A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis That Are Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Advisable
BREEZE-AD4
A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety and Efficacy of Baricitinib in Combination With Topical Corticosteroids in Adult Patients With Moderate-to-Severe Atopic Dermatitis Who Have Experienced Failure to Cyclosporine or Are Intolerant to, or Have Contraindication to, Cyclosporine
3 other identifiers
interventional
463
14 countries
103
Brief Summary
The purpose of this study is to determine the efficacy and safety of baricitinib in combination with topical corticosteroids in participants with moderate to severe atopic dermatitis who have experienced failure to cyclosporine or are intolerant to, or have contraindication to cyclosporine.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2018
Longer than P75 for phase_3
103 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 5, 2018
CompletedFirst Posted
Study publicly available on registry
February 9, 2018
CompletedStudy Start
First participant enrolled
May 15, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 25, 2019
CompletedResults Posted
Study results publicly available
January 19, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 20, 2023
CompletedMay 14, 2024
April 15, 2024
1.5 years
February 5, 2018
November 26, 2020
April 18, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Week 16
Secondary Outcomes (46)
Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)
Week 16
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement
Week 16
Percentage of Participants Achieving EASI90
Week 16
Percent Change From Baseline in EASI Score
Baseline, Week 16
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)
Week 16
- +41 more secondary outcomes
Study Arms (19)
4 mg Baricitinib
EXPERIMENTAL4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
2 mg Baricitinib
EXPERIMENTAL2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
1 mg Baricitinib
EXPERIMENTAL1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Placebo
PLACEBO COMPARATORPlacebo administered orally once daily in combination with topical corticosteroids. Additional Placebo administered orally to maintain the blind.
Long Term Extension(LTE) Substudy 4mg Baricitinib to 4mg Baricitinib (Responders/Partial Responders)
EXPERIMENTAL4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)
EXPERIMENTAL4 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)
EXPERIMENTAL2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib (Responders/Partial Responders)
EXPERIMENTAL2 mg Baricitinib rerandomized to 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 4 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy
EXPERIMENTAL4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy
EXPERIMENTAL2 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy
EXPERIMENTAL1 mg administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo (Responders/Partial Responders) - Did Not Enter Substudy
PLACEBO COMPARATORPlacebo administered orally once daily (continued previous dose) in combination with topical corticosteroids. Additional placebo administered orally to maintain the blind.
LTE 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy
EXPERIMENTAL4 mg administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy
EXPERIMENTAL2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy
EXPERIMENTAL2 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy
EXPERIMENTAL1 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy
EXPERIMENTAL1 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy
EXPERIMENTALPlacebo rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy
EXPERIMENTALPlacebo rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Interventions
Administered orally.
Administered orally.
Administered as standard-of-care.
Eligibility Criteria
You may qualify if:
- Have been diagnosed with moderate to severe Atopic Eczema (Atopic Dermatitis) for at least 12 months.
- Have had inadequate response to existing topical (applied to the skin) medications within 6 months preceding screening.
- Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period).
- Agree to use emollients daily.
- Have a medical contraindication to cyclosporine, or had intolerance and/or unacceptable toxicity or inadequate response to cyclosporine in the past.
You may not qualify if:
- Are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus), or a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections.
- A history of eczema herpeticum within 12 months, and/or a history of 2 or more episodes of eczema herpeticum in the past.
- Participants who are currently experiencing a skin infection that requires treatment, or are currently being treated, with topical or systemic antibiotics.
- Have any serious illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).
- Have been treated with the following therapies:
- Monoclonal antibody for less than 5 half-lives prior to randomization.
- Received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks prior to randomization.
- Received oral corticosteroids within 4 weeks prior to randomization or parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study.
- Have had an intra-articular corticosteroid injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization.
- Have high blood pressure characterized by a repeated systolic blood pressure \>160 millimeters of mercury (mm Hg) or diastolic blood pressure \>100 mm Hg.
- Have had major surgery within the past eight weeks or are planning major surgery during the study.
- Have experienced any of the following within 12 weeks of screening: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
- Have a history of recurrent (≥ 2) VTE or are considered at high risk of VTE as deemed by the investigator.
- Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness.
