Clinical trial NCT03334396: A 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 Adult 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: 660
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, 2 mg, or 4 mg Baricitinib)
timeFrame: 16 Weeks
Secondary outcomes:
measure: Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1 mg 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 in 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 the Skin Pain Numeric Rating Scale (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 in 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: Praha 10
country: Czechia
facility: Clintrial, s.r.o.
state: Hl. M. Praha
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
state: Hl. M. Praha
city: Praha 5
country: Czechia
facility: Fakultni Nemocnice v Motole
state: Hl. M. Praha
city: Praha 8
country: Czechia
facility: Nemocnice Na Bulovce
state: Hl. M. Praha
city: Brno
country: Czechia
facility: Fakultni Nemocnice U svate Anny
state: Jihomoravský Kraj
city: Novy Jicin
country: Czechia
facility: Nemocnice Novy Jicin a.s.
state: Moravskoslezsky Kraj
city: Plzen, Jizni Predmesti
country: Czechia
facility: Fakultni Nemocnice Plzen
state: Plzensky Kraj
city: Kutna Hora
country: Czechia
facility: Kozni ambulance Kutna Hora, s.r.o.
state: Stredocesky Kraj
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem, o.z.
state: Ustecký Kraj
city: Aarhus
country: Denmark
facility: Aarhus Universitehospital Marselisborg Centret
city: Paris
country: France
facility: Hopital Saint-Louis
state: Cedex 10
city: Bordeaux Cedex
country: France
facility: CHU de Bordeaux Hopital Saint Andre
city: Brest
country: France
facility: CHRU de Brest - Hôpital Morvan
city: Grenoble Cédex 9
country: France
facility: CHU Grenoble Alpes
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: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Toulouse
country: France
facility: Hopital Larrey
city: Freiburg im Breisgau
country: Germany
facility: Universitätsklinikum Freiburg
state: Baden-Württemberg
city: München
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: Blankenfelde-Mahlow
country: Germany
facility: Gemeinschaftspraxis Mahlow
state: Brandenburg
city: Darmstadt
country: Germany
facility: Rosenpark Research Geschäftsbereich der Rosenparkklinik GmbH
state: Hessen
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
state: Hessen
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
state: Mecklenburg-Vorpommern
city: Bramsche
country: Germany
facility: Dermatologisches Zentrum Osnabrück Nord
state: Niedersachsen
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
state: Niedersachsen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: Nordrhein-Westfalen
city: Wuppertal
country: Germany
facility: Praxis Dr. Thomas Dirschka
state: Nordrhein-Westfalen
city: Magdeburg
country: Germany
facility: Universitätsklinikum Otto-von-Guericke-Universität
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Praxis Gerlach
state: Sachsen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Leipzig
country: Germany
facility: Universität Leipzig - Universitätsklinikum
state: Sachsen
city: Kiel
country: Germany
facility: Hautarztzentrum Kiel
state: Schleswig-Holstein
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Rothhaar Studien GmbH
city: Berlin
country: Germany
facility: ISA GmbH
city: Berlin
country: Germany
facility: Praxis für Ganzheitliche Dermatologie im Ärztehaus
city: Hamburg
country: Germany
facility: TFS Trial Form Support GmbH
city: Vizag
country: India
facility: King George Hospital
state: Andhra Pradesh
city: New Delhi
country: India
facility: All India Institue of Medical Sciences (AIIMS)
state: Delhi
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
city: Ahmedabad
country: India
facility: Panchshil Hospital
state: Gujarat
city: Ahmedabad
country: India
facility: Byramjee Jeejeebhoy Medical College & Civil Hospital
state: Gujarat
city: Bangalore
country: India
facility: M S Ramaiah Medical College Hospital
state: Karnataka
city: Navi Mumbai
country: India
facility: Dr. D. Y. Patil Medical College & Hospital
state: Maharashtra
city: Pune
country: India
facility: Jehangir Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Seth GS Medical College & KEM Hospital
state: Maharshtra
city: Chennai
country: India
facility: Chennai Meenakshi Multispeciality Hospital
state: Tamil Nadu
city: Secunderabad
country: India
facility: Gandhi Hospital
state: Telangana
city: Lucknow
country: India
facility: MV Hospital and Research Centre
state: Uttar Pradesh
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Pisa
country: Italy
facility: Azienda Ospedaliera - Universitaria Pisana
city: Roma
country: Italy
facility: Policlinico di Tor Vergata
city: Verona
country: Italy
facility: Ospedale Policlinico Giambattista Rossi, Borgo Roma
city: Ichikawa-shi
country: Japan
facility: Kawashima Dermatology Clinic
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Fumimori Clinic
state: Fukuoka
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima-ken
city: Nishi-ku, Yokohama-city
country: Japan
facility: Queen's Square Dermatology and Allergology
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Yokohama City Minato Red Cross Hospital
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Kyoto Prefectural University of Medicine
state: Kyoto
city: Nishi-ku Sakai-shi
country: Japan
facility: Kume Clinic
state: Osaka
city: Izumo
country: Japan
facility: Shimane University Hospital
state: Shimane
city: Hamamatsu-shi
country: Japan
facility: JA Shizuoka Kohseiren Enshu Hospital
state: Shizuoka
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: Shinagawa-KU
country: Japan
facility: NTT Medical Center Tokyo
state: Tokyo
city: Takaoka-shi
country: Japan
facility: Shirasaki Clinic
state: Toyama
city: Kofu
country: Japan
facility: Yamanashi Prefectural Central Hospital
state: Yamanashi
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Mexico City
country: Mexico
facility: Hospital de Jesus I.A.P.
state: Distrito Federal
city: México City
country: Mexico
facility: Grupo Médico CAMINO S.C.
state: Distrito Federal
city: Morella
country: Mexico
facility: Clínica Enfermedades Crónicas y Procedimientos Especiales SC
state: Michoacan
city: Monterrey
country: Mexico
facility: CRI Centro Regiomontano de Investigacion S.C.
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Hospital Univ. Dr. Jose Eleuterio Gonzalez
state: Nuevo León
city: Cuernavaca
country: Mexico
facility: JM Research S.C.
city: Distrito Federal
country: Mexico
facility: RM Pharma Specialists S.A. de C.V.
city: Durango
country: Mexico
facility: Instituto de Investigaciones Aplicadas a la Neurociencia A.C
city: Krasnodar
country: Russian Federation
facility: GBUZ Clinical dermatology and venereological dispensary
city: Moscow
country: Russian Federation
facility: State scientific centre for dermatovenerology and cosmetolog
city: Moscow
country: Russian Federation
facility: Russian state medical-stomatological university n.a. Evdokimov
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: Kaohsiung City
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: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Chang Gung Memorial Hospital - Taipei
city: Taoyuan City
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: 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: 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.