Longitudinal Endotyping Of Atopic Dermatitis Through Transcriptomic Skin Analysis

Summary

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.

Conditions

• Atopic Dermatitis

Interventions

BIOLOGICAL

Dupilumab

Adult dupilumab-naïve topical steroid non-responder (EASI \>7) participants beginning treatment with dupilumab will initially receive a loading dose of two 300 mg subcutaneous injections. The two injections will be administered at different sites in the abdomen, thighs, or upper arms. Pediatric dupilumab-naïve topical steroid non-responder participants beginning treatment with dupilumab will receive a loading dose, according to their weight. Dupilumab-naïve topical steroid non-responsive participants will continue use of dupilumab on a schedule determined by their age and weight until their penultimate scheduled visit (Day 140-196).

DRUG

Vanicream- Dupilumab-naïve

Dupilumab-naïve AD participants will apply Vanicream at least twice daily to the specified target skin area over two time periods during the study. First, they will apply starting at Day 0 through Day 7. They will resume application starting at their penultimate visit (Day 140-196) through the End of Study Assessment.

DRUG

Triamcinolone Acetonide

On Day 7, all dupilumab-naïve AD participants will begin applying triamcinolone 0.1% ointment (provided by the study) twice daily to the specified target area. Additionally, dupilumab-naïve AD participants will apply triamcinolone 0.1% ointment twice daily to active lesions on non-sensitive, non-target skin. Between Day 35 and Day 140, dupilumab-naïve AD topical steroid responsive (EASI ≤ 7) participants will apply triamcinolone 0.1% ointment (provided by the study) once or twice daily, per clinician discretion, to the specified target area. Additionally, participants will apply triamcinolone 0.1% ointment once or twice daily, per clinician discretion, to active lesions on non-sensitive skin body wide. Between Day 35 and Day 140, dupilumab-naïve topical steroid non-responder (EASI \>7) participants may apply triamcinolone 0.1% ointment as needed to active lesions on non-sensitive, non-target skin.

DRUG

Hydrocortisone

On Day 7, all dupilumab-naïve AD participants will apply hydrocortisone 2.5% ointment twice daily to active lesions on sensitive, non-target skin. Between Day 35 and Day 140, dupilumab-naïve AD topical steroid responsive (EASI ≤ 7) participants will apply hydrocortisone 2.5% ointment once or twice daily, per clinician discretion, to active lesions on sensitive skin body wide. Between Day 35 and Day 140, dupilumab-naïve topical steroid non-responder (EASI \>7) participants may apply hydrocortisone 2.5% ointment as needed to active lesions on sensitive, non-target skin.

DRUG

Vanicream- Active

Non-AD control participants will apply Vanicream at least twice daily to the specified target skin area over two time periods during the study. First, they will apply starting at Day 0 through Day 7. They will resume application starting at Day 140 through the End of Study Assessment Visit.

DRUG

Vanicream- Experienced Dupilumab

Long-term dupilumab participants will apply Vanicream at least twice daily to the specified target skin area over two time periods during the study. First, they will apply starting at Day 0 through Day 7. They will resume application starting at Day 140 through the End of Study Assessment Visit.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Donald Leung, M.D., Ph.D. · National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

• Max A. Seibold, Ph.D. · National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-11-21

Primary Completion

2025-04-07

Completion

2025-10-24

FDA Drug

Yes

Countries

• United States

Study Locations