Clinical trial NCT03435081: A Study of Baricitinib (LY3009104) in Adult Participants 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: 2018-02-15
Enrollment: 440
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 adult participants with moderate to severe atopic dermatitis.


Eligibility criteria: Inclusion Criteria:

* Have a diagnosis of atopic dermatitis (AD) at least 12 months before screening.
* Have moderate to severe AD, including all of the following:

  * EASI score ≥16
  * IGA score of ≥3
  * ≥10% of BSA involvement
* 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 before randomization
  * received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks before randomization
  * received any parenteral corticosteroid administered by intramuscular or intravenous injection within 6 weeks of planned randomization or are anticipated to require parenteral injection of corticosteroids during the study
  * have had an intra-articular corticosteroid injection within 6 weeks of planned randomization
  * probenecid at the time of randomization that cannot be discontinued for the duration of the study
* 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: myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
* Have a history of venous thromboembolic event (VTE), or are considered at high risk for VTE.
* 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 Eczema Area and Severity Index 75 (EASI75) (2 mg Baricitinib)
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement
timeFrame: Week 16
measure: Percentage of Participants Achieving EASI75 (1 mg Baricitinib)
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 on the 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, Week 16
measure: Change From Baseline in Skin Pain NRS
timeFrame: Baseline, Week 16
measure: Percentage of 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: 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 (US) and United Kingdom (UK) 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 Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement
timeFrame: Week 4
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Fort Smith
country: United States
facility: Johnson Dermatology
state: Arkansas
city: Beverly Hills
country: United States
facility: Wallace Medical Group, Inc.
state: California
city: Encinitas
country: United States
facility: California Dermatology and Clinical Research Institute
state: California
city: Fountain Valley
country: United States
facility: Tien Q. Nguyen, MD inc. DBA First OC Dermatology
state: California
city: Fremont
country: United States
facility: Center for Dermatology Clinical Research, Inc.
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine University of Southern California
state: California
city: Sacramento
country: United States
facility: University of California Davis-Dermatology
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: San Diego
country: United States
facility: University Clinical Trials, Inc.
state: California
city: Santa Ana
country: United States
facility: Southern California Dermatology
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Walnut Creek
country: United States
facility: Care Access Research-Walnut Creek
state: California
city: Danbury
country: United States
facility: Clinical Research Center of CT/NY
state: Connecticut
city: Farmington
country: United States
facility: Univ of Connecticut
state: Connecticut
city: Washington
country: United States
facility: GWU/Medical Faculty Associates
state: District of Columbia
city: Jacksonville
country: United States
facility: Solutions Through Advanced Research, Inc.
state: Florida
city: Largo
country: United States
facility: Olympian Clinical Research
state: Florida
city: Miami
country: United States
facility: Miami Dermatology & Laser Research
state: Florida
city: Pembroke Pines
country: United States
facility: Riverchase Dermatology and Cosmetic Surgery
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: Macon
country: United States
facility: Dermatologic Surgery Specialists, PC
state: Georgia
city: Sandy Springs
country: United States
facility: Advanced Medical Research
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research
state: Georgia
city: Boise
country: United States
facility: Treasure Valley Dermatology
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Darien
country: United States
facility: University Dermatology
state: Illinois
city: Rolling Meadows
country: United States
facility: Arlington Dermatology
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research
state: Indiana
city: Plainfield
country: United States
facility: The Indiana Clinical Trials Center, PC
state: Indiana
city: South Bend
country: United States
facility: The South Bend Clinic
state: Indiana
city: Louisville
country: United States
facility: Dermatology Specialist
state: Kentucky
city: Rockville
country: United States
facility: Dermatology and Skin Cancer Specialists
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Bay City
country: United States
facility: Great Lakes Research Group, Inc.
state: Michigan
city: Fort Gratiot
country: United States
facility: Hamzavi Dermatology
state: Michigan
city: Saint Louis
country: United States
facility: Central Dermatology PC
state: Missouri
city: Omaha
country: United States
facility: Skin Specialists, P.C
state: Nebraska
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Stony Brook
country: United States
facility: DermResearchCenter of New York, Inc
state: New York
city: Bexley
country: United States
facility: Bexley Dermatology Research
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Fairborn
country: United States
facility: Wright State Univ School of Medicine
state: Ohio
city: Mason
country: United States
facility: Dermatologists of Southwest Ohio, Inc.
state: Ohio
city: Portland
country: United States
facility: Oregon Dermatology and Research Center
state: Oregon
city: Portland
country: United States
facility: OHSU Center for Health and Healing
state: Oregon
city: Exton
country: United States
facility: Dermatology and Skin Surgery Center
state: Pennsylvania
city: Johnston
country: United States
facility: Clinical Partners LLC
state: Rhode Island
city: Charleston
country: United States
facility: Dermatology & Laser Center of Charleston
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Bellaire
country: United States
facility: Bellaire Dermatology
state: Texas
city: Dallas
country: United States
facility: Modern Research Associates PLLC
state: Texas
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research, Inc.
state: Texas
city: San Antonio
country: United States
facility: Texas Dermatology and Laser Specialists
state: Texas
city: Sugar Land
country: United States
facility: Acclaim Dermatology, PLLC
state: Texas
city: Murray
country: United States
facility: University of Utah MidValley Dematology
state: Utah
city: Norfolk
country: United States
facility: Virginia Clinical Research
state: Virginia
city: Tacoma
country: United States
facility: Multicare Health System
state: Washington
city: Calgary
country: Canada
facility: Kirk Barber Research
state: Alberta
city: Calgary
country: Canada
facility: Institute for Skin Advancement
state: Alberta
city: Edmonton
country: Canada
facility: Stratica Medical
state: Alberta
city: Surrey
country: Canada
facility: Dr. Chih-ho Hong Medical Inc.
state: British Columbia
city: Surrey
country: Canada
facility: Enverus Medical Research
state: British Columbia
city: Barrie
country: Canada
facility: Simcoderm Medical & Surgical Dermatology Centre
state: Ontario
city: Etobicoke
country: Canada
facility: Kingsway Clinical Research
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc
state: Ontario
city: Niagara Falls
country: Canada
facility: Allergy Research Canada Inc.
state: Ontario
city: Peterborough
country: Canada
facility: SKiN Centre for Dermatology
state: Ontario
city: Richmond Hill
country: Canada
facility: The Centre for Dermatology
state: Ontario
city: Sudbury
country: Canada
facility: Medicor Research Inc
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research Inc
state: Ontario
city: Windsor
country: Canada
facility: XLR8 Medical Research
state: Ontario
city: Montreal
country: Canada
facility: Innovaderm Research Inc
state: Quebec
city: Quebec
country: Canada
facility: Centre de Recherche Dermatologique de Quebec Metropolitain
city: Richmond Hill
country: Canada
facility: York Dermatology Center
city: Caguas
country: Puerto Rico
facility: Office of Dr. Samuel Sanchez PSC
city: Carolina
country: Puerto Rico
facility: Office of Dr. Alma M. Cruz
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine CAIMED Center
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC
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: Simpson EL, Bissonnette R, Paller AS, King B, Silverberg JI, Reich K, Thyssen JP, Doll H, Sun L, DeLozier AM, Nunes FP, Eichenfield LF. The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): a clinical outcome measure for the severity of atopic dermatitis. Br J Dermatol. 2022 Oct;187(4):531-538. doi: 10.1111/bjd.21615. Epub 2022 Aug 21.
citation: Rosmarin D, Casillas M, Chen S, Dawson Z, Pierce E, Zhang H, Bukhalo M, Smith S. Onset of Symptom Relief Reported in Daily Diaries of Patients With Atopic Dermatitis Treated With Baricitinib in a United States Clinical Trial (BREEZE-AD5). J Cutan Med Surg. 2022 May-Jun;26(3):262-266. doi: 10.1177/12034754211073661. Epub 2022 Jan 28.
citation: Silverberg JI, Boguniewicz M, Waibel J, Weisman J, Strowd L, Sun L, Ding Y, Feely M, Nunes FP, Simpson EL. Clinical Tailoring of Baricitinib 2 mg in Atopic Dermatitis: Baseline Body Surface Area and Rapid Onset of Action Identifies Response at Week 16. Dermatol Ther (Heidelb). 2022 Jan;12(1):137-148. doi: 10.1007/s13555-021-00640-7. Epub 2021 Nov 30.
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: 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.