Clinical trial NCT03733301: A Study of Baricitinib (LY3009104) in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Combination With Topical Corticosteroids in Adult Patients With Moderate to Severe Atopic Dermatitis BREEZE-AD7
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atopic Dermatitis
Keywords: eczema
atopic eczema
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Incyte Corporation
First posted: 2018-11-07
Enrollment: 329
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* Have been diagnosed with moderate to severe atopic dermatitis for at least 12 months.
* Have had inadequate response to existing topical (applied to the skin) medications within 6 months preceding screening.
* Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period).
* Agree to use emollients daily.

Exclusion Criteria:

* Are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus), or a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections.
* A history of eczema herpeticum within 12 months, and/or a history of 2 or more episodes of eczema herpeticum in the past.
* Participants who are currently experiencing a skin infection that requires treatment, or is currently being treated, with topical or systemic antibiotics.
* Have any serious illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).
* Have been treated with the following therapies:

  * Monoclonal antibody for less than 5 half-lives prior to randomization.
  * Received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks prior to randomization.
  * Received any parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study.
  * Have had an intra-articular corticosteroid injection within 6 weeks prior to planned randomization.
* Have high blood pressure characterized by a repeated systolic blood pressure \>160 millimeters of mercury (mm Hg) or diastolic blood pressure \>100 mm Hg.
* Have had major surgery within the past eight weeks or are planning major surgery during the study.
* Have experienced any of the following within 12 weeks of screening: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
* Have a history of recurrent (≥2) VTE or are considered at high risk of VTE as deemed by the investigator.
* Have a history or presence of cardiovascular, respiratory, hepatic, chronic liver disease gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness.
* Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection including herpes zoster, tuberculosis.
* Have specific laboratory abnormalities.
* Have received certain treatments that are contraindicated.
* Pregnant or breastfeeding.

