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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 (BREEZE-AD4)

Primary Purpose

Atopic Dermatitis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Baricitinib
Placebo
Topical corticosteroid
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atopic Dermatitis focused on measuring eczema, atopic eczema

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, 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 and/or 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.

Sites / Locations

  • Universitätsklinikum Graz
  • Universitätsklinik Innsbruck
  • KA Rudolfstiftung
  • AKH
  • Sozialmed. Zentrum Ost - Donauspital
  • Cliniques Universitaires Saint-Luc
  • Universitair Ziekenhuis Brussel
  • Universitair Ziekenhuis Gent
  • UZ Leuven - Campus Sint-Rafaël
  • Cedoes Centro Diagnostico Pequisa Osteoporose E Santo Ltd
  • Irmandade da Santa Casa de Misericordia de Porto Alegre
  • Hospital Moinhos de Vento - Instituto de Educação e Pesquisa
  • CCBR Brasil Centro de Analises e Pesquisas Clínicas LTDA
  • IDERJ - Instituto de Dermatologia e Estética do Brasil
  • Faculdade de Ciências Médicas - UNICAMP
  • Fundação Faculdade de Medicina do ABC
  • Hospital das Clinicas da FMRP
  • Hospital da Clinicas da Faculdade de Medicina da USP
  • Terveystalo Tampere
  • Helsinki University Central Hospital
  • Hospital Mehiläinen Neo
  • Hôpital de Pontchaillou
  • CHU de Besancon Hopital Jean Minjoz
  • CHU de Bordeaux Hopital Saint Andre
  • Hôpital C. HURIEZ
  • Hôpital Emile Muller
  • Chru De Nantes Hotel-Dieu
  • CHU de Nice Hopital de L'Archet
  • Hopital Sainte Anne (H.I.A)
  • Hopital Larrey
  • Centre Hospitalier de Valence
  • Universitätsklinikum Heidelberg
  • Hautarztpraxis Dr. Leitz und Kollegen
  • Universitätsklinikum Erlangen
  • Klinikum Rechts der Isar der TU München
  • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
  • Elbe Kliniken Stade Buxtehude GmbH Klinikum Buxtehude
  • Medizinische Hochschule Hannover
  • Klinische Forschung Osnabrück
  • Fachklinik Bad Bentheim
  • St Josef-Hospital Bochum
  • Universitätsklinikum Bonn
  • Universitaetsklinikum Essen
  • Universitätsklinikum Münster
  • Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
  • Universitätsklinikum Jena
  • Charité Universitätsmedizin Berlin
  • Universitätsklinikum Hamburg - Eppendorf
  • Fondazione IRCCS Osp.Maggiore Policlinico - Dermatologia
  • Ospedale Clinicizzato San Donato
  • Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
  • Azienda Ospedaliera Umberto I
  • Spedali Civili - Universita degli Studi
  • Fondazione Universitaria degli Studi G D'Annunzio
  • Azienda Ospedaliera di Perugia
  • Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia
  • Policlinico di Tor Vergata
  • Ospedale Policlinico Giambattista Rossi, Borgo Roma
  • Yanagihara dermatology clinic
  • Fumimori Clinic
  • Queen's Square Dermatology and Allergology
  • Noguchi Dermatology
  • Yoshioka Dermatology Clinic
  • Kume Clinic
  • Sanrui Dermatology Clinic
  • Iidabashi Clinic
  • Nihonbashi Sakura Clinic
  • Sumire Dermatology Clinic
  • Tachikawa Dermatology Clinic
  • Academisch Medisch Centrum
  • Bravis Ziekenhuis
  • Amphia Ziekenhuis
  • NZOZ Specjalistyczna Przychodnia Dermatologiczna Specderm
  • Centrum Badan Klinicznych, PI House
  • Centrum Medyczne Angelius Provita
  • Barbara Rewerska DIAMOND CLINIC
  • Dermed Centrum Medyczne Sp. z o.o.
  • Miejski Szpital Zespolony w Olsztynie Klinika Dermatologii
  • DermoDent, Centrum Medyczne Czajkowscy
  • LASER CLINIC Specjalistyczne Gabinety Lekarskie
  • Wojskowy Instytut Medyczny CSK MON
  • Centralny Szpital Kliniczny MSW Klinika Dermatologii
  • State scientific centre for dermatovenerology and cosmetolog
  • First Moscow State Medical University n.a. Sechenov
  • LLC ArsVitae NorthWest
  • LLC Medical Center "Kurator"
  • SPb SBHI Skin-venerologic dispensary #10
  • Hospital Universitari de Bellvitge
  • Hospital Univ. Puerta de Hierro
  • Hospital Universitario Quiron Madrid
  • Hospital Universitario de Torrejon
  • Hospital de Manises
  • Hospital De Basurto
  • Hospital Universitario Dr Pesset
  • Kantonsspital St. Gallen
  • Inselspital Bern
  • Universitätsspital Zürich
  • Salford Royal NHS Foundation Trust
  • West Glasgow Ambulatory Care Hospital
  • Whipps Cross University Hospital
  • Broadgreen Hospital
  • Guys/St. Thomas Hospital
  • The Dudley Group NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

