Clinical trial NCT03428100: 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
Official title: 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
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: 2018-02-09
Enrollment: 463
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 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.


Eligibility criteria: Inclusion Criteria:

* 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.

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 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.
* Have specific laboratory abnormalities related to thyroid, renal and liver function, or blood cells.
* Have received certain treatments that are contraindicated.
* Pregnant or breastfeeding.

Primary outcomes:
measure: Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)
timeFrame: Week 16
measure: Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement
timeFrame: Week 16
measure: Percentage of Participants Achieving EASI90
timeFrame: Week 16
measure: Percent Change From Baseline in 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 IGA of 0 or 1 With a >=2-point Improvement
timeFrame: Week 24
measure: Percentage of Participants Achieving EASI50
timeFrame: Week 16
measure: Percentage of Participants Achieving EASI75
timeFrame: Week 24
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 Number of Days Without Topical Corticosteroids (TCS) Use
timeFrame: Week 16
measure: Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)
timeFrame: Week 16
measure: Percent Change From Baseline in Itch NRS
timeFrame: Baseline, Week 16
measure: Percent Change From Baseline in Itch NRS at Week 24
timeFrame: Baseline, Week 24
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 in 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 in 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 European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)
timeFrame: Baseline, Week 16
measure: Percentage of Participants Achieving EASI75
timeFrame: Week 52
measure: Percent Change From Baseline in Itch NRS at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)
timeFrame: Week 68
measure: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)
timeFrame: Week 104
measure: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)
timeFrame: Week 68
measure: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)
timeFrame: Week 104
measure: Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)
timeFrame: Week 68
measure: Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)
timeFrame: Week 104
measure: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)
timeFrame: Week 68
measure: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)
timeFrame: Week 104
measure: Percentage of Participants With a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)
timeFrame: Week 68
measure: Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)
timeFrame: Week 104
measure: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 68 Participants Not Entered Into Substudy (All Participants)
timeFrame: Week 68
measure: Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 104 Participants Not Entered Into Substudy (All Participants)
timeFrame: Week 104
measure: Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)
timeFrame: Week 68
measure: Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 104 - Participants Not Entered Into Substudy (All Participants)
timeFrame: Week 104
measure: Percentage of Participants With A Response of EASI75 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)
timeFrame: Week 68
measure: Percentage of Participants With A Response of EASI75 Assessed at Week 104 - Participants Not Entered Into Substudy (All Participants)
timeFrame: Week 104
measure: Time to Retreatment (Time to IGA ≥3) Randomized Downtitration (All Patients Entering the Substudy)
timeFrame: Week 52 Up to Week 200
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitätsklinikum Graz
state: Steiermark
city: Innsbruck
country: Austria
facility: Universitätsklinik Innsbruck
state: Tyrol
city: Wien
country: Austria
facility: KA Rudolfstiftung
city: Wien
country: Austria
facility: AKH
city: Wien
country: Austria
facility: Sozialmed. Zentrum Ost - Donauspital
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Sint-Rafaël
city: Vitoria
country: Brazil
facility: Cedoes Centro Diagnostico Pequisa Osteoporose E Santo Ltd
state: ES
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento - Instituto de Educação e Pesquisa
state: Rio Grande Do Sul
city: Rio de Janeiro
country: Brazil
facility: CCBR Brasil Centro de Analises e Pesquisas Clínicas LTDA
state: RJ
city: Rio de Janeiro
country: Brazil
facility: IDERJ - Instituto de Dermatologia e Estética do Brasil
state: RJ
city: Campinas
country: Brazil
facility: Faculdade de Ciências Médicas - UNICAMP
state: Sao Paulo
city: Santo André
country: Brazil
facility: Fundação Faculdade de Medicina do ABC
state: Sao Paulo
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas da FMRP
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital da Clinicas da Faculdade de Medicina da USP
city: Tampere
country: Finland
facility: Terveystalo Tampere
state: Irkanmaa
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Turku
country: Finland
facility: Hospital Mehiläinen Neo
city: Rennes
country: France
facility: Hôpital de Pontchaillou
state: Cedex 9
city: Besancon Cedex
country: France
facility: CHU de Besancon Hopital Jean Minjoz
city: Bordeaux Cedex
