Longitudinal Endotyping Of Atopic Dermatitis Through Transcriptomic Skin Analysis

NCT05436535 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: DAIT ADRN-12
• Study Type: interventional
• Target: 433
• Locations: 1 country
• Sites: 10

Brief 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

Outcome Measures

Primary Outcomes (1)

• 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 in the dupilumab-naïve AD adults and children.

  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.

  At Day 7

Secondary Outcomes (3)

• Normalized gene counts expressed in non-lesional skin transcriptome between non-AD vs. mild dupilumab-naïve AD adults and children.

  At Day 7 and Days 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.

  At Day 7 and Days 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.

  At Day 7 and Days 168-224 (End of Study)

Study Arms (3)

Dupilumab-naïve atopic dermatitis participants

EXPERIMENTAL

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.

Biological: Dupilumab; Drug: Vanicream- Dupilumab-naïve; Drug: Triamcinolone Acetonide; Drug: Hydrocortisone

Experienced Dupilumab atopic dermatitis participants

EXPERIMENTAL

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).

Drug: Vanicream- Experienced Dupilumab

Non-atopic dermatitis participants

ACTIVE COMPARATOR

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).

Drug: Vanicream- Active

Interventions

Dupilumab BIOLOGICAL

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).

Also known as: Dupixent

Dupilumab-naïve atopic dermatitis participants

Vanicream- Dupilumab-naïve DRUG

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.

Dupilumab-naïve atopic dermatitis participants

Triamcinolone Acetonide DRUG

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.

Dupilumab-naïve atopic dermatitis participants

Hydrocortisone DRUG

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.

Dupilumab-naïve atopic dermatitis participants

Vanicream- Active DRUG

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.

Non-atopic dermatitis participants

Vanicream- Experienced Dupilumab DRUG

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.

Experienced Dupilumab atopic dermatitis participants

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All Participants:
• Participant and/or parent guardian must be able to understand and provide informed consent and assent (if applicable)
• Male or female, 6 years of age or older inclusive at the Screening Visit
• Participants must agree to apply a stable dose of a study provided topical moisturizer (Vanicream (TM)) at least twice daily between the Baseline Assessment and Day 7 Visits to a specified skin target area
• Individuals with asthma must adhere to asthma controller medication(s) for the duration of the study
• Individuals who can become pregnant, as defined in the study manual of procedures, must have a negative pregnancy test at the Baseline Assessment and Day 7 Visits if they do not self-report as pregnant.
• Individuals who can become pregnant, as defined in the study manual of procedures, must meet either of the following criteria prior to Baseline Assessment:
• Willing to remain abstinent from intercourse that may result in pregnancy.
• Willing to use Food and Drug Administration (FDA) approved methods of contraception for the duration of the study
• Participant and/or parent guardian must be able to understand and complete study-related questionnaires.
• Participants must have adequate sizes of non-lesional skin on extremities or trunk.
• Non-Atopic dermatitis (AD) Participants:
• No history of AD or food allergy as diagnosed by a physician
• All AD Participants (DNAD and LTD):
• DNAD and LTD participants must have a history of chronic AD, (according to the Atopic Dermatitis Research Network \[ADRN\] Standard Diagnostic Criteria \[Appendix B\]), that has been present for at least 1 year before the Screening Visit.

You may not qualify if:

• Inability or unwillingness of a participant or parent guardian to comply with study protocol
• Have a genetic relative (e.g., parent, sibling, grandchild, half-sibling) or household member (e.g., spouse) already enrolled in the study
• Weight less than 15 kg
• Known systemic hypersensitivity to any of the excipients of the study treatments (Vanicream (TM), hydrocortisone, triamcinolone, or dupilumab)
• Have any skin disease other than Atopic dermatitis (AD) that might compromise the stratum corneum barrier (e.g., bullous diseases, psoriasis, cutaneous T cell lymphoma \[also called Mycosis Fungoides or Sezary syndrome\], dermatitis herpetiformis, Hailey-Hailey, or Darier's disease)
• Known or suspected immunosuppression, including history of invasive opportunistic infections (e.g. tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, aspergillosis) despite infection resolution, or otherwise recurrent immune-compromised status, as judged by investigator
• Known history of human immunodeficiency virus (HIV) infection
• Ocular disorder that in the opinion of the investigator could adversely affect the individual's risk for study participation. Examples include, but are not limited to, individuals with a history of or active case of herpes keratitis; Sjogren's Syndrome, Keratoconjunctivitis Sicca, or Dry Eye Syndrome that require daily use of supplemental lubrication; or individuals with ocular conditions that require the regular use of ocular corticosteroids or cyclosporine
• Parasitic infection, except for vaginal trichomoniasis, within 12 months of the Screening Visit, or high risk for contracting parasitic infections (e.g. living in or traveling to endemic areas)
• History of non-malignant lymphoproliferative disorders
• History of alcohol or drug abuse within 2 years before the Screening Visit
• History of hypersensitivity to local anesthetics (e.g., lidocaine or Novocain), bleeding disorders, or treatment with anticoagulants or other conditions in adult participants that would make the biopsy procedure inadvisable
• History of serious life-threatening reaction to tape or adhesives
• Individuals with asthma who have required use of a systemic corticosteroid within 3 months prior to the Baseline Assessment Visit or who require a dose greater than 880 mcg/day of fluticasone propionate or equivalent inhaled corticosteroid to maintain asthma control.
• Planned major surgical procedure during study participation that could affect study participation or outcome assessment, per PI discretion

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (10)

University of California, San Diego: Dermatology Clinical Trials Unit

La Jolla, California, 92093, United States

Location

Children's Hospital Los Angeles: Division of Clinical Immunology & Allergy

Los Angeles, California, 90027, United States

Location

National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

Denver, Colorado, 80206, United States

Location

Boston Children's Hospital: Department of Immunology

Boston, Massachusetts, 02215, United States

Location

Icahn School of Medicine at Mount Sinai: Department of Pediatrics Allergy & Immunology

New York, New York, 10029, United States

Location

University of Rochester Medical Center: Department of Dermatology

Rochester, New York, 14642, United States

Location

North Carolina Children's Hospital: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center: Asthma Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health & Science University: Department of Dermatology

Portland, Oregon, 97239, United States

Location

University of Pennsylvania, Perelman Center for Advanced Medicine: Department of Dermatology

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Division of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases (NIAID)

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

dupilumab; Triamcinolone Acetonide; Hydrocortisone

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Donald Leung, M.D., Ph.D.

  National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

  STUDY CHAIR

• Max A. Seibold, Ph.D.

  National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: June 29, 2022
• Study Start: November 21, 2022
• Primary Completion: April 7, 2025
• Study Completion: October 24, 2025
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (10)