A Study of Baricitinib (LY3009104) in Patients With Moderate to Severe Atopic Dermatitis (BREEZE-AD1)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult 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): 660
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Hl. M. Praha
    • Praha 10, Hl. M. Praha, Czechia, 100 00
      • CLINTRIAL, s.r.o.
    • Praha 10, Hl. M. Praha, Czechia, 100 34
      • Fakultni nemocnice Kralovske Vinohrady
    • Praha 5, Hl. M. Praha, Czechia, 150 06
      • Fakultni nemocnice v Motole
    • Praha 8, Hl. M. Praha, Czechia, 180 81
      • Nemocnice Na Bulovce
  • Jihomoravský Kraj
    • Brno, Jihomoravský Kraj, Czechia, 656 91
      • Fakultni Nemocnice U svate Anny
  • Moravskoslezsky Kraj
    • Novy Jicin, Moravskoslezsky Kraj, Czechia, 741 01
      • Nemocnice Novy Jicin a.s.
  • Plzensky Kraj
    • Plzen, Jizni Predmesti, Plzensky Kraj, Czechia, 301 00
      • Fakultní nemocnice Plzen
  • Stredocesky Kraj
    • Kutna Hora, Stredocesky Kraj, Czechia, 28401
      • Kozni ambulance Kutna Hora, s.r.o.
  • Ustecký Kraj
    • Usti nad Labem, Ustecký Kraj, Czechia, 40113
      • Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem, o.z.
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus Universitehospital Marselisborg Centret
• France
  • Bordeaux Cedex, France, 33075
    • CHU de Bordeaux Hôpital Saint André
  • Brest, France, 29200
    • CHRU de Brest - Hôpital Morvan
  • Grenoble Cédex 9, France, 38043
    • CHU Grenoble Alpes
  • Nantes Cedex 1, France, 44093
    • Chru De Nantes Hotel-Dieu
  • Nice cedex 3, France, 06202
    • Chu de Nice Hopital de L'Archet
  • Pierre Benite Cedex, France, 69495
    • Centre Hospitalier Lyon Sud
  • Toulouse, France, 31059
    • Hopital Larrey
  • Cedex 10
    • Paris, Cedex 10, France, 75475
      • Hôpital Saint-Louis
• Germany
  • Berlin, Germany, 10789
    • ISA GmbH
  • Berlin, Germany, 10783
    • Rothhaar Studien GmbH
  • Berlin, Germany, 13055
    • Praxis für Ganzheitliche Dermatologie im Ärztehaus
  • Hamburg, Germany, 20537
    • TFS Trial Form Support GmbH
  • Baden-Württemberg
    • Freiburg im Breisgau, Baden-Württemberg, Germany, 79104
      • Universitatsklinikum Freiburg
  • Bayern
    • München, Bayern, Germany, 80337
      • Klinikum der Universität München
  • Brandenburg
    • Blankenfelde-Mahlow, Brandenburg, Germany, 15831
      • Gemeinschaftspraxis Mahlow
  • Hessen
    • Darmstadt, Hessen, Germany, 64283
      • Rosenpark Research Geschäftsbereich der Rosenparkklinik GmbH
    • Frankfurt am Main, Hessen, Germany, 60590
      • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18057
      • Universitatsmedizin Rostock
  • Niedersachsen
    • Bramsche, Niedersachsen, Germany, 49565
      • Dermatologisches Zentrum Osnabrück Nord
    • Göttingen, Niedersachsen, Germany, 37075
      • Universitatsmedizin Gottingen
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53127
      • Universitatsklinikum Bonn
    • Wuppertal, Nordrhein-Westfalen, Germany, 42287
      • Praxis Dr. Thomas Dirschka
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitätsklinikum Carl Gustav Carus
    • Dresden, Sachsen, Germany, 01097
      • Praxis Gerlach
    • Leipzig, Sachsen, Germany, 04103
      • Universität Leipzig - Universitätsklinikum
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39120
      • Universitätsklinikum Otto-von-Guericke-Universität
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitätsklinikum Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24103
      • Hautarztzentrum Kiel
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitätsklinikum Schleswig-Holstein
• India
  • Andhra Pradesh
    • Vizag, Andhra Pradesh, India, 530002
      • King George Hospital
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Sir Ganga Ram Hospital
    • New Delhi, Delhi, India, 110 029
      • All India Institue of Medical Sciences (AIIMS)
  • Gujarat
    • Ahmedabad, Gujarat, India, 380005
      • Panchshil Hospital
    • Ahmedabad, Gujarat, India, 380016
      • Byramjee Jeejeebhoy Medical College & Civil Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • M S Ramaiah Medical College Hospital
  • Maharashtra
    • Navi Mumbai, Maharashtra, India, 400706
      • Dr. D. Y. Patil Medical College & Hospital
    • Pune, Maharashtra, India, 411001
      • Jehangir Hospital
  • Maharshtra
    • Mumbai, Maharshtra, India, 400012
      • Seth GS Medical College & KEM Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600004
      • Chennai Meenakshi Multispeciality Hospital
  • Telangana
    • Secunderabad, Telangana, India, 500003
      • Gandhi Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226003
      • MV Hospital and Research Centre
• Italy
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Pisa, Italy, 56126
    • Azienda Ospedaliera - Universitaria Pisana
  • Roma, Italy, 00133
    • Policlinico di Tor Vergata
  • Verona, Italy, 37134
    • Ospedale Policlinico Giambattista Rossi, Borgo Roma
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Chiba
    • Ichikawa-shi, Chiba, Japan, 272-0033
      • Kawashima Dermatology Clinic
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 815-0082
      • Fumimori Clinic
  • Hiroshima-ken
    • Hiroshima-shi, Hiroshima-ken, Japan, 734-8551
      • Hiroshima University Hospital
  • Kanagawa
    • Nishi-ku, Yokohama-city, Kanagawa, Japan, 220-6208
      • Queen's Square Dermatology and Allergology
    • Yokohama-shi, Kanagawa, Japan, 231-8682
      • Yokohama City Minato Red Cross Hospital
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • Kyoto Prefectural University of Medicine
  • Osaka
    • Nishi-ku Sakai-shi, Osaka, Japan, 593-8324
      • Kume Clinic
  • Shimane
    • Izumo, Shimane, Japan, 693-8501
      • Shimane University Hospital
  • Shizuoka
    • Hamamatsu-shi, Shizuoka, Japan, 430-0929
      • JA Shizuoka Kohseiren Enshu Hospital
  • 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
    • Shinagawa-KU, Tokyo, Japan, 141-8625
      • NTT Medical Center Tokyo
