Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis

Sponsor

University of California, San Francisco (Other)

Overall Status

Recruiting

CT.gov ID

NCT03293030

Collaborator

