Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis

This is a single-arm, open-label study to examine the effect of dupilumab on the immunologic and genetic environment within atopic dermatitis skin lesions.

Study Overview

• Status: Recruiting
• Conditions: Eczema; Atopic Dermatitis; Atopic Dermatitis Eczema; Atopic Dermatitis and Related Conditions
• Intervention / Treatment: Drug: Dupilumab

Detailed Description

Fifteen subjects with moderate to severe AD will receive dupilumab for a treatment period of 52 weeks (i.e. last injection on week 50). Biopsy samples from AD subjects and surgical discard samples will undergo molecular profiling. Skin swabs and stool samples will be collected and banked for future analysis. The reason to treat patients for 52 weeks is to have the ability to correlate early molecular events with clinical outcomes at week 52.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mimi Chung; Phone Number: 415-476-4019; Email: mimi.chung@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94118
      • Recruiting
      • UCSF Psoriasis and Skin Treatment Center
      • Contact: Quinn Thibodeaux, MD; Phone Number: 415-944-7618; Email: psoriasis@ucsf.edu
      • Principal Investigator: Wilson Liao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to provide written informed consent and comply with the protocol.
• At least 18 years of age.
• Diagnosis of chronic atopic dermatitis for at least 3 years prior to enrollment.
• Subject is considered a candidate for phototherapy or systemic therapy
• Eczema Area and Severity Index (EASI) score ≥ 16
• Investigator Global Assessment (IGA) ≥ 3
• 10% body surface area (BSA) or greater
• Subject is unlikely to conceive due to male, post-menopausal, or using adequate contraceptive (barrier, hormonal, implant, or permanent sterilization methods).
• Physical exam within clinically acceptable limits.

Exclusion Criteria:

• Subject is unable to provide written informed consent or comply with the protocol.
• Subject is younger than 18 years of age.
• Subject has had atopic dermatitis for less than 3 years prior to enrollment.
• Subject with mild atopic dermatitis (EASI<16 and IGA<3) or is not a candidate for phototherapy or systemic treatments.
• Subject with current, or a history of, severe atopic dermatitis well controlled on current therapy.
• Serious known infection.
• History of immunosuppression (including human immunodeficiency virus (HIV))
• History of malignancy within 5 years before the screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
• Severe concomitant illnesses.
• Having used immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.) or phototherapy within 4 weeks before the baseline visit.
• Treatment with topical corticosteroid or topical calcineurin inhibitor within 1 week before the baseline visit.
• Treatment with any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever is longer, or use of other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever is longer.
• Physical or laboratory exam not within clinically acceptable limits.
• Subjects possess other diagnoses that, in the investigator's opinion, preclude him/her from safely participating in this study or interfere with the evaluation of the subject's atopic dermatitis.
• History of known or suspected intolerance to any of the ingredients of the investigational study product.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>10 mIU/mL).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dupilumab treatment; 15 subjects will receive dupilumab for a treatment period of 52 weeks (i.e. last injection on week 50). All subjects will undergo skin biopsies for molecular profiling.	Drug: Dupilumab; Dupilumab treatment; Other Names: Dupixent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD4+ T effector cells expressing IL-4	Percentage change from pre-treatment baseline of CD4+ T effector cells expressing IL-4 at weeks 2, 4, 12 in dupilumab-treated patients.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of differentially expressed genes and pathways	Number of differentially expressed genes and pathways in each cell population at weeks 2, 4, 12 compared to pre-treatment baseline using RNA-seq.	12 weeks
Microbiome	Microbiome samples from skin and stool at weeks 0, 2, 4, 12, and 52 will be banked for future analysis.	52 weeks

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Sanofi; Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Wilson Liao, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2018
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: atopic dermatitis; eczema; dupilumab; atopic eczema
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: Dupilumab Immunogenetics

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No