  • Toyama
    • Takaoka-shi, Toyama, Japan, 9330871
      • Shirasaki Clinic
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-8506
      • Yamanashi Prefectural Central Hospital
• Mexico
  • Cuernavaca, Mexico, 62290
    • JM Research S.C.
  • Distrito Federal, Mexico, 3100
    • RM Pharma Specialists S.A. de C.V.
  • Durango, Mexico, 34000
    • Instituto de Investigaciones Aplicadas a la Neurociencia A.C
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 06090
      • Hospital de Jesus I.A.P.
    • México City, Distrito Federal, Mexico, 03310
      • Grupo Médico Camino S.C.
  • Michoacan
    • Morella, Michoacan, Mexico, 58249
      • Clínica Enfermedades Crónicas y Procedimientos Especiales SC
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64060
      • CRI Centro Regiomontano de Investigacion S.C.
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Univ. Dr. Jose Eleuterio Gonzalez
• Russian Federation
  • Krasnodar, Russian Federation, 350020
    • GBUZ Clinical dermatology and venereological dispensary
  • Moscow, Russian Federation, 107076
    • State scientific centre for dermatovenerology and cosmetolog
  • Moscow, Russian Federation, 111398
    • Russian state medical-stomatological university n.a. Evdokimov
  • 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
• Taiwan
  • Kaohsiung City, 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
  • Tainan City, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei City, Taiwan, 10048
    • National Taiwan University Hospital
  • Taipei City, Taiwan, 10508
    • Chang Gung Memorial Hospital - Taipei
  • Taoyuan City, Taiwan, 33305
    • 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 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
• Masking: DOUBLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 4 milligram (mg) Baricitinib; 4 mg 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: 2 mg Baricitinib; 2 mg 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: 1 mg Baricitinib; 1 mg 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.
EXPERIMENTAL: 4 mg Baricitinib Maximum Extended Enrollment Cohort; 4 mg 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: 2 mg Baricitinib Maximum Extended Enrollment Cohort; 2 mg 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: 1 mg Baricitinib Maximum Extended Enrollment Cohort; 1 mg 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 Maximum Extended Enrollment Cohort; 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, 2 mg, or 4 mg Baricitinib)	The IGA measures the investigator's 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) 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 IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1 mg Baricitinib)	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.	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 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.	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 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.	16 Weeks
Percent Change From Baseline in 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 was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). Least Square (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 effect	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 visual analog scale (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.	16 Weeks
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
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 the Skin Pain Numeric Rating Scale (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 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
Percentage of Participants Achieving EASI50	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in EASI score.	16 Weeks
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.	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 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, 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 a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. SCORAD90 is defined as a ≥ 90% improvement from baseline in the SCORAD score.	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. 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, 16 Weeks
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	Percentage of participants developing skin infections requiring antibiotic treatment.	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. 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 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 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 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, i.e., "(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 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 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 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 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 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 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 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, 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, 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. 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, 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 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.	4 Weeks

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.
• 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.
• 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.
• 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-AD1)

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 23, 2017
• Primary Completion (ACTUAL): December 6, 2018
• Study Completion (ACTUAL): August 16, 2019

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): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 7, 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: 16580; I4V-MC-JAHL (OTHER: Eli Lilly and Company); 2017-000870-12 (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