country: France
facility: CHU de Bordeaux Hopital Saint Andre
city: Lille
country: France
facility: Hôpital C. HURIEZ
city: Mulhouse
country: France
facility: Hôpital Emile Muller
city: Nantes Cedex 1
country: France
facility: Chru De Nantes Hotel-Dieu
city: Nice cedex 3
country: France
facility: CHU de Nice Hopital de L'Archet
city: Toulon Cedex 9
country: France
facility: Hopital Sainte Anne (H.I.A)
city: Toulouse cedex 9
country: France
facility: Hopital Larrey
city: Valence
country: France
facility: Centre Hospitalier de Valence
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Stuttgart
country: Germany
facility: Hautarztpraxis Dr. Leitz und Kollegen
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: München
country: Germany
facility: Klinikum Rechts der Isar der TU München
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
state: Hessen
city: Buxtehude
country: Germany
facility: Elbe Kliniken Stade Buxtehude GmbH Klinikum Buxtehude
state: Niedersachsen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Osnabrück
country: Germany
facility: Klinische Forschung Osnabrück
state: Niedersachsen
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim
state: Nordrhein-Westfalen
city: Bochum
country: Germany
facility: St Josef-Hospital Bochum
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitätsklinikum Münster
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
state: Rheinland-Pfalz
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thüringen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg - Eppendorf
city: Milano
country: Italy
facility: Fondazione IRCCS Osp.Maggiore Policlinico - Dermatologia
state: Milan
city: San Donato Milanese
country: Italy
facility: Ospedale Clinicizzato San Donato
state: Milan
city: Roma
country: Italy
facility: Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
state: Rome
city: Ancona
country: Italy
facility: Azienda Ospedaliera Umberto I
city: Brescia
country: Italy
facility: Spedali Civili - Universita degli Studi
city: Chieti
country: Italy
facility: Fondazione Universitaria degli Studi G D'Annunzio
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia
city: Roma
country: Italy
facility: Policlinico di Tor Vergata
city: Verona
country: Italy
facility: Ospedale Policlinico Giambattista Rossi, Borgo Roma
city: Ainokawa, Ichikawa-shi
country: Japan
facility: Yanagihara dermatology clinic
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Fumimori Clinic
state: Fukuoka
city: Nishi-ku, Yokohama-city
country: Japan
facility: Queen's Square Dermatology and Allergology
state: Kanagawa
city: Kashima-machi, Kamimashiki-gun
country: Japan
facility: Noguchi Dermatology
state: Kumamoto
city: Neyagawa-shi
country: Japan
facility: Yoshioka Dermatology Clinic
state: Osaka
city: Nishi-ku Sakai-shi
country: Japan
facility: Kume Clinic
state: Osaka
city: Ohmiya-ku,Saitama-shi
country: Japan
facility: Sanrui Dermatology Clinic
state: Saitama
city: Chiyoda-ku
country: Japan
facility: Iidabashi Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Nihonbashi Sakura Clinic
state: Tokyo
city: Edogawa-ku
country: Japan
facility: Sumire Dermatology Clinic
state: Tokyo
city: Tachikawa-shi
country: Japan
facility: Tachikawa Dermatology Clinic
state: Tokyo
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Bergen op Zoom
country: Netherlands
facility: Bravis Ziekenhuis
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
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 Klinika Dermatologii
city: Osielsko
country: Poland
facility: DermoDent, Centrum Medyczne Czajkowscy
city: Szczecin
country: Poland
facility: LASER CLINIC Specjalistyczne Gabinety Lekarskie
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny CSK MON
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSW Klinika Dermatologii
city: Moscow
country: Russian Federation
facility: State scientific centre for dermatovenerology and cosmetolog
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University n.a. Sechenov
city: Saint-Petersburg
country: Russian Federation
facility: LLC ArsVitae NorthWest
city: Saint-Petersburg
country: Russian Federation
facility: LLC Medical Center "Kurator"
city: St. Petersburg
country: Russian Federation
facility: SPb SBHI Skin-venerologic dispensary #10
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Univ. Puerta de Hierro
state: Madrid
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Madrid
state: Madrid
city: Torrejón de Ardoz
country: Spain
facility: Hospital Universitario de Torrejon
state: Madrid
city: Manises
country: Spain
facility: Hospital de Manises
state: Valencia
city: Bilbao
country: Spain
facility: Hospital De Basurto
state: Vizcaya
city: Valencia
country: Spain
facility: Hospital Universitario Dr Pesset
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Sankt Gallen
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
state: Greater Manchester
city: Glasgow
country: United Kingdom
facility: West Glasgow Ambulatory Care Hospital
state: Lanarkshire
city: Leytonstone
country: United Kingdom
facility: Whipps Cross University Hospital
state: London
city: Liverpool
country: United Kingdom
facility: Broadgreen Hospital
state: Merseyside
city: London
country: United Kingdom
facility: Guys/St. Thomas Hospital
state: Surrey
city: Dudley
country: United Kingdom
facility: The Dudley Group NHS Foundation Trust
state: West Midlands
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: 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.