- Have a current or recent and/or clinically serious viral, bacterial, fungal, or parasitic infection including but not limited to herpes zoster, tuberculosis.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eli Lilly and Companylead
- Incyte Corporationcollaborator
Study Sites (103)
Universitätsklinikum Graz
Graz, Styria, 8036, Austria
Universitätsklinik Innsbruck
Innsbruck, Tyrol, 6020, Austria
KA Rudolfstiftung
Vienna, 1030, Austria
AKH
Vienna, 1090, Austria
Sozialmed. Zentrum Ost - Donauspital
Vienna, 1220, Austria
Universitair Ziekenhuis Brussel
Brussels, 1090, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
UZ Leuven - Campus Sint-Rafaël
Leuven, 3000, Belgium
Cedoes Centro Diagnostico Pequisa Osteoporose E Santo Ltd
Vitória, Espírito Santo, 29055 450, Brazil
CCBR Brasil Centro de Analises e Pesquisas Clínicas LTDA
Rio de Janeiro, Rio de Janeiro, 22271-100, Brazil
IDERJ - Instituto de Dermatologia e Estética do Brasil
Rio de Janeiro, Rio de Janeiro, 22470-220, Brazil
Irmandade da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90020-090, Brazil
Hospital Moinhos de Vento - Instituto de Educação e Pesquisa
Porto Alegre, Rio Grande do Sul, 90560-030, Brazil
Faculdade de Ciências Médicas - UNICAMP
Campinas, São Paulo, 13083-887, Brazil
Hospital das Clinicas da FMRP
Ribeirão Preto, São Paulo, 14048-900, Brazil
Fundação Faculdade de Medicina do ABC
Santo André, São Paulo, 09060-650, Brazil
Hospital da Clinicas da Faculdade de Medicina da USP
São Paulo, 05403-000, Brazil
Terveystalo Tampere
Tampere, Irkanmaa, 33100, Finland
Helsinki University Central Hospital
Helsinki, 00250, Finland
Hospital Mehiläinen Neo
Turku, 20520, Finland
Hôpital de Pontchaillou
Rennes, Cedex 9, 35033, France
CHU de Besancon Hopital Jean Minjoz
Besançon, 25030, France
CHU de Bordeaux Hopital Saint Andre
Bordeaux, 33075, France
Hôpital C. HURIEZ
Lille, 59037, France
Hôpital Emile Muller
Mulhouse, 68100, France
Chru De Nantes Hotel-Dieu
Nantes, 44093, France
CHU de Nice Hopital de L'Archet
Nice, 06202, France
Hopital Sainte Anne (H.I.A)
Toulon, 83800, France
Hopital Larrey
Toulouse, 31059, France
Centre Hospitalier de Valence
Valence, 26953, France
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120, Germany
Hautarztpraxis Dr. Leitz und Kollegen
Stuttgart, Baden-Wurttemberg, 70178, Germany
Universitätsklinikum Erlangen
Erlangen, Bavaria, 91054, Germany
Klinikum Rechts der Isar der TU München
München, Bavaria, 80802, Germany
Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
Frankfurt am Main, Hesse, 60590, Germany
Elbe Kliniken Stade Buxtehude GmbH Klinikum Buxtehude
Buxtehude, Lower Saxony, 21614, Germany
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30449, Germany
Klinische Forschung Osnabrück
Osnabrück, Lower Saxony, 49074, Germany
Fachklinik Bad Bentheim
Bad Bentheim, North Rhine-Westphalia, 48455, Germany
St Josef-Hospital Bochum
Bochum, North Rhine-Westphalia, 44791, Germany
Universitätsklinikum Bonn
Bonn, North Rhine-Westphalia, 53127, Germany
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45147, Germany
Universitätsklinikum Münster
Münster, North Rhine-Westphalia, 48149, Germany
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
Mainz, Rhineland-Palatinate, 55131, Germany
Universitätsklinikum Jena
Jena, Thuringia, 07743, Germany
Charité Universitätsmedizin Berlin
Berlin, 10117, Germany
Universitätsklinikum Hamburg - Eppendorf
Hamburg, 20246, Germany
Fondazione IRCCS Osp.Maggiore Policlinico - Dermatologia
Milan, Milan, 20122, Italy
Ospedale Clinicizzato San Donato
San Donato Milanese, Milan, 20097, Italy
Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
Roma, Rome, 00161, Italy
Azienda Ospedaliera Umberto I
Ancona, 60020, Italy
Spedali Civili - Universita degli Studi
Brescia, 25123, Italy
Fondazione Universitaria degli Studi G D'Annunzio
