Study of Baricitinib (LY3009104) in Patients With Moderate to Severe Atopic Dermatitis (BREEZE-AD2)

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

The purpose of this study is to evaluate the efficacy and safety of baricitinib as monotherapy in participants with moderate to severe atopic dermatitis.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 615
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Fundacion Cidea
  • Buenos Aires, Argentina, C1425BEA
    • Instituto de Neumonologia y Dermatologia
  • Buenos Aires, Argentina, C1425DKG
    • Psoriahue Medicina Interdisciplinaria
  • Ciudad Autonoma Buenos Aires, Argentina, C1055AA0
    • Buenos Aires Skin
  • Mendoza, Argentina, 5500
    • Parra Dermatología
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1125ABD
      • CENIT Centro de Neurociencias, Investigación y Tratamiento
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1056ABJ
      • Centro de Investigaciones Metabólicas (CINME)
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, C1430EGF
      • Clinica Adventista de Belgrano
• 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
    • Woolloongabba, Queensland, Australia, 4102
      • Veracity Clinical Research Pty Ltd
  • South Australia
    • Adelaide, South Australia, Australia, 5073
      • Clinical Trials SA Pty Ltd
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • Skin and Cancer Foundation Inc.
  • Western Australia
    • Perth, Western Australia, Australia, 6160
      • Fremantle Dermatology
• Austria
  • Wien, Austria, 1220
    • Sozialmed. Zentrum Ost - Donauspital
  • Wien, Austria, 1090
    • AKH
  • Wien, Austria, 1030
    • KA Rudolfstiftung
  • Wien, Austria, 1130
    • KH Hietzing mit neurologischem Zentrum Rosenhügel
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4020
      • Ordensklinikum Linz GmbH - Elisabethinen
• Hungary
  • Budapest, Hungary, 1135
    • UNO Medical Trials Kft.
  • Kaposvar, Hungary, 7400
    • Kaposi Mór Oktató Kórház
  • Oroshaza, Hungary, 5901
    • Oroshaza Varosi Onkormanyzat Korhaza
  • Szombathely, Hungary, H-9700
    • Markusovszky Korhaz
  • Veszprem, Hungary, 8200
    • Medmare Bt
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • SZTE AOK Borgyogyaszati es Allergologiai Klinika
  • Hajdu-Bihar
    • Debrecen, Hajdu-Bihar, Hungary, 4032
      • Debreceni Egyetem Klinikai Kozpont Borgyogyaszati Klinika
    • Puspokladany, Hajdu-Bihar, Hungary, 4150
      • Trial Pharma Kft.
  • Jasz-Nagykun-Szolnok
    • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000
      • Allergo-Derm Bakos Kft
• Israel
  • Afula, Israel, 1834111
    • Haemek Medical Center- Dermatology
  • Haifa, Israel, 3525408
    • Rambam Medical Center
  • Jerusalem, Israel, 91220
    • Hadassah Medical Center - Ein Karem
  • Petach Tikva, Israel, 4941492
    • Rabin Medical Center
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Japan
  • Gifu, Japan, 501-1194
    • Gifu University Hospital
  • Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Chiba
    • Ainokawa, Ichikawa-shi, Chiba, Japan, 272-0143
      • Yanagihara dermatology clinic
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830 0011
      • Kurume University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0063
      • Sapporo Skin Clinic
  • Ibaraki
    • Inashiki-gun, Ibaraki, Japan, 300-0395
      • Tokyo Medical University Ibaraki Medical Center
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan, 221-0825
      • Nomura Dermatology Clinic
  • Kumamoto
    • Kashima-machi, Kamimashiki-gun, Kumamoto, Japan, 861-3101
      • Noguchi Dermatology
  • Osaka
    • Habikino, Osaka, Japan, 583-8588
      • Osaka Habikino Medical Center
    • Neyagawa-shi, Osaka, Japan, 572-0838
      • Yoshioka Dermatology Clinic
  • Saitama
    • Ohmiya-ku,Saitama-shi, Saitama, Japan, 330-0854
      • Sanrui Dermatology Clinic
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329-0498
      • Jichi Medical University Hospital
  • Tokyo
    • Chiyoda-Ku, Tokyo, Japan, 102-8798
      • Tokyo Teishin Hospital
    • Setagaya-ku, Tokyo, Japan, 158-0097
      • Naoko Dermatology Clinic
    • Shinjuku, Tokyo, Japan, 169-0075
      • Yamate Dermatological Clinic
    • Tachikawa-shi, Tokyo, Japan, 190-0023
      • Tachikawa Dermatology Clinic
• Korea, Republic of
  • 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
  • Seoul, Korea, Republic of, 07441
    • Hallym University of Medicine
  • Gyeonggi Do
    • Suwon, Gyeonggi Do, Korea, Republic of, 16499
      • Ajou University Hospital
  • Korea
    • Incheon, Korea, Korea, Republic of, 21565
      • Gachon University Gil Medical Center
• 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, 31-209
    • Barbara Rewerska Diamond Clinic
  • Lodz, Poland, 90-265
    • "DERMED" Centrum Medyczne Sp. z o.o.
  • Olsztyn, Poland, 10-229
    • Miejski Szpital Zespolony w Olsztynie
  • Osielsko, Poland, 86-031
    • DermoDent, Centrum Medyczne Czajkowscy
  • Szczecin, Poland, 70-332
    • LASER CLINIC S.C. Dr Tomasz Kochanowski, Dr Andrzej Krolicki
  • Warsaw, Poland, 04-141
    • Wojskowy Instytut Medyczny
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny MSW
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario Alicante
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28031
    • Hospital Infanta Leonor
  • Pontevedra, Spain, 36001
    • Centro de Especialidades Mollabao
  • Badalona
    • Barcelona, Badalona, Spain, 08916
      • Hospital Germans Trias i Pujol
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital De Fuenlabrada
    • Mostoles, Madrid, Spain, 28933
      • Hospital Universitario Rey Juan carlos
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clínica Universitaria de Navarra
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Genève, Switzerland, 1205
    • HUG-Hôpitaux Universitaires de Genève
  • Zürich, Switzerland, 8091
    • Universitätsspital Zürich
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • CHUV centre hospitalier universitaire vaudois

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 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 randomization.
  • 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 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 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 Milligram (mg) Baricitinib; 4mg Baricitinib administered orally once daily. Placebo 1 mg and 2 mg administered orally every day to match	Drug: Placebo; Administered orally; Drug: Baricitinib; Administered orally; Other Names: LY3009104
Experimental: 2mg Baricitinib; 2mg Baricitinib administered orally once daily. Placebo 1 mg and 4 mg administered orally every day to match.	Drug: Placebo; Administered orally; Drug: Baricitinib; Administered orally; Other Names: LY3009104
Experimental: 1mg Baricitinib; 1mg Baricitinib administered orally once daily. Placebo 2 mg and 4 mg administered orally every day to match.	Drug: Placebo; Administered orally; Drug: Baricitinib; Administered orally; Other Names: LY3009104
Placebo Comparator: Placebo; Placebo administered orally once daily.	Drug: Placebo; Administered orally

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 (Placebo, 2mg and 4mg Baricitinib)	The IGA measures the investigator's global assessment of the participants overall severity of their atopic dermatitis (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.	16 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)	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.	16 Weeks
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	Percentage of participants developing skin infections requiring antibiotic treatment.	16 Weeks
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1mg Baricitinib)	The IGA measures the investigator's global assessment of the participants 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.	16 Weeks
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 is 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.	16 Weeks
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 is 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.	16 Weeks
Percent Change From Baseline on EASI Score	The EASI assesses objective physician estimates of 2 dimensions of AD - 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, 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, 16 Weeks
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 VAS where 0 is no itching or no trouble sleeping and 10 is unbearable Itching or 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.	16 Weeks
Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)	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, 16 Weeks
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. LSMean was 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, 16 Weeks
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 EASI 50 is defined as ≥50% improvement from baseline in EASI score.	16 Weeks
Percentage of Participants Achieving IGA of 0	The IGA measures the investigator's global assessment of the participants 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.	16 Weeks
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 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. LSMeans was calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, 16 Weeks
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 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 defined as a ≥ 90% improvement from baseline in the SCORAD score.	16 Weeks
Change From Baseline in Body Surface Area (BSA) Affected	Body surface area 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. LSMean 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, 16 Weeks
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. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, 16 Weeks
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. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, 16 Weeks
Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score	The PGI-S-AD asked the participant to evaluate the severity of the disease at that point in time on a single-item, 5-point scale, using a daily diary. The same category labels used in the Physician's Global Assessment were used for the PGI-S-AD, ie, "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe." 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, 16 Weeks
Change From Baseline on the Hospital Anxiety and Depression Scale (HADS)	The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 items 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. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, 16 Weeks
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: 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 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. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, 16 Weeks
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. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, 16 Weeks
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm	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. A higher score indicates better health state. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, 16 Weeks
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. LSMean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, & treatment-by-visit-interaction as fixed categorical effects. Baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, 16 Weeks
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement	The IGA measures the investigator's global assessment of the participants 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.	4 Weeks

Collaborators and Investigators

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

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.
• Silverberg JI, DeLozier A, Sun L, Thyssen JP, Kim B, Yosipovitch G, Nunes FP, Gugiu PC, Doll HA, Eichenfield LF. Psychometric properties of the itch numeric rating scale, skin pain numeric rating scale, and atopic dermatitis sleep scale in adult patients with moderate-to-severe atopic dermatitis. Health Qual Life Outcomes. 2021 Oct 23;19(1):247. doi: 10.1186/s12955-021-01877-8.
• 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.
• 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, DeLozier AM, Nunes FP, Thyssen JP, Eichenfield LF, Wollenberg A, Ross Terres JA, Watts SD, Chen YF, Simpson EL, Silverberg JI. Baricitinib improves symptoms in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: patient-reported outcomes from two randomized monotherapy phase III trials. J Dermatolog Treat. 2022 May;33(3):1521-1530. doi: 10.1080/09546634.2020.1839008. Epub 2020 Nov 22.

Helpful Links

• A Study of Baricitinib (LY3009104) in Adults With Moderate to Severe Atopic Dermatitis (Eczema) (BREEZE-AD2)

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Actual): December 12, 2018
• Study Completion (Actual): December 12, 2018

Study Registration Dates

• First Submitted: November 3, 2017
• First Submitted That Met QC Criteria: November 3, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

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: 16581; I4V-MC-JAHM (Other Identifier: Eli Lilly and Company); 2017-000871-10 (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