A Study of Baricitinib (LY3009104) in Participants With Moderate-to-Severe Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of Baricitinib in eczema.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of Baricitinib in Patients With Moderate-to-Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Baricitinib
* Drug: Placebo
* Drug: Triamcinolone (Optional)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have moderate-to-severe Atopic Dermatitis (AD), as determined by all of the following: EASI of 12 or more Greater than or equal to 10% of body surface area involvement Diagnosed with AD at least 2 years prior Have a history of inadequate clinical response to other eczema treatments Exclusion Criteria: Females who are pregnant or nursing Participants who do not agree to use adequate contraception Are currently experiencing or have a history of: Skin conditions such as psoriasis or lupus erythematosus Skin disease that requires frequent hospitalizations or intravenous treatment Compromised immunity Serious illness that could interfere with study participation, or a clinically important deviation in physical examination, vital sign measurements, electrocardiograms, or abnormalities on laboratory tests Currently experiencing or have a history of: Active or latent Tuberculosis or specific immunity disorders and infections Malignancy or lymphoproliferative diseases in the last 5 years (or cervical, basal or squamous skin cancer re-occurrence in the last 3 years) Human Immunodeficiency Virus (HIV) Hepatitis B, Hepatitis C, or chronic liver disease Have received certain types of vaccinations

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baricitinib<br>Administered once daily in multiple oral dose cohorts for 16 weeks (Triamcinolone 0.1% topical also permitted) | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB028050;Drug: Triamcinolone (Optional)<br>* Administered topically<br>|
| Placebo Comparator: Placebo<br>Administered orally once daily, for 16 weeks (Triamcinolone 0.1% topical also permitted) | Drug: Placebo<br>* Administered orally<br>Drug: Triamcinolone (Optional)<br>* Administered topically<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a 50% or Greater Reduction in the Eczema Area and Severity Index (EASI 50) | The EASI 50, defined as ≥ 50% reduction from baseline in EASI score, assesses extent of disease based on dividing the skin into 4 regions (head/neck, trunk, upper limbs, and lower limbs) and measures the following clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3.The EASI confers a maximum score of 72 with 0 = clear; 0.1 -1 = almost clear; 1.1 -7 = mild; 7.1 - 21 = moderate; 21.1 - 50 = severe; 50.1 - 72 = very severe. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the EASI at Week 16 | The Eczema Area and Severity Index (EASI) assesses extent of disease based on dividing the skin into 4 regions (head/neck, trunk, upper limbs, and lower limbs) and measures the following clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3.The EASI confers a maximum score of 72 with 0 = clear; 0.1 -1 = almost clear; 1.1 -7 = mild; 7.1 - 21 = moderate; 21.1 - 50 = severe; 50.1 - 72 = very severe. Change from baseline were analyzed with a Mixed-effect Model Repeated Measure (MMRM) with fixed effects for treatment, visit, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit included as covariates. | Baseline, Week 16 | 
| Percentage Change From Baseline in the EASI at Week 16 | The Eczema Area and Severity Index (EASI) assesses extent of disease based on dividing the skin into 4 regions (head/neck, trunk, upper limbs, and lower limbs) and measures the following clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3.The EASI confers a maximum score of 72 with 0 = clear; 0.1 -1 = almost clear; 1.1 -7 = mild; 7.1 - 21 = moderate; 21.1 - 50 = severe; 50.1 - 72 = very severe. Changes from baseline were analyzed with an MMRM with fixed effects for treatment, visit, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit included as covariates. | Baseline, Week 16 | 
| Change From Baseline in the Scoring Atopic Dermatitis (SCORAD) at Week 16 | The SCORAD index uses the rule of nines to assess disease extent and evaluates five clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation and (5) lichenification. SCORAD also assesses subjective symptoms of pruritus and sleep loss with Visual Analogue Scales (VAS) where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness). These three aspects: extent of disease (A: 0-102), disease severity (B: 0-18) and 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. Changes from baseline were analyzed with an MMRM with fixed effects for treatment, visit, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit included as covariates. | Baseline, Week 16 | 
| Change From Baseline in the Investigator's Global Assessment (IGA) at Week 16 | The IGA consists of a 6-point severity scale to measure characteristics of erythema, infiltration, papulation, oozing and crusting as guidelines for the overall severity assessment. The scale ranges from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease and 5 = very severe disease). | Baseline, Week 16 | 
| Change From Baseline in the Dermatologic Life Quality Index (DLQI) at Week 16 | 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. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. For all questions, if unanswered the question is scored as 0. Totals range from 0 to 30 (less to more impairment). Changes from baseline in DLQI score were analyzed with an MMRM with fixed effects for treatment, time, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit were included as covariates. | Baseline, Week 16 | 
| Change From Baseline in the Itch Numerical Rating Scale (NRS) at Week 16 | 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 circling the number that best describes the worst level of itching in the past 24 hours. Changes from baseline were analyzed with an MMRM with fixed effects for treatment, time, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit were included as covariates. | Baseline, Week 16 | 
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Baricitinib | Pharmacokinetics (PK): Maximum serum concentration (Cmax) of Baricitinib | Week (Wk) 0: Predose, 15-30 minutes (min) postdose; Wk 4: 1.5 - 4 hour (hr) postdose; Wk 8: 4 - 8 hr postdose; Wk 12: Predose; Wk 16: 30 - 90 min postdose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Eczema