Clinical trial NCT03334422: Study of Baricitinib (LY3009104) in Patients 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 Patients With Moderate to Severe Atopic Dermatitis
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: 2017-11-07
Enrollment: 615
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 as monotherapy 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 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.

Primary outcomes:
measure: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 2mg and 4mg Baricitinib)
timeFrame: 16 Weeks
Secondary outcomes:
measure: Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1mg Baricitinib)
timeFrame: 16 Weeks
measure: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)
timeFrame: 16 Weeks
measure: Percentage of Participants Achieving EASI90
timeFrame: 16 Weeks
measure: Percent Change From Baseline on EASI Score
timeFrame: Baseline, 16 Weeks
measure: Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)
timeFrame: 16 Weeks
measure: Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)
timeFrame: 16 Weeks
measure: Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)
timeFrame: Baseline, 16 Weeks
measure: Change From Baseline in Skin Pain NRS
timeFrame: Baseline, 16 Weeks
measure: Percentage of Participants Achieving EASI50
timeFrame: 16 Weeks
measure: Percentage of Participants Achieving IGA of 0
timeFrame: 16 Weeks
measure: Change From Baseline in SCORAD
timeFrame: Baseline, 16 Weeks
measure: Percentage of Participants Achieving SCORAD90
timeFrame: 16 Weeks
measure: Change From Baseline in Body Surface Area (BSA) Affected
timeFrame: Baseline, 16 Weeks
measure: Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment
timeFrame: 16 Weeks
measure: Percent Change From Baseline in Itch NRS
timeFrame: Baseline, 16 Weeks
measure: Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)
timeFrame: Baseline, 16 Weeks
measure: Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score
timeFrame: Baseline, 16 Weeks
measure: Change From Baseline on the Hospital Anxiety and Depression Scale (HADS)
timeFrame: Baseline, 16 Weeks
measure: Change From Baseline on the Dermatology Life Quality Index (DLQI)
timeFrame: Baseline, 16 Weeks
measure: Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire
timeFrame: Baseline, 16 Weeks
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, 16 Weeks
measure: Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)
timeFrame: Baseline, 16 Weeks
measure: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement
timeFrame: 4 Weeks
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: CENIT Centro de Neurociencias, Investigación y Tratamiento
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Clinica Adventista de Belgrano
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Fundacion CIDEA
city: Buenos Aires
country: Argentina
facility: Instituto de Neumonología y Dermatología
city: Buenos Aires
country: Argentina
facility: Psoriahue Medicina Interdisciplinaria
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Buenos Aires Skin
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: 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: Carlton
country: Australia
facility: Skin and Cancer Foundation Inc.
state: Victoria
city: Perth
country: Australia
facility: Fremantle Dermatology
state: Western Australia
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH - Elisabethinen
state: Oberösterreich
city: Wien
country: Austria
facility: KA Rudolfstiftung
city: Wien
country: Austria
facility: AKH
city: Wien
country: Austria
facility: KH Hietzing mit neurologischem Zentrum Rosenhügel
city: Wien
country: Austria
facility: Sozialmed. Zentrum Ost - Donauspital
city: Szeged
country: Hungary
facility: SZTE AOK Borgyogyaszati es Allergologiai Klinika
state: Csongrad
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Borgyogyaszati Klinika
state: Hajdu-Bihar
city: Puspokladany
country: Hungary
facility: Trial Pharma Kft.
state: Hajdu-Bihar
city: Szolnok
country: Hungary
facility: Allergo-Derm Bakos Kft
state: Jasz-Nagykun-Szolnok
city: Budapest
country: Hungary
facility: UNO Medical Trials Kft.
city: Kaposvar
country: Hungary
facility: Kaposi Mor Oktato Korhaz
city: Oroshaza
country: Hungary
facility: Oroshaza Varosi Onkormanyzat Korhaza
city: Szombathely
country: Hungary
facility: Markusovszky Korhaz
city: Veszprem
country: Hungary
facility: MedMare Bt
city: Afula
country: Israel
facility: Haemek Medical Center- Dermatology
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - Ein Karem
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Ainokawa, Ichikawa-shi
country: Japan
facility: Yanagihara dermatology clinic
state: Chiba
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Sapporo
country: Japan
facility: Sapporo Skin Clinic
state: Hokkaido
city: Inashiki-gun
country: Japan
facility: Tokyo Medical University Ibaraki Medical Center
state: Ibaraki
city: Yokohama-shi
country: Japan
facility: Nomura Dermatology Clinic
state: Kanagawa
city: Kashima-machi, Kamimashiki-gun
country: Japan
facility: Noguchi Dermatology
state: Kumamoto
city: Habikino
country: Japan
facility: Osaka Habikino Medical Center
state: Osaka
city: Neyagawa-shi
country: Japan
facility: Yoshioka Dermatology Clinic
state: Osaka
city: Ohmiya-ku,Saitama-shi
country: Japan
facility: Sanrui Dermatology Clinic
state: Saitama
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Chiyoda-Ku
country: Japan
facility: Tokyo Teishin Hospital
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Naoko Dermatology 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: Gifu
country: Japan
facility: Gifu University Hospital
city: Osaka
country: Japan
facility: Osaka City University Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University 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 of Medicine
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczna Przychodnia Dermatologiczna Specderm
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych, PI House
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Krakow
country: Poland
facility: Barbara Rewerska DIAMOND CLINIC
city: Lodz
country: Poland
facility: "Dermed" Centrum Medyczne Sp. z o.o.
city: Olsztyn
country: Poland
facility: Miejski Szpital Zespolony w Olsztynie
city: Osielsko
country: Poland
facility: DermoDent, Centrum Medyczne Czajkowscy
city: Szczecin
country: Poland
facility: LASER CLINIC S.C. Dr Tomasz Kochanowski, Dr Andrzej Krolicki
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSW
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Badalona
city: Fuenlabrada
country: Spain
facility: Hospital De Fuenlabrada
state: Madrid
city: Mostoles
country: Spain
facility: Hospital Universitario Rey Juan Carlos
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universitaria De Navarra
state: Navarra
city: Alicante
country: Spain
facility: Hospital General Universitario Alicante
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Pontevedra
country: Spain
facility: Centro de Especialidades Mollabao
city: Lausanne
country: Switzerland
facility: CHUV Centre Hospitalier Universitaire Vaudois
state: Vaud
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Genève
country: Switzerland
facility: HUG-Hôpitaux Universitaires de Genève
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
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: 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.
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, 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.