A Study of Baricitinib (LY3009104) in Adult Participants With Moderate to Severe Atopic Dermatitis (BREEZE-AD5)

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 in adult 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): 440
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4X7
    • Centre de Recherche Dermatologique de Quebec Metropolitain
  • Richmond Hill, Canada, L4C 9M7
    • York Dermatology Center
  • Alberta
    • Calgary, Alberta, Canada, T2G 1B1
      • Kirk Barber Research
    • Calgary, Alberta, Canada, T3A 2N1
      • Institute For Skin Advancement
    • Edmonton, Alberta, Canada, T5K 1X3
      • Stratica Medical
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 0C6
      • Enverus Medical Research
    • Surrey, British Columbia, Canada, V3R 6A7
      • Dr. Chih-Ho Hong Medical Inc.
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Simcoderm Medical & Surgical Dermatology Centre
    • Etobicoke, Ontario, Canada, M8X 1Y9
      • Kingsway Clinical Research
    • Markham, Ontario, Canada, L3P1X2
      • Lynderm Research Inc
    • Niagara Falls, Ontario, Canada, L2H 1H5
      • Allergy Research Canada Inc.
    • Peterborough, Ontario, Canada, K9J 5K2
      • SKiN Centre for Dermatology
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • The Centre for Dermatology
    • Sudbury, Ontario, Canada, P3C 1X8
      • Medicor Research Inc
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research Inc
    • Windsor, Ontario, Canada, N8W 1E6
      • XLR8 Medical Research
  • Quebec
    • Montreal, Quebec, Canada, H2K4L5
      • Innovaderm Research Inc
• Puerto Rico
  • Caguas, Puerto Rico, 00727
    • Office of Dr. Samuel Sanchez PSC
  • Carolina, Puerto Rico, 00985
    • Office of Dr. Alma M. Cruz
  • Ponce, Puerto Rico, 00716
    • Ponce School of Medicine CAIMED Center
  • San Juan, Puerto Rico, 00917
    • GCM Medical Group PSC
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Johnson Dermatology
  • California
    • Beverly Hills, California, United States, 90211
      • Wallace Medical Group, Inc.
    • Encinitas, California, United States, 92024
      • California Dermatology and Clinical Research Institute
    • Fountain Valley, California, United States, 92708
      • Tien Q. Nguyen, MD inc. DBA First OC Dermatology
    • Fremont, California, United States, 94538
      • Center For Dermatology Clinical Research, Inc.
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine University of Southern California
    • Sacramento, California, United States, 95816
      • University of California Davis-Dermatology
    • San Diego, California, United States, 92108
      • Medical Center for Clinical Research
    • San Diego, California, United States, 92123
      • University Clinical Trials, Inc.
    • Santa Ana, California, United States, 92701
      • Southern California Dermatology
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
    • Walnut Creek, California, United States, 94598
      • Care Access Research-Walnut Creek
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Clinical Research Center of CT/NY
    • Farmington, Connecticut, United States, 06032
      • Univ of Connecticut
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • GWU/Medical Faculty Associates
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Solutions Through Advanced Research, Inc.
    • Largo, Florida, United States, 33770
      • Olympian Clinical Research
    • Miami, Florida, United States, 33173
      • Miami Dermatology & Laser Research
    • Pembroke Pines, Florida, United States, 33028
      • Riverchase Dermatology and Cosmetic Surgery
    • Tampa, Florida, United States, 33613
      • Forcare Clinical Research
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Macon, Georgia, United States, 31217
      • Dermatologic Surgery Specialists, PC
    • Sandy Springs, Georgia, United States, 30328
      • Advanced Medical Research
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research
  • Idaho
    • Boise, Idaho, United States, 83713
      • Treasure Valley Dermatology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Darien, Illinois, United States, 60561
      • University Dermatology
    • Rolling Meadows, Illinois, United States, 60008
      • Arlington Dermatology
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research
    • Plainfield, Indiana, United States, 46168
      • The Indiana Clinical Trials Center, PC
    • South Bend, Indiana, United States, 46617
      • The South Bend Clinic
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Dermatology Specialist
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Dermatology and Skin Cancer Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group, Inc.
    • Fort Gratiot, Michigan, United States, 48059
      • Hamzavi Dermatology
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Central Dermatology PC
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Skin Specialists, P.C
  • New York
    • New York, New York, United States, 10003
      • Icahn School of Medicine at Mount Sinai
    • Stony Brook, New York, United States, 11790
      • DermResearchCenter of New York, Inc
  • Ohio
    • Bexley, Ohio, United States, 43209
      • Bexley Dermatology Research
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Fairborn, Ohio, United States, 45324
      • Wright State Univ School of Medicine
    • Mason, Ohio, United States, 45040
      • Dermatologists of Southwest Ohio, Inc.
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology and Research Center
    • Portland, Oregon, United States, 97239
      • OHSU Center for Health and Healing
  • Pennsylvania
    • Exton, Pennsylvania, United States, 19341
      • Dermatology and Skin Surgery Center
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29407
      • Dermatology & Laser Center of Charleston
  • Texas
    • Bellaire, Texas, United States, 77401
      • Bellaire Dermatology
    • Dallas, Texas, United States, 75231
      • Modern Research Associates PLLC
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research, Inc.
    • San Antonio, Texas, United States, 78218
      • Texas Dermatology and Laser Specialists
    • Sugar Land, Texas, United States, 77497
      • Acclaim Dermatology, Pllc
  • Utah
    • Murray, Utah, United States, 84107
      • University of Utah MidValley Dematology
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System

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 a diagnosis of atopic dermatitis (AD) at least 12 months before screening.