Primary outcomes:
measure: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)
timeFrame: Week 16
measure: Percentage of Participants Achieving EASI90
timeFrame: Week 16
measure: Percent Change From Baseline on EASI Score
timeFrame: Baseline, Week 16
measure: Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)
timeFrame: Week 16
measure: Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)
timeFrame: Week 16
measure: Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)
timeFrame: Baseline, Week 16
measure: Change From Baseline in Skin Pain NRS
timeFrame: Baseline, Week 16
measure: Percentage of Participants Achieving EASI50
timeFrame: Week 16
measure: Percentage of Participants Achieving IGA of 0
timeFrame: Week 16
measure: Change From Baseline in SCORAD
timeFrame: Baseline, Week 16
measure: Percentage of Participants Achieving SCORAD90
timeFrame: Week 16
measure: Change From Baseline in Body Surface Area (BSA) Affected
timeFrame: Baseline, Week 16
measure: Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment
timeFrame: Week 16
measure: Mean Gram Quantity of Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)
timeFrame: Week 0 through Week 16
measure: Percent Change From Baseline in Itch NRS
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score
timeFrame: Baseline, Week 16
measure: Change From Baseline on the Hospital Anxiety Depression Scale (HADS)
timeFrame: Baseline, Week 16
measure: Change From Baseline on the Dermatology Life Quality Index (DLQI)
timeFrame: Baseline, Week 16
measure: Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire
timeFrame: Baseline, Week 16
measure: Change From Baseline on the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm
timeFrame: Baseline, Week 16
measure: Change From Baseline on the EQ-5D-5L Visual Analog Scale (VAS)
timeFrame: Baseline, Week 16
measure: Mean Number of Days Without Use of Background TCS
timeFrame: Week 0 through Week 16
measure: Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement
timeFrame: Week 4
Other outcomes:
Locations:
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME) - Comite
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Fundacion CIDEA
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto de Neumonología y Dermatología
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Psoriahue Medicina Interdisciplinaria
city: Mendoza
country: Argentina
facility: Parra Dermatología
city: Phillip
country: Australia
facility: Woden Dermatology
state: Australian Capital Territory
city: Westmead
country: Australia
facility: Skin & Cancer Foundation Australia
state: New South Wales
city: Benowa
country: Australia
facility: The Skin Centre
state: Queensland
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research Pty Ltd
state: Queensland
city: Adelaide
country: Australia
facility: Clinical Trials SA Pty Ltd
state: South Australia
city: Melbourne
country: Australia
facility: Skin and Cancer Foundation Inc.
state: Victoria
city: Perth
country: Australia
facility: Fremantle Dermatology
state: Western Australia
city: Graz
country: Austria
facility: Universitätsklinikum Graz
state: Steiermark
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: München
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: Darmstadt
country: Germany
facility: Rosenpark Research Geschäftsbereich der Rosenparkklinik GmbH
state: Hessen
city: Bramsche
country: Germany
facility: Dermatologisches Zentrum Osnabrück Nord
state: Niedersachsen
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen - UKA
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitätsklinikum Münster
state: Nordrhein-Westfalen
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Hamburg
country: Germany
facility: TFS Trial Form Support GmbH
city: Roma
country: Italy
facility: Policlinico Univ. Agostino Gemelli
state: Lazio
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Genova
country: Italy
facility: Azienda Ospedaliera Universitaria Ospedale San Martino di Genova
city: Pisa
country: Italy
facility: Azienda Ospedaliera - Universitaria Pisana
city: Vicenza
country: Italy
facility: ULSS 8 UOC Dermatologia Viale Rodolfi, 37
city: Ichikawa-shi
country: Japan
facility: Kawashima Dermatology Clinic
state: Chiba
city: Matsudo-shi
country: Japan
facility: Medical Corporation Soleil Miyata Dermatology Clinic
state: Chiba
city: Dazaifu
country: Japan
facility: Yamano Dermatological Clinic
state: Fukuoka
city: Iizuka-city
country: Japan
facility: Tashiro Dermatological Clinic
state: Fukuoka
city: Sapporo
country: Japan
facility: Shibaki Dermatology Clinic
state: Hokkaido
city: Sapporo
country: Japan
facility: Sapporo Skin Clinic
state: Hokkaido
city: Nishi-ku, Yokohama-city
country: Japan
facility: Queen's Square Dermatology and Allergology
state: Kanagawa
city: Neyagawa-shi
country: Japan
facility: Yoshioka Dermatology Clinic
state: Osaka
city: Toyonaka-shi
country: Japan
facility: Senri-Chuo Hanafusa Dermatology Clinic
state: Osaka
city: Hamamatsu-shi
country: Japan
facility: JA Shizuoka Kohseiren Enshu Hospital
state: Shizuoka
city: Chiyoda-ku
country: Japan
facility: Iidabashi Clinic
state: Tokyo
city: Chiyoda-Ku
country: Japan
facility: Tokyo Teishin Hospital
state: Tokyo
city: Chuo-ku
country: Japan
facility: Hosono Clinic
state: Tokyo
city: Nerima-ku
country: Japan
facility: Oizumi Hanawa Clinic
state: Tokyo
city: Shinjuku
country: Japan
facility: Yamate Dermatological Clinic
state: Tokyo
city: Tachikawa-shi
country: Japan
facility: Tachikawa Dermatology Clinic
state: Tokyo
city: Takaoka-shi
country: Japan
facility: Shirasaki Clinic
state: Toyama
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
city: Goyang
country: Korea, Republic of
facility: Dongguk University Ilsan Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Konkuk University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Chungang University Hospital
city: Seoul
country: Korea, Republic of
facility: Hallym University Kangnam Sacred Heart Hospital
city: Lodz
country: Poland
facility: Dermed Centrum Medyczne Sp. z o.o.
city: Swidnik
country: Poland
facility: Lubelskie Centrum Diagnostyczne
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED
city: Warszawa
country: Poland
facility: Centrum Medyczne Evimed
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Cordoba
country: Spain
facility: Hospital Reina Sofia
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital De Gran Canaria Dr. Negrin
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung
city: New Taipei City
country: Taiwan
facility: Taipei Medical University- Shuang Ho Hospital
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Chang Gung Memorial Hospital - Taipei
city: Taoyuan, (r.o.c.)
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, Kaszuba A, Kolodsick J, Yang FE, Gamalo M, Brinker DR, DeLozier AM, Janes JM, Nunes FP, Thyssen JP, Simpson EL. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Dec 1;156(12):1333-1343. doi: 10.1001/jamadermatol.2020.3260.