E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Atopic dermatitis also known as Eczema |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To test the hypothesis that baricitinib 4 mg + topical corticosteroids (TCS) or baricitinib 2 mg + TCS is superior to placebo + TCS in the treatment of moderate to severe atopic dermatitis |
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E.2.2 | Secondary objectives of the trial |
• To test the hypothesis that baricitinib 1 mg + topical corticosteroids (TCS) is superior to placebo + TCS in the treatment of patients with moderate to severe atopic dermatitis. • To compare the efficacy of baricitinib 4 mg + TCS, baricitinib 2 mg + TCS, or baricitinib 1 mg + TCS to placebo + TCS in atopic dermatitis during the double blind placebo controlled treatment period as measured by improvement of signs and symptoms of atopic dermatitis. • To compare the efficacy of baricitinib 4 mg + TCS, baricitinib 2 mg + TCS, or baricitinib 1 mg + TCS to placebo + TCS in atopic dermatitis during the double blind placebo controlled treatment period as assessed by patient reported outcome measures.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Randomized DownTitration Substudy at week 52 During the long term extension (Period 3), eligible patients will participate in a downtitration substudy. The objective of the substudy is to evaluate the possibility of maintaining efficacy with a lower dose of baricitinib in patients with response (IGA 0 or 1) or partial response (IGA 2) to baricitinib 2-mg QD or 4-mg QD in combination with topical corticosteroids.
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E.3 | Principal inclusion criteria |
• Have been diagnosed with moderate to severe Atopic Eczema (Atopic Dermatitis) for at least 12 months. • Have had inadequate response or intolerance to existing topical (applied to the skin) medications within 6 months preceding screening. • Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period and throughout the study). • Agree to use emollients daily. • Have a medical contraindication to cyclosporine A, or had intolerance and/or unacceptable toxicity or inadequate response to cyclosporine A in the past.
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E.4 | Principal 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. - Received any parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study. - Have had an intra-articular corticosteroid injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization. • Have high blood pressure characterized by a repeated systolic blood pressure >160 millimeters of mercury (mm Hg) or diastolic blood pressure >100 mm Hg. • Have had major surgery within the past eight weeks or are planning major surgery during the study. • Have experienced any of the following within 12 weeks of screening: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure. • Have a history of recurrent (≥ 2) VTE or are considered at high risk of VTE as deemed by the investigator. • Have a history or presence of cardiovascular, respiratory, hepatic, chronic liver disease gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness. • Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection including herpes zoster, tuberculosis. • Have specific laboratory abnormalities. • Have received certain treatments that are contraindicated. • Pregnant or breastfeeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving Investigator’s Global Assessment (IGA) of 0 or 1 with a ≥ 2 point improvement
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1, • Proportion of patients achieving Investigator’s Global Assessment (IGA) of 0 or 1 with a ≥ 2 point improvement • Proportion of patients achieving EASI75 • Proportion of patients achieving EASI 90 • Mean change from baseline in EASI score • Proportion of patients achieving SCORAD75 • Mean change from baseline in Skin Pain NRS
2; • Proportion of patients achieving a 4-point improvement in Itch NRS 3; • Mean change from baseline in the score of Item 2 of the ADSS 4; • Proportion of patients achieving IGA of 0 or 1 with a ≥2-point improvement from baseline • Proportion of patients achieving EASI75
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1; assessed at week 16 2; assessed at 16, 4, 2, and 1 weeks 3; assessed at 16 weeks and 1 week. 4; assessed at 24 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
96 additional weeks bridging extension |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Brazil |
Finland |
France |
Germany |
Italy |
Japan |
Netherlands |
Poland |
Russian Federation |
Spain |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of the study is the date of the last visit or last scheduled procedure shown in the Schedule of Activities for the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 29 |