Chieti, 66100, Italy
Azienda Ospedaliera di Perugia
Perugia, 06129, Italy
Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia
Reggio Emilia, 42123, Italy
Policlinico di Tor Vergata
Roma, 00133, Italy
Ospedale Policlinico Giambattista Rossi, Borgo Roma
Verona, 37134, Italy
Yanagihara dermatology clinic
Ainokawa, Ichikawa-shi, Chiba, 272-0143, Japan
Fumimori Clinic
Fukuoka, Fukuoka, 815-0082, Japan
Queen's Square Dermatology and Allergology
Nishi-ku, Yokohama-city, Kanagawa, 220-6208, Japan
Noguchi Dermatology
Kashima-machi, Kamimashiki-gun, Kumamoto, 861-3101, Japan
Yoshioka Dermatology Clinic
Neyagawa, Osaka, 572-0838, Japan
Kume Clinic
Nishi-ku Sakai-shi, Osaka, 593-8324, Japan
Sanrui Dermatology Clinic
Ohmiya-ku,Saitama-shi, Saitama, 330-0854, Japan
Iidabashi Clinic
Chiyoda-ku, Tokyo, 102-0072, Japan
Nihonbashi Sakura Clinic
Chuo-ku, Tokyo, 103-0025, Japan
Sumire Dermatology Clinic
Edogawa-ku, Tokyo, 133-0057, Japan
Tachikawa Dermatology Clinic
Tachikawa-shi, Tokyo, 190-0023, Japan
Academisch Medisch Centrum
Amsterdam, 1105 AZ, Netherlands
Bravis Ziekenhuis
Bergen op Zoom, 4624 VT, Netherlands
Amphia Ziekenhuis
Breda, 4818 CK, Netherlands
NZOZ Specjalistyczna Przychodnia Dermatologiczna Specderm
Bialystok, 15-375, Poland
Centrum Badan Klinicznych, PI House
Gdansk, 80-546, Poland
Centrum Medyczne Angelius Provita
Katowice, 40-611, Poland
Barbara Rewerska DIAMOND CLINIC
Krakow, 31-559, Poland
Dermed Centrum Medyczne Sp. z o.o.
Lodz, 90-265, Poland
Miejski Szpital Zespolony w Olsztynie Klinika Dermatologii
Olsztyn, 10-229, Poland
DermoDent, Centrum Medyczne Czajkowscy
Osielsko, 86-031, Poland
LASER CLINIC Specjalistyczne Gabinety Lekarskie
Szczecin, 70-332, Poland
Centralny Szpital Kliniczny MSW Klinika Dermatologii
Warsaw, 02-507, Poland
Wojskowy Instytut Medyczny CSK MON
Warsaw, 04-141, Poland
State scientific centre for dermatovenerology and cosmetolog
Moscow, 107076, Russia
First Moscow State Medical University n.a. Sechenov
Moscow, 119991, Russia
SPb SBHI Skin-venerologic dispensary #10
Saint Petersburg, 194021, Russia
LLC ArsVitae NorthWest
Saint Petersburg, 194223, Russia
LLC Medical Center "Kurator"
Saint Petersburg, 196240, Russia
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Hospital Univ. Puerta de Hierro
Majadahonda, Madrid, 28220, Spain
Hospital Universitario Quiron Madrid
Pozuelo de Alarcón, Madrid, 28223, Spain
Hospital Universitario de Torrejon
Torrejón de Ardoz, Madrid, 28850, Spain
Hospital de Manises
Manises, Valencia, 46940, Spain
Hospital De Basurto
Bilbao, Vizcaya, 48013, Spain
Hospital Universitario Dr Pesset
Valencia, 46017, Spain
Kantonsspital St. Gallen
Sankt Gallen, Canton of St. Gallen, 9007, Switzerland
Inselspital Bern
Bern, 3010, Switzerland
Universitätsspital Zürich
Zurich, 8091, Switzerland
Salford Royal NHS Foundation Trust
Salford, Greater Manchester, M6 8HD, United Kingdom
West Glasgow Ambulatory Care Hospital
Glasgow, Lanarkshire, G3 8SJ, United Kingdom
Whipps Cross University Hospital
Leytonstone, London, E11 1NR, United Kingdom
Broadgreen Hospital
Liverpool, Merseyside, L14 3LB, United Kingdom
Guys/St. Thomas Hospital
London, Surrey, SE1 9RT, United Kingdom
The Dudley Group NHS Foundation Trust
Dudley, West Midlands, DY1 2HQ, United Kingdom
Related Publications (2)
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.
PMID: 36255569DERIVEDKing 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.
PMID: 33826132DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2018
First Posted
February 9, 2018
Study Start
May 15, 2018
Primary Completion
November 25, 2019
Study Completion
April 20, 2023
Last Updated
May 14, 2024
Results First Posted
January 19, 2021
Record last verified: 2024-04-15
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
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.