Transcriptomic Skin Analysis for Atopic Dermatitis

(LEADS Trial)

Recruiting in Palo Alto (17 mi)

+9 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Dupilumab

Must not be taking: Systemic immunosuppressants, Biologics

Disqualifiers: HIV, Skin diseases, Immunosuppression, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a multi-center, longitudinal study which will characterize the gene expression profiles and transcriptomic endotypes that underlie mild and moderate-severe Atopic dermatitis (AD) and will determine changes in these expression patterns and endotypes in response to standard-of-care treatment. Participants will complete up to ten scheduled study visits with assessment of topical steroid response and dupilumab response (if uncontrolled with topical steroids). Skin samples will be collected at all study visits to determine the gene expression profiles and transcriptomic endotypes that underlie mild vs. moderate-severe AD disease. The investigators will also evaluate the lipidomic, metabolomic, proteomic, and microbiome profiles of AD skin endotypes associated with mild and moderate-severe AD disease. Non-AD participants will serve as a control population. The primary objective of this study is to determine if the type 2-high non-lesional skin (skin tape) endotype is associated with current mild versus moderate-severe AD disease.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications before joining. You must not use systemic immunosuppressive therapies, certain biologics, or specific topical treatments for a specified period before the study starts. Check with the study team to see if your current medications are affected.

What data supports the effectiveness of the drug Dupilumab for treating atopic dermatitis?

Dupilumab has been shown to significantly improve skin inflammation and itching in patients with moderate-to-severe atopic dermatitis by blocking key inflammatory pathways, with studies demonstrating rapid and sustained improvements in clinical outcomes and a favorable safety profile.

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Is the treatment safe for humans?

Dupilumab has shown remarkable effectiveness and safety in treating moderate-to-severe atopic dermatitis, with limited drug-related adverse events. However, there is a small risk of local Staphylococcus aureus infection during treatment.

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What makes the drug Dupilumab unique for treating atopic dermatitis?

Dupilumab is unique because it is the first targeted biological therapy for atopic dermatitis, working by blocking specific proteins (interleukin-4 and interleukin-13) involved in the immune response, which helps improve skin barrier function and reduce inflammation.

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Eligibility Criteria

This trial is for individuals with mild to moderate-severe Atopic Dermatitis (AD). Eligible participants must understand and consent to the study, use FDA-approved birth control if applicable, apply Vanicream moisturizer twice daily, and adhere to asthma medications if they have asthma. Participants should not be pregnant or breastfeeding, have a history of certain cancers or keloids (adults), require systemic immunosuppressants recently, or have used other biologics or phototherapy close to the baseline visit.

Inclusion Criteria

Parent or guardian must be able to understand and complete study-related questionnaires.

I will continue my asthma medication throughout the study.

I agree to use approved birth control methods during the study.

Exclusion Criteria

I only have Atopic Dermatitis and no other skin conditions affecting my skin's outer layer.

You have a history of heavy drinking or drug abuse within the past 2 years.

I have never had keloids form after an injury or surgery.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard-of-care treatment including topical corticosteroids and dupilumab, with skin samples collected at all study visits to determine gene expression profiles.

24 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with final assessments and skin sample collection.

4-8 weeks

Participant Groups

The study aims to analyze gene expression in skin samples from AD patients responding to standard treatments like topical steroids and Dupilumab. It will compare these profiles between mild and severe cases over ten visits. Non-AD participants are controls. The primary goal is seeing if a specific skin endotype correlates with AD severity.

Group I: Experienced Dupilumab atopic dermatitis participants Experimental Treatment 1 Intervention

AD participants already on dupilumab (for \>= 4 months prior to study entry (20 children, 40 adults)) at the start of the study will continue treatment with dupilumab as prescribed by their physician outside of the study. They may also continue treatment with other prescribed topical AD medications outside of the specified target skin area throughout the study; they may continue treatment with other prescribed topical AD medications within the specified target area from Day 7 through Day 140. Long-term dupilumab participants will apply Vanicream™ beginning at Day 0 through Day 7. Long-term dupilumab participants will return for assessment visits at Day 63 and 140. At Day 140, participants will resume application of Vanicream™ through the End of Study Assessment (Day 168).

Group II: Dupilumab-naïve atopic dermatitis participants Experimental Treatment 4 Interventions

On Day 7, dupilumab-naïve AD participants will begin applying topical corticosteroids twice daily to their specified target area, as well as to active lesions on non-target skin. Dupilumab-naïve AD participants will return for a Steroid Assessment Visit at Day 35, when response to topical corticosteroids will be evaluated at the target site by TAA and targeted EASI scoring, and overall management of AD body-wide by topical steroid/moisturizer treatment will be evaluated by EASI score. Participants who are responsive to topical corticosteroids will continue to use them body-wide through Day 140. Participants who are non-responsive to topical corticosteroids at any time before Day 91 will begin use of dupilumab through their penultimate scheduled visit (Day 140-Day 196) and may continue use of topical corticosteroids outside of their specified target area as needed.

Group III: Non-atopic dermatitis participants Active Control 1 Intervention

Approximately 150 will be non-AD controls (including approximately 50 children, 6-17 years of age, and 100 adults, = 18 years of age) Non-AD control participants will apply Vanicream™ beginning at Day 0 through Day 7. Non-AD control participants will return for assessment visits at Day 35, 91, and 140. At Day 140, participants will resume application of Vanicream™ through the End of Study Assessment (Day 168).

