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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
433
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).
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.
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.
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.
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.
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.
University of California, San Diego: Dermatology Clinical Trials Unit
La Jolla, California, United States
Children's Hospital Los Angeles: Division of Clinical Immunology & Allergy
Los Angeles, California, United States
National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
Denver, Colorado, United States
Boston Children's Hospital: Department of Immunology
Boston, Massachusetts, United States
Icahn School of Medicine at Mount Sinai: Department of Pediatrics Allergy & Immunology
New York, New York, United States
University of Rochester Medical Center: Department of Dermatology
Rochester, New York, United States
North Carolina Children's Hospital: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology
Chapel Hill, North Carolina, United States
Cincinnati Children's Hospital Medical Center: Asthma Center
Cincinnati, Ohio, United States
Oregon Health & Science University: Department of Dermatology
Portland, Oregon, United States
University of Pennsylvania, Perelman Center for Advanced Medicine: Department of Dermatology
Philadelphia, Pennsylvania, United States
Number of Dupilumab-naïve AD Participants With Mild (EASI ≤ 7) vs. Moderate-to-severe (EASI > 7) AD Severity Between Type 2-high vs. Type 2-low Endotype From Non-lesional Skin Transcriptome.
Eczema Area and Severity Index (EASI) is a composite score (range: 0-72) measuring physical signs of atopic dermatitis (AD), including area of involvement and severity. Severity components include: erythema, papulation, excoriation and lichenification \[0=absent, 1=mild, 2=moderate, 3=severe\] for each body region (head/neck, trunk, arms, legs). Area of involvement (%) is assessed for each body region. Area and severity of each body region is weighted based on size of region, and region scores are added for the total score. Scores ≤7 are considered mild AD severity, \>7 are considered moderate-to-severe.
Time frame: Day 7
Normalized Gene Counts Expressed in Non-lesional Skin Transcriptome Between Non-AD vs. Mild Dupilumab-naïve AD Adults and Children.
Gene counts are produced by whole transcriptome sequencing (WTS) on the non-lesional skin tape strips collected at Day 7 and Day 168-224 (End of Study). These counts are then normalized by variance stabilizing transformation (VST).
Time frame: Day 7, Day 168-224 (End of Study)
Normalized Gene Counts Expressed in Non-lesional Skin Transcriptome Between Non-AD vs. Moderate-to-severe Dupilumab-naïve AD Adults and Children.
Gene counts are produced by whole transcriptome sequencing (WTS) on the non-lesional skin tape strips collected at Day 7 and Day 168-224 (End of Study). These counts are then normalized by variance stabilizing transformation (VST).
Time frame: Day 7, Day 168-224 (End of Study)
Change in Normalized Gene Counts Expressed in Non-lesional Skin Transcriptome From Day 7 to Day 168-224 Among Non-AD, Topical Steroid Responders, Dupilumab Responders, Dupilumab Non-Responders, and Long-term Dupilumab AD Adults and Children.
Gene counts are produced by whole transcriptome sequencing (WTS) on the non-lesional skin tape strips collected at Day 7 and Day 168-224 (End of Study). These counts are then normalized by variance stabilizing transformation (VST). The change in normalized gene counts is calculated from Day 7 to Day 168-224 (End of Study) within each group.
Time frame: Day 7 and Day 168-224 (End of Study)
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