• Have moderate to severe AD, including all of the following:

  • EASI score ≥16
  • IGA score of ≥3
  • ≥10% of BSA involvement
• 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 before randomization
  • received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks before randomization
  • received any parenteral corticosteroid administered by intramuscular or intravenous injection within 6 weeks of planned randomization or are anticipated to require parenteral injection of corticosteroids during the study
  • have had an intra-articular corticosteroid injection within 6 weeks of planned randomization
  • probenecid at the time of randomization that cannot be discontinued for the duration of the study
• 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: myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
• Have a history of venous thromboembolic event (VTE), or are considered at high risk for VTE.
• 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2 milligram (mg) Baricitinib; 2 mg Baricitinib administered orally every day. Placebo administered orally to maintain the blind.	Drug: Placebo; Administered orally; Drug: Baricitinib; Administered orally; Other Names: LY3009104
Experimental: 1 mg Baricitinib; 1 mg Baricitinib administered orally every day. Placebo administered orally to maintain the blind.	Drug: Placebo; Administered orally; Drug: Baricitinib; Administered orally; Other Names: LY3009104
Placebo Comparator: Placebo; Placebo administered orally every day.	Drug: Placebo; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (2 mg Baricitinib)	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving 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.	Week 16
Percentage of Participants Achieving EASI75 (1 mg Baricitinib)	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.	Week 16
Percentage of Participants Achieving EASI90	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.	Week 16
Percent Change From Baseline in EASI Score	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). Least Squares (LS) Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.	Week 16
Percentage of Participants Achieving a 4-Point Improvement on the 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.	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, Week 16
Change From Baseline in Skin Pain NRS	Skin Pain NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Percentage of of Participants Achieving EASI50	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in EASI score.	Week 16
Percentage of Participants Achieving IGA of 0	The IGA measures the investigator's global assessment of the participant's overall severity of their 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
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, baseline disease severity (IGA), visit and treatment-by-visit interaction as fixed categorial 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. SCORAD90 is defined as a ≥ 90% improvement from baseline in the SCORAD score.	Week 16
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 a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.	Baseline, Week 16
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	Percentage of participants developing skin infections requiring antibiotic treatment.	Week 16
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, baseline disease severity (IGA),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 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, 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 a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Change From Baseline on the 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 a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Change From Baseline on the Dermatology Life Quality Index (DLQI)	The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a little," "a lot," and "very much," with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or "not relevant" responses scored as "0." Scores range from 0 to 30 ("no impact on participant's life" to "extremely large effect on participant's life"), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA),visit, and treatment-by-visit-interaction as fixed categorical and baseline, and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Change From Baseline 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 Mean were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) 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 UK algorithm, with scores ranging from -0.594 to 1, and the US algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using a MMRM model with treatment, baseline disease activity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.	Baseline, Week 16
Change From Baseline 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 ranges 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 a MMRM model with treatment, baseline disease activity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.	Baseline, Week 16
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.	Week 4

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.
• Simpson EL, Bissonnette R, Paller AS, King B, Silverberg JI, Reich K, Thyssen JP, Doll H, Sun L, DeLozier AM, Nunes FP, Eichenfield LF. The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): a clinical outcome measure for the severity of atopic dermatitis. Br J Dermatol. 2022 Oct;187(4):531-538. doi: 10.1111/bjd.21615. Epub 2022 Aug 21.
• Rosmarin D, Casillas M, Chen S, Dawson Z, Pierce E, Zhang H, Bukhalo M, Smith S. Onset of Symptom Relief Reported in Daily Diaries of Patients With Atopic Dermatitis Treated With Baricitinib in a United States Clinical Trial (BREEZE-AD5). J Cutan Med Surg. 2022 May-Jun;26(3):262-266. doi: 10.1177/12034754211073661. Epub 2022 Jan 28.
• Silverberg JI, Boguniewicz M, Waibel J, Weisman J, Strowd L, Sun L, Ding Y, Feely M, Nunes FP, Simpson EL. Clinical Tailoring of Baricitinib 2 mg in Atopic Dermatitis: Baseline Body Surface Area and Rapid Onset of Action Identifies Response at Week 16. Dermatol Ther (Heidelb). 2022 Jan;12(1):137-148. doi: 10.1007/s13555-021-00640-7. Epub 2021 Nov 30.
• 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.

Helpful Links

• A Study of Baricitinib (LY3009104) in Adult Participants With Moderate to Severe Atopic Dermatitis (Eczema) (BREEZE-AD5)

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Actual): December 9, 2019
• Study Completion (Actual): August 16, 2021

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): September 9, 2022
• Last Update Submitted That Met QC Criteria: August 11, 2022
• Last Verified: August 1, 2022

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: 17049; I4V-MC-JAIW (Other Identifier: Eli Lilly and Company)

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; Statistical Analysis Plan (SAP); Clinical Study Report (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