Dupilumab is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

🇪🇺 Approved in European Union as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Rochester Medical Center: Department of Dermatology Rochester, NY

Oregon Health & Science University: Department of Dermatology Portland, OR

Icahn School of Medicine at Mount Sinai: Department of Pediatrics Allergy & Immunology New York, NY

University of California, San Diego: Dermatology Clinical Trials Unit La Jolla, CA

More Trial Locations

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID) Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis. [2022] Dupilumab has demonstrated efficacy with acceptable safety in clinical trials in patients with moderate to severe atopic dermatitis (AD).

2. England pubmed.ncbi.nlm.nih.gov

Dupilumab provides rapid and sustained improvement in SCORAD outcomes in adults with moderate-to-severe atopic dermatitis: combined results of four randomized phase 3 trials. [2022] Dupilumab, a first-in-class therapy targeting the two key cytokines involved in the persistent underlying inflammatory pathway in atopic dermatitis (AD), is approved for treatment of moderate-to-severe AD in Europe, USA, Japan and several other countries.

3. United States pubmed.ncbi.nlm.nih.gov

Dupilumab for Atopic Dermatitis-From Clinical Trials to Molecular and Cellular Mechanisms. [2023] Dupilumab is a monoclonal antibody that represents the first approved targeted biological therapy for adults, adolescents, and children older than 6 years with moderate-to-severe atopic dermatitis (AD). Dupilumab binds the shared chain of the interleukin-4 and interleukin-13 receptor blocking the downstream signaling of these cytokines. The clinical improvements induced by dupilumab were associated with remission of the dysregulated immune mechanisms linked with AD. Dupilumab reversed the epidermal barrier defects and improved the global molecular signature of AD. This review seeks to provide an overview on the development of dupilumab as the first target-specific biological treatment for AD, with a description of the clinical trials that have been performed in different age groups, their outcomes, and reported adverse effects. Novel aspects of dupilumab treatment, as well as the current knowledge on the molecular and cellular mechanisms underlying the treatment of AD with dupilumab, are summarized and discussed.

4. England pubmed.ncbi.nlm.nih.gov

Drug evaluation review: dupilumab in atopic dermatitis. [2022] Atopic dermatitis (AD) is characterized by type 2 helper T (Th2) cell-driven inflammation. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways. In Phase I and II studies of adults with moderate-to-severe AD, dupilumab administered as monotherapy or with topical corticosteroids resulted in rapid, significant improvements in clinical efficacy, patient-reported outcomes, and Th2-related serum and tissue biomarkers, and shifted the RNA expression profile of lesional skin to a more nonlesional signature. In all clinical studies to date, dupilumab has shown a favorable safety profile with no dose-limiting toxicity. The robust effects of dupilumab on skin inflammation and pruritus confirm the pathogenic role of IL-4 and IL-13 signaling in adult AD, and further support the application of Th2 cytokine antagonists in the treatment of this disease.

5. Australia pubmed.ncbi.nlm.nih.gov

Association study of transition of laboratory marker levels and transition of disease activity of atopic dermatitis patients treated with dupilumab. [2022] Dupilumab, a fully human monoclonal antibody that blocks signalling pathways of interleukin (IL)-4 and IL-13, is effective in treating patients with atopic dermatitis (AD). We previously showed that transitions of serum thymus and activation-regulated chemokine (TARC) levels and eosinophil numbers were strongly associated with that of AD activity and that the transitions of serum lactate dehydrogenase (LDH) and immunoglobulin E (IgE) levels were weakly and not associated with that of AD activity, respectively, in patients treated without dupilumab.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: Dupilumab leads to an increased chance of head and neck Staphylococcus aureus infection in atopic dermatitis patients. [2023] Dupilumab was the first biological medication licensed to treat atopic dermatitis (AD), and it has shown remarkable effectiveness and safety in the treatment of moderate-to-severe atopic dermatitis. There are limited drug-related adverse events associated with dupilumab in atopic dermatitis (AD) treatment. Here, we present two cases of local Staphylococcus aureus infection during the treatment of atopic dermatitis with dupilumab.

7. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort. [2019] Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials.

8. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): data from a French multicentre retrospective cohort in daily practice. [2022] Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD).

9. United States pubmed.ncbi.nlm.nih.gov

Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-Week results from the Dutch BioDay registry. [2021] Real-life data on long-term effectiveness and safety of dupilumab in atopic dermatitis patients are limited.

10. Netherlands pubmed.ncbi.nlm.nih.gov

Peripheral blood mononuclear cell- transcriptome signatures of atopic dermatitis and prediction for the efficacy of dupilumab. [2023] Few studies have explored transcriptome of the peripheral blood mononuclear cells (PBMCs) of atopic dermatitis (AD). Parameters for prediction of the efficacy of dupilumab in AD remain obscure.

11. United States pubmed.ncbi.nlm.nih.gov

Dupilumab for Atopic Dermatitis-From Clinical Trials to Molecular and Cellular Mechanisms. [2022] Dupilumab is a monoclonal antibody that represents the first approved targeted biological therapy for adults, adolescents, and children older than 6 years with moderate-to-severe atopic dermatitis (AD). Dupilumab binds the shared chain of the interleukin-4 and interleukin-13 receptor blocking the downstream signaling of these cytokines. The clinical improvements induced by dupilumab were associated with remission of the dysregulated immune mechanisms linked with AD. Dupilumab reversed the epidermal barrier defects and improved the global molecular signature of AD. This review seeks to provide an overview on the development of dupilumab as the first target-specific biological treatment for AD, with a description of the clinical trials that have been performed in different age groups, their outcomes, and reported adverse effects. Novel aspects of dupilumab treatment, as well as the current knowledge on the molecular and cellular mechanisms underlying the treatment of AD with dupilumab, are summarized and discussed.

12. Spain pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dupilumab for the Treatment of Severe Atopic Dermatitis in Clinical Practice: A Single Center Experience. [2023] Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence.