combination with topical corticosteroids (TCS) in participants with moderate to severe atopic dermatitis.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 329
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1425BEA
    • Instituto de Neumonologia y Dermatologia
  • Ciudad Autonoma Buenos Aires, Argentina, C1425DKG
    • Psoriahue Medicina Interdisciplinaria
  • Ciudad Autonoma Buenos Aires, Argentina, C1121ABE
    • Fundacion Cidea
  • Ciudad Autonoma Buenos Aires, Argentina, C1056ABJ
    • Centro de Investigaciones Metabólicas (CINME) - Comite
  • Mendoza, Argentina, 5500
    • Parra Dermatología
• Australia
  • Australian Capital Territory
    • Phillip, Australian Capital Territory, Australia, 2606
      • Woden Dermatology
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Skin & Cancer Foundation Australia
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • The Skin Centre
    • Woolloongabba, Queensland, Australia, 4102
      • Veracity Clinical Research Pty Ltd
  • South Australia
    • Adelaide, South Australia, Australia, 5073
      • Clinical Trials SA Pty Ltd
  • Victoria
    • Melbourne, Victoria, Australia, 3053
      • Skin and Cancer Foundation Inc.
  • Western Australia
    • Perth, Western Australia, Australia, 6160
      • Fremantle Dermatology
• Austria
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Universitätsklinikum Graz
• Germany
  • Berlin, Germany, 10117
    • Charite Universitatsmedizin Berlin
  • Hamburg, Germany, 20537
    • TFS Trial Form Support GmbH
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Universitätsklinikum Heidelberg
  • Bayern
    • München, Bayern, Germany, 80337
      • Klinikum der Universität München
  • Hessen
    • Darmstadt, Hessen, Germany, 64283
      • Rosenpark Research Geschäftsbereich der Rosenparkklinik GmbH
  • Niedersachsen
    • Bramsche, Niedersachsen, Germany, 49565
      • Dermatologisches Zentrum Osnabrück Nord
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Universitätsklinikum Aachen - UKA
    • Essen, Nordrhein-Westfalen, Germany, 45147
      • Universitaetsklinikum Essen
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitatsklinikum Munster
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitatsklinikum Schleswig-Holstein
• Italy
  • Genova, Italy, 16132
    • Azienda Ospedaliera Universitaria Ospedale San Martino di Genova
  • Pisa, Italy, 56126
    • Azienda Ospedaliera - Universitaria Pisana
  • Vicenza, Italy, 36100
    • ULSS 8 UOC Dermatologia Viale Rodolfi, 37
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Policlinico Univ. Agostino Gemelli
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas
• Japan
  • Chiba
    • Ichikawa-shi, Chiba, Japan, 272-0033
      • Kawashima Dermatology Clinic
    • Matsudo-shi, Chiba, Japan, 271-0092
      • Medical Corporation Soleil Miyata Dermatology Clinic
  • Fukuoka
    • Dazaifu, Fukuoka, Japan, 818-0104
      • Yamano Dermatological Clinic
    • Iizuka-city, Fukuoka, Japan, 820-0040
      • TASHIRO Dermatological Clinic
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0063
      • Sapporo Skin Clinic
    • Sapporo, Hokkaido, Japan, 006 0022
      • Shibaki Dermatology Clinic
  • Kanagawa
    • Nishi-ku, Yokohama-city, Kanagawa, Japan, 220-6208
      • Queen's Square Dermatology and Allergology
  • Osaka
    • Neyagawa-shi, Osaka, Japan, 572-0838
      • Yoshioka Dermatology Clinic
    • Toyonaka-shi, Osaka, Japan, 560-0085
      • Senri-Chuo Hanafusa Dermatology Clinic
  • Shizuoka
    • Hamamatsu-shi, Shizuoka, Japan, 430-0929
      • JA Shizuoka Kohseiren Enshu Hospital
  • Tokyo
    • Chiyoda-Ku, Tokyo, Japan, 102-8798
      • Tokyo Teishin Hospital
    • Chiyoda-ku, Tokyo, Japan, 102-0072
      • Iidabashi Clinic
    • Chuo-ku, Tokyo, Japan, 104-0031
      • Hosono Clinic
    • Nerima-ku, Tokyo, Japan, 178-0063
      • Oizumi Hanawa Clinic
    • Shinjuku, Tokyo, Japan, 169-0075
      • Yamate Dermatological Clinic
    • Tachikawa-shi, Tokyo, Japan, 190-0023
      • Tachikawa Dermatology Clinic
  • Toyama
    • Takaoka-shi, Toyama, Japan, 9330871
      • Shirasaki Clinic
• Korea, Republic of
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacred Heart Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, Korea, Republic of, 06973
    • Chungang University Hospital
  • Seoul, Korea, Republic of, 06591
    • Seoul st. mary's hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Hospital
  • Gyeonggi-do
    • Ansan-si, Gyeonggi-do, Korea, Republic of, 15355
      • Korea University Ansan Hospital
    • Goyang, Gyeonggi-do, Korea, Republic of, 10326
      • Dongguk University Ilsan Hospital
  • Korea
    • Incheon, Korea, Korea, Republic of, 21565
      • Gachon University Gil Medical Center
• Poland
  • Lodz, Poland, 90-265
    • Dermed Centrum Medyczne Sp. z o.o.
  • Swidnik, Poland, 21-040
    • Lubelskie Centrum Diagnostyczne
  • Warszawa, Poland, 01-518
    • Centrum Medyczne AMED
  • Warszawa, Poland, 02-625
    • Centrum Medyczne Evimed
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Cordoba, Spain, 14004
    • Hospital Reina Sofia
  • Las Palmas de Gran Canaria, Spain, 35010
    • Hospital De Gran Canaria Dr. Negrin
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Chang Gung Memorial Hospital - Kaohsiung
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University- Shuang Ho Hospital
  • Taichung City, Taiwan, 40201
    • Chung Shan Medical University Hospital
  • Taipei, Taiwan, 10508
    • Chang Gung Memorial Hospital - Taipei
  • Taipei City, Taiwan, 10048
    • National Taiwan University Hospital
  • Taoyuan, (r.o.c.), Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have been diagnosed with moderate to severe 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.

