Longitudinal Endotyping Of Atopic Dermatitis Through Transcriptomic Skin Analysis (ADRN-12)
Overview
- Phase
- Phase 4
- Intervention
- Dupilumab
- Conditions
- Atopic Dermatitis
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 433
- Locations
- 13
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 2 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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 malignancy within 5 years before the Screening Visit (completely treated in situ carcinoma of the cervix, and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin or melanoma in situ are not exclusionary)
Arms & Interventions
Dupilumab-naïve atopic dermatitis participants
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.
Intervention: Dupilumab
Dupilumab-naïve atopic dermatitis participants
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.
Intervention: Vanicream- Dupilumab-naïve
Dupilumab-naïve atopic dermatitis participants
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.
Intervention: Triamcinolone Acetonide
Dupilumab-naïve atopic dermatitis participants
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.
Intervention: Hydrocortisone
Experienced Dupilumab atopic dermatitis participants
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).
Intervention: Vanicream- Experienced Dupilumab
Non-atopic dermatitis participants
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).
Intervention: Vanicream- Active
Outcomes
Primary Outcomes
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.
Time Frame: At Day 7
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.
Secondary Outcomes
- 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))