A Multi-omics Disease Signature Trial in Adult Patients With Moderate to Severe AD

Study Overview
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Brief Summary
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This clinical trial will investigate the effectiveness and safety of a new active ingredient (LEO 138559) in the treatment of moderate to severe atopic dermatitis (AD). It is given by subcutaneous injection. Some people in the trial will instead receive Dupixent® which is an approved treatment for moderate to severe AD. Dupixent® is also given by subcutaneous injection. The main aim of this clinical trial is to investigate which changes in biomarkers in the skin are caused by LEO 138559 and Dupixent®. The trial includes a screening phase of up to 4 weeks, followed by a treatment period of 16 weeks, and a safety follow-up period of 16 weeks.

Official Title
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A Randomized, Double-blinded, Active Comparator-controlled, 16-week, Single-site, Exploratory, Mechanistic Trial to Assess the Effect of LEO 138559 on the Molecular Signature and Safety in Adults With Moderate to Severe Atopic Dermatitis.

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: LEO 138559
* Drug: Dupixent®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of AD [as defined by the American Academy of Dermatology (AAD) Consensus Criteria] that has been present for ≥1 year prior to screening. Subjects who have a recent history (within 6 months before screening) of inadequate response to treatment with topical medication, or for whom topical treatments are otherwise medically inadvisable. EASI score ≥12 at screening and ≥16 at baseline. vIGA-AD score ≥3 at screening and baseline. Body surface area (BSA) of AD involvement ≥10% at screening and baseline. Worst Daily Pruritus NRS (weekly average) of ≥3 points at baseline. Exclusion Criteria: Treatment with systemic immunosuppressive/immunomodulating medication (excluding systemic antihistamines if taken at stable dose already before baseline), e.g., JAK inhibitors, immunoglobulin/blood products, or phototherapy within 4 weeks or 5 half-lives prior to baseline, whichever is longer. Treatment with systemic corticosteroids within 4 weeks prior to baseline (NOTE: Inhaled or intranasal steroids equivalent to doses including and up to 500 µg beclometasone (or equivalent) daily is allowed). Treatment with biologics within 5 half-lives (if known) or 16 weeks prior to baseline, whichever is longer. Treatment with TCS, TCI, or topical PDE-4 inhibitor within 1 week prior to baseline (NOTE: Patient may be rescreened (one time) if failed for this criterion. Intake of nonsteroidal anti-inflammatory drugs (NSAIDs) within 1 week prior to baseline. Intake of paracetamol will be allowed. Treatment with a live (attenuated) vaccine within 12 weeks prior to baseline. Clinically significant active chronic or acute infection requiring systemic treatment within 4 weeks prior to baseline that may compromise the safety of the subject. Clinically significant abnormalities detected on vital signs or ECG (apart from 1st degree atrioventricular (AV) block that is allowed). Serious heart conditions, chronic lung diseases. Acute asthma, acute bronchospasm, moderate to severe asthma. Skin infection within 1 week prior to the baseline visit. Presence of hepatitis B or C infection at screening. Active inflammatory bowel disease (IBD) or history of IBD, anaphylaxis, immune complex disease, pancreatic disease, zoster infections, viral skin infections (including eczema herpeticum) or known or suspected history of immunosuppressive disorder. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening. Subject has a positive test for tuberculosis at screening. Subject is pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: LEO 138559<br>Participants will receive injections of LEO 138559 from Week 0 (baseline) to Week 16 (end of treatment). | Drug: LEO 138559<br>* LEO 138559 is an antibody given by subcutaneous injection.<br>|
| Active Comparator: Dupixent®<br>Participants will receive injections of Dupixent® from Week 0 (baseline) to Week 16 (end of treatment). | Drug: Dupixent®<br>* Dupixent® is an antibody given by subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gene expression typically associated with atopic dermatitis in lesional skin biopsies from baseline to week 4 | Lesional skin biopsies will be evaluated by single cell RNA sequencing to evaluate global gene expression | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent adverse events from baseline to week 16 per subject |  | Between baseline and week 16 |