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 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 randomization.
  • Received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks prior to randomization.
  • Received any parenteral corticosteroids administered by intramuscular or intravenous (IV) injection 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 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 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
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 4 Milligram (mg) Baricitinib; 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids (TCS). Placebo administered orally once daily to match 2 mg Baricitinib.	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 TCS. Placebo administered orally once daily to match 4 mg Baricitinib.	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 TCS.	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	The IGA measures investigators global assessment of the participant's overall severity of their atopic dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 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
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
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
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.	Week 16
Percent Change From Baseline on 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 to 72 (severe). Least Squares Mean (LSM) were calculated using mixed model repeated measures (MMRM) 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 a 4-Point Improvement in Itch Numeric Rating Scale (NRS)	The Itch NRS is a patient-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 a 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
Change From Baseline in Skin Pain NRS	Skin Pain NRS is a patient-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, 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 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 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in the EASI score.	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
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. The SCORAD90 is defined as 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 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
Mean Gram Quantity of 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 (IGA) and treatment as factors in the model.	Week 0 through Week 16
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 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 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 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 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 lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and at unanswered ("not relevant") responses scored as "0." Scores range from 0 to 30 (less to more impairment), 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 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 EQ-5D-5L Visual Analog Scale (VAS)	The EQ-5D-5L is a 2-part measurement. The second part is assessed using a 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-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Mean Number of Days Without Use of Background TCS	The ANCOVA model includes treatment, region, and baseline disease severity (IGA) as factors.	Week 0 through 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 4

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Incyte Corporation

Publications and helpful links

General Publications

• 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.
• Thyssen JP, Buhl T, Fernandez-Penas P, Kabashima K, Chen S, Lu N, DeLozier AM, Casillas M, Stander S. Baricitinib Rapidly Improves Skin Pain Resulting in Improved Quality of Life for Patients with Atopic Dermatitis: Analyses from BREEZE-AD1, 2, and 7. Dermatol Ther (Heidelb). 2021 Oct;11(5):1599-1611. doi: 10.1007/s13555-021-00577-x. Epub 2021 Jul 18.
• 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.
• Buhl T, Rosmarin D, Serra-Baldrich E, Fernandez-Penas P, Igarashi A, Konstantinou MP, Chen S, Lu N, Pierce E, Casillas M. Itch and Sleep Improvements with Baricitinib in Patients with Atopic Dermatitis: A Post Hoc Analysis of 3 Phase 3 Studies. Dermatol Ther (Heidelb). 2021 Jun;11(3):971-982. doi: 10.1007/s13555-021-00534-8. Epub 2021 Apr 25.
• Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, Kaszuba A, Kolodsick J, Yang FE, Gamalo M, Brinker DR, DeLozier AM, Janes JM, Nunes FP, Thyssen JP, Simpson EL. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Dec 1;156(12):1333-1343. doi: 10.1001/jamadermatol.2020.3260.

Helpful Links

• A Study of Baricitinib (LY3009104) in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 16, 2018
• Primary Completion (ACTUAL): July 29, 2019
• Study Completion (ACTUAL): August 22, 2019

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (ACTUAL): November 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 11, 2020
• Last Update Submitted That Met QC Criteria: July 24, 2020
• Last Verified: September 1, 2019

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: 17100; I4V-MC-JAIY (OTHER: Eli Lilly and Company); 2018-001726-26 (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