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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This open-label study will evaluate the long-term efficacy and safety of baricitinib in adult participants with moderate to severe atopic dermatitis (AD).

Official Title
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A Multicenter, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients With Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Baricitinib


Participation Criteria
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Eligibility Criteria
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Have participated in Study JAIW (NCT03435081), and meet specific completion requirements for that study, and do not meet any of the following Exclusions: Have significant uncontrolled cerebro-cardiovascular (e.g., myocardial infarction [MI], unstable angina, unstable arterial hypertension, severe heart failure, or cerebrovascular accident), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neuropsychiatric disorders, or abnormal laboratory values that developed during a previous baricitinib study that, in the opinion of the investigator, pose an unacceptable risk to the participant if investigational product continues to be administered. Have a known hypersensitivity to baricitinib or any component of this investigational product. Had investigational product permanently discontinued at any time during a previous baricitinib study, except for participants who had investigational product discontinued during originating study because of rescue with an oral systemic AD therapy (e.g., corticosteroid, cyclosporine, methotrexate). Had temporary investigational product interruption continue at the final study visit of a previous baricitinib study and, in the opinion of the investigator, this poses an unacceptable risk for the participant's participation in the study. Pregnant or breastfeeding OR • Have not participated in a Study JAIW (NCT03435081) and satisfy the following 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%- 50% 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) 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 episodes 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, 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.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo/Baricitinib 2-milligram (mg)<br>Open-label 2 mg baricitinib administered orally once daily (QD) to participants who randomized to placebo in the originating study (JAIW). | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|
| Experimental: Baricitinib 1-mg/Baricitinib 2-mg<br>Open-label 2 mg baricitinib administered orally QD to participants who randomized to 1 mg baricitinib in the originating study (JAIW). | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|
| Experimental: Baricitinib 2-mg/Baricitinib 2-mg<br>Open-label 2 mg baricitinib administered orally QD to participants who randomized to 2 mg baricitinib in the originating study (JAIW). | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|
| Experimental: Baricitinib 2-mg Open-Label Addendum<br>Participants were directly enrolled to receive open-label 2 mg baricitinib orally QD. | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Eczema Area and Severity Index 75 (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 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. The results were analyzed using non-responder imputation (NRI). All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as EASI75. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 | The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1. | Week 16 | 
| Percentage of Participants Achieving a Body Surface Area (BSA) of ≤3% | The BSA affected by AD will be assessed for 4 separate body regions: 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. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region * % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD. | Week 16 | 
| Percentage of Participants Achieving a ≥4-Point Improvement in Itch Numeric Rating Scale (NRS) | The 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. | Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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eczema, atopic eczema