4 mg Baricitinib

2 mg Baricitinib

1 mg Baricitinib

Placebo

Arm Description

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Placebo administered orally once daily in combination with topical corticosteroids.

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.

Secondary Outcome Measures

Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who permanently discontinue, are rescued, or are without at least 1 post-baseline observation.
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Percentage of Participants Achieving EASI90
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.
Percent Change From Baseline in EASI Score
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). Least Squares Mean (LSM) were calculated using mixed model repeated measures (MMRM) model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline score and baseline score-by-visit-interaction as fixed continuous effects.
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.
Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)
The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.
Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)
The ADSS is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep due to itch, frequency of waking due to itch, and difficulty getting back to sleep last night due to itch. Item 2 frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep "last night." Each item is scored individually. LS Mean were calculated using an MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in Skin Pain NRS
Skin Pain NRS is a participant-administered,11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LS Mean were calculated using MMRM model includes treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Percentage of Participants Achieving IGA of 0 or 1 With a >=2-point Improvement
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Percentage of Participants Achieving EASI50
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI50 is defined as a ≥ 50% improvement from baseline in the EASI score.
Percentage of Participants Achieving EASI75
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Percentage of Participants Achieving IGA of 0
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Change From Baseline in SCORAD
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Percentage of Participants Achieving SCORAD90
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the SCORAD score.
Change From Baseline in Body Surface Area (BSA) Affected
The BSA affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1*BSAhead and neck + 0.3*BSAtrunk + 0.2* BSAupper limbs + 0.4*BSAlower limbs. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline-by-visit-interaction as fixed continuous effects.
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment
Percentage of participants developing skin infections requiring antibiotic treatment.
Mean Number of Days Without Topical Corticosteroids (TCS) Use
The ANCOVA model includes treatment, region, and baseline disease severity (IGA) as factors.
Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)
Average weights of full tubes were used to determine the dispensed weights for each region. Returned tubes were weighed with cap without carton to determine the amount of TCS in grams (g) used at each visit. Analysis was done via analysis of variance (ANOVA), with geographic region, baseline disease severity, and treatment as factors in the model.
Percent Change From Baseline in Itch NRS
The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.
Percent Change From Baseline in Itch NRS at Week 24
The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.
Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)
The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by visit-interactions as fixed continuous effects.
Change From Baseline in the Patient Global Impression of Severity - Atopic Dermatitis (PGI-S-AD) Score
The PGI-S-AD is a single-item question asking the participant how they would rate their overall AD symptoms over the past 24 hours, using a daily diary. The 5 categories of responses are "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe." LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline on the Hospital Anxiety Depression Scale (HADS)
The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in the Dermatology Life Quality Index (DLQI)
The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a little," "a lot," and "very much," with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or "not relevant" responses scored as "0." Scores range from 0 to 30 ("no impact on participant's life" to "extremely large effect on participant's life"), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire
The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm
The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)
EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.

Full Information

First Posted
February 5, 2018
Last Updated
May 20, 2023
Sponsor
Eli Lilly and Company
Collaborators
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT03428100
Brief Title
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
Acronym
BREEZE-AD4
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

2. Study Status

Record Verification Date
May 15, 2023
Overall Recruitment Status
Completed
Study Start Date
May 15, 2018 (Actual)
Primary Completion Date
November 25, 2019 (Actual)
Study Completion Date
April 20, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
Collaborators
Incyte Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
Keywords
eczema, atopic eczema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
463 (Actual)

8. Arms, Groups, and Interventions

Arm Title
4 mg Baricitinib
Arm Type
Experimental
Arm Description
4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Arm Title
2 mg Baricitinib
Arm Type
Experimental
Arm Description
2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Arm Title
1 mg Baricitinib
Arm Type
Experimental
Arm Description
1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered orally once daily in combination with topical corticosteroids.
Intervention Type
Drug
Intervention Name(s)
Baricitinib
Other Intervention Name(s)
LY3009104
Intervention Description
Administered orally.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered orally.
Intervention Type
Drug
Intervention Name(s)
Topical corticosteroid
Intervention Description
Administered as standard-of-care.
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)
Description
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Time Frame
Week 16
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)
Description
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who permanently discontinue, are rescued, or are without at least 1 post-baseline observation.
Time Frame
Week 16
Title
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement
Description
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time Frame
Week 16
Title
Percentage of Participants Achieving EASI90
Description
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.
Time Frame
Week 16
Title
Percent Change From Baseline in EASI Score
Description
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). Least Squares Mean (LSM) were calculated using mixed model repeated measures (MMRM) model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline score and baseline score-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)
Description
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.
Time Frame
Week 16
Title
Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)
Description
The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.
Time Frame
Week 16
Title
Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)
Description
The ADSS is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep due to itch, frequency of waking due to itch, and difficulty getting back to sleep last night due to itch. Item 2 frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep "last night." Each item is scored individually. LS Mean were calculated using an MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Change From Baseline in Skin Pain NRS
Description
Skin Pain NRS is a participant-administered,11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LS Mean were calculated using MMRM model includes treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Percentage of Participants Achieving IGA of 0 or 1 With a >=2-point Improvement
Description
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time Frame
Week 24
Title
Percentage of Participants Achieving EASI50
Description
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI50 is defined as a ≥ 50% improvement from baseline in the EASI score.
Time Frame
Week 16
Title
Percentage of Participants Achieving EASI75
Description
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Time Frame
Week 24
Title
Percentage of Participants Achieving IGA of 0
Description
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time Frame
Week 16
Title
Change From Baseline in SCORAD
Description
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Percentage of Participants Achieving SCORAD90
Description
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the SCORAD score.
Time Frame
Week 16
Title
Change From Baseline in Body Surface Area (BSA) Affected
Description
The BSA affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1*BSAhead and neck + 0.3*BSAtrunk + 0.2* BSAupper limbs + 0.4*BSAlower limbs. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment
Description
Percentage of participants developing skin infections requiring antibiotic treatment.
Time Frame
Week 16
Title
Mean Number of Days Without Topical Corticosteroids (TCS) Use
Description
The ANCOVA model includes treatment, region, and baseline disease severity (IGA) as factors.
Time Frame
Week 16
Title
Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)
Description
Average weights of full tubes were used to determine the dispensed weights for each region. Returned tubes were weighed with cap without carton to determine the amount of TCS in grams (g) used at each visit. Analysis was done via analysis of variance (ANOVA), with geographic region, baseline disease severity, and treatment as factors in the model.
Time Frame
Week 16
Title
Percent Change From Baseline in Itch NRS
Description
The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Percent Change From Baseline in Itch NRS at Week 24
Description
The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.
Time Frame
Baseline, Week 24
Title
Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)
Description
The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by visit-interactions as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Change From Baseline in the Patient Global Impression of Severity - Atopic Dermatitis (PGI-S-AD) Score
Description
The PGI-S-AD is a single-item question asking the participant how they would rate their overall AD symptoms over the past 24 hours, using a daily diary. The 5 categories of responses are "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe." LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Change From Baseline on the Hospital Anxiety Depression Scale (HADS)
Description
The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Change From Baseline in the Dermatology Life Quality Index (DLQI)
Description
The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a little," "a lot," and "very much," with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or "not relevant" responses scored as "0." Scores range from 0 to 30 ("no impact on participant's life" to "extremely large effect on participant's life"), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire
Description
The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Change From Baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm
Description
The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16
Title
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)
Description
EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time Frame
Baseline, Week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, 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 and/or 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Universitätsklinikum Graz
City
Graz
State/Province
Steiermark
ZIP/Postal Code
8036
Country
Austria
Facility Name
Universitätsklinik Innsbruck
City
Innsbruck
State/Province
Tyrol
ZIP/Postal Code
6020
Country
Austria
Facility Name
KA Rudolfstiftung
City
Wien
ZIP/Postal Code
1030
Country
Austria
Facility Name
AKH
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Sozialmed. Zentrum Ost - Donauspital
City
Wien
ZIP/Postal Code
1220
Country
Austria
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Universitair Ziekenhuis Brussel
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven - Campus Sint-Rafaël
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Cedoes Centro Diagnostico Pequisa Osteoporose E Santo Ltd
City
Vitoria
State/Province
ES
ZIP/Postal Code
29055 450
Country
Brazil
Facility Name
Irmandade da Santa Casa de Misericordia de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90020-090
Country
Brazil
Facility Name
Hospital Moinhos de Vento - Instituto de Educação e Pesquisa
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90560-030
Country
Brazil
Facility Name
CCBR Brasil Centro de Analises e Pesquisas Clínicas LTDA
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
22271-100
Country
Brazil
Facility Name
IDERJ - Instituto de Dermatologia e Estética do Brasil
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
22470-220
Country
Brazil
Facility Name
Faculdade de Ciências Médicas - UNICAMP
City
Campinas
State/Province
Sao Paulo
ZIP/Postal Code
13083-887
Country
Brazil
Facility Name
Fundação Faculdade de Medicina do ABC
City
Santo André
State/Province
Sao Paulo
ZIP/Postal Code
09060-650
Country
Brazil
Facility Name
Hospital das Clinicas da FMRP
City
Ribeirao Preto
State/Province
SP
ZIP/Postal Code
14048-900
Country
Brazil
Facility Name
Hospital da Clinicas da Faculdade de Medicina da USP
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
Terveystalo Tampere
City
Tampere
State/Province
Irkanmaa
ZIP/Postal Code
33100
Country
Finland
Facility Name
Helsinki University Central Hospital
City
Helsinki
ZIP/Postal Code
00250
Country
Finland
Facility Name
Hospital Mehiläinen Neo
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Hôpital de Pontchaillou
City
Rennes
State/Province
Cedex 9
ZIP/Postal Code
35033
Country
France
Facility Name
CHU de Besancon Hopital Jean Minjoz
City
Besancon Cedex
ZIP/Postal Code
25030
Country
France
Facility Name
CHU de Bordeaux Hopital Saint Andre
City
Bordeaux Cedex
ZIP/Postal Code
33075
Country
France
Facility Name
Hôpital C. HURIEZ
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital Emile Muller
City
Mulhouse
ZIP/Postal Code
68100
Country
France
Facility Name
Chru De Nantes Hotel-Dieu
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
CHU de Nice Hopital de L'Archet
City
Nice cedex 3
ZIP/Postal Code
06202
Country
France
Facility Name
Hopital Sainte Anne (H.I.A)
City
Toulon Cedex 9
ZIP/Postal Code
83800
Country
France
Facility Name
Hopital Larrey
City
Toulouse cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Centre Hospitalier de Valence
City
Valence
ZIP/Postal Code
26953
Country
France
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Hautarztpraxis Dr. Leitz und Kollegen
City
Stuttgart
State/Province
Baden-Württemberg
ZIP/Postal Code
70178
Country
Germany
Facility Name
Universitätsklinikum Erlangen
City
Erlangen
State/Province
Bayern
ZIP/Postal Code
91054
Country
Germany
Facility Name
Klinikum Rechts der Isar der TU München
City
München
State/Province
Bayern
ZIP/Postal Code
80802
Country
Germany
Facility Name
Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
City
Frankfurt am Main
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Facility Name
Elbe Kliniken Stade Buxtehude GmbH Klinikum Buxtehude
City
Buxtehude
State/Province
Niedersachsen
ZIP/Postal Code
21614
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30449
Country
Germany
Facility Name
Klinische Forschung Osnabrück
City
Osnabrück
State/Province
Niedersachsen
ZIP/Postal Code
49074
Country
Germany
Facility Name
Fachklinik Bad Bentheim
City
Bad Bentheim
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48455
Country
Germany
Facility Name
St Josef-Hospital Bochum
City
Bochum
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
44791
Country
Germany
Facility Name
Universitätsklinikum Bonn
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitaetsklinikum Essen
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitätsklinikum Münster
City
Münster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48149
Country
Germany
Facility Name
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Universitätsklinikum Jena
City
Jena
State/Province
Thüringen
ZIP/Postal Code
07743
Country
Germany
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum Hamburg - Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Fondazione IRCCS Osp.Maggiore Policlinico - Dermatologia
City
Milano
State/Province
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
Ospedale Clinicizzato San Donato
City
San Donato Milanese
State/Province
Milan
ZIP/Postal Code
20097
Country
Italy
Facility Name
Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
City
Roma
State/Province
Rome
ZIP/Postal Code
00161
Country
Italy
Facility Name
Azienda Ospedaliera Umberto I
City
Ancona
ZIP/Postal Code
60020
Country
Italy
Facility Name
Spedali Civili - Universita degli Studi
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Fondazione Universitaria degli Studi G D'Annunzio
City
Chieti
ZIP/Postal Code
66100
Country
Italy
Facility Name
Azienda Ospedaliera di Perugia
City
Perugia
ZIP/Postal Code
06129
Country
Italy
Facility Name
Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia
City
Reggio Emilia
ZIP/Postal Code
42123
Country
Italy
Facility Name
Policlinico di Tor Vergata
City
Roma
ZIP/Postal Code
00133
Country
Italy
Facility Name
Ospedale Policlinico Giambattista Rossi, Borgo Roma
City
Verona
ZIP/Postal Code
37134
Country
Italy
Facility Name
Yanagihara dermatology clinic
City
Ainokawa, Ichikawa-shi
State/Province
Chiba
ZIP/Postal Code
272-0143
Country
Japan
Facility Name
Fumimori Clinic
City
Fukuoka-shi
State/Province
Fukuoka
ZIP/Postal Code
815-0082
Country
Japan
Facility Name
Queen's Square Dermatology and Allergology
City
Nishi-ku, Yokohama-city
State/Province
Kanagawa
ZIP/Postal Code
220-6208
Country
Japan
Facility Name
Noguchi Dermatology
City
Kashima-machi, Kamimashiki-gun
State/Province
Kumamoto
ZIP/Postal Code
861-3101
Country
Japan
Facility Name
Yoshioka Dermatology Clinic
City
Neyagawa-shi
State/Province
Osaka
ZIP/Postal Code
572-0838
Country
Japan
Facility Name
Kume Clinic
City
Nishi-ku Sakai-shi
State/Province
Osaka
ZIP/Postal Code
593-8324
Country
Japan
Facility Name
Sanrui Dermatology Clinic
City
Ohmiya-ku,Saitama-shi
State/Province
Saitama
ZIP/Postal Code
330-0854
Country
Japan
Facility Name
Iidabashi Clinic
City
Chiyoda-ku
State/Province
Tokyo
ZIP/Postal Code
102-0072
Country
Japan
Facility Name
Nihonbashi Sakura Clinic
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
103-0025
Country
Japan
Facility Name
Sumire Dermatology Clinic
City
Edogawa-ku
State/Province
Tokyo
ZIP/Postal Code
133-0057
Country
Japan
Facility Name
Tachikawa Dermatology Clinic
City
Tachikawa-shi
State/Province
Tokyo
ZIP/Postal Code
190-0023
Country
Japan
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Bravis Ziekenhuis
City
Bergen op Zoom
ZIP/Postal Code
4624 VT
Country
Netherlands
Facility Name
Amphia Ziekenhuis
City
Breda
ZIP/Postal Code
4818 CK
Country
Netherlands
Facility Name
NZOZ Specjalistyczna Przychodnia Dermatologiczna Specderm
City
Bialystok
ZIP/Postal Code
15-375
Country
Poland
Facility Name
Centrum Badan Klinicznych, PI House
City
Gdansk
ZIP/Postal Code
80-546
Country
Poland
Facility Name
Centrum Medyczne Angelius Provita
City
Katowice
ZIP/Postal Code
40-611
Country
Poland
Facility Name
Barbara Rewerska DIAMOND CLINIC
City
Krakow
ZIP/Postal Code
31-559
Country
Poland
Facility Name
Dermed Centrum Medyczne Sp. z o.o.
City
Lodz
ZIP/Postal Code
90-265
Country
Poland
Facility Name
Miejski Szpital Zespolony w Olsztynie Klinika Dermatologii
City
Olsztyn
ZIP/Postal Code
10-229
Country
Poland
Facility Name
DermoDent, Centrum Medyczne Czajkowscy
City
Osielsko
ZIP/Postal Code
86-031
Country
Poland
Facility Name
LASER CLINIC Specjalistyczne Gabinety Lekarskie
City
Szczecin
ZIP/Postal Code
70-332
Country
Poland
Facility Name
Wojskowy Instytut Medyczny CSK MON
City
Warsaw
ZIP/Postal Code
04-141
Country
Poland
Facility Name
Centralny Szpital Kliniczny MSW Klinika Dermatologii
City
Warszawa
ZIP/Postal Code
02-507
Country
Poland
Facility Name
State scientific centre for dermatovenerology and cosmetolog
City
Moscow
ZIP/Postal Code
107076
Country
Russian Federation
Facility Name
First Moscow State Medical University n.a. Sechenov
City
Moscow
ZIP/Postal Code
119991
Country
Russian Federation
Facility Name
LLC ArsVitae NorthWest
City
Saint-Petersburg
ZIP/Postal Code
194223
Country
Russian Federation
Facility Name
LLC Medical Center "Kurator"
City
Saint-Petersburg
ZIP/Postal Code
196240
Country
Russian Federation
Facility Name
SPb SBHI Skin-venerologic dispensary #10
City
St. Petersburg
ZIP/Postal Code
194021
Country
Russian Federation
Facility Name
Hospital Universitari de Bellvitge
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Univ. Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28220
Country
Spain
Facility Name
Hospital Universitario Quiron Madrid
City
Pozuelo de Alarcon
State/Province
Madrid
ZIP/Postal Code
28223
Country
Spain
Facility Name
Hospital Universitario de Torrejon
City
Torrejón de Ardoz
State/Province
Madrid
ZIP/Postal Code
28850
Country
Spain
Facility Name
Hospital de Manises
City
Manises
State/Province
Valencia
ZIP/Postal Code
46940
Country
Spain
Facility Name
Hospital De Basurto
City
Bilbao
State/Province
Vizcaya
ZIP/Postal Code
48013
Country
Spain
Facility Name
Hospital Universitario Dr Pesset
City
Valencia
ZIP/Postal Code
46017
Country
Spain
Facility Name
Kantonsspital St. Gallen
City
St. Gallen
State/Province
Sankt Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Inselspital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Universitätsspital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
State/Province
Greater Manchester
ZIP/Postal Code
M6 8HD
Country
United Kingdom
Facility Name
West Glasgow Ambulatory Care Hospital
City
Glasgow
State/Province
Lanarkshire
ZIP/Postal Code
G3 8SJ
Country
United Kingdom
Facility Name
Whipps Cross University Hospital
City
Leytonstone
State/Province
London
ZIP/Postal Code
E11 1NR
Country
United Kingdom
Facility Name
Broadgreen Hospital
City
Liverpool
State/Province
Merseyside
ZIP/Postal Code
L14 3LB
Country
United Kingdom
Facility Name
Guys/St. Thomas Hospital
City
London
State/Province
Surrey
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
The Dudley Group NHS Foundation Trust
City
Dudley
State/Province
West Midlands
ZIP/Postal Code
DY1 2HQ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
http://vivli.org/
Citations:
PubMed Identifier
36255569
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.
Results Reference
derived
PubMed Identifier
33826132
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.
Results Reference
derived
Links:
URL
https://www.lillytrialguide.com/en-US/studies/eczema/JAIN#?postal=
Description
A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis (Eczema) Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Adv

Learn more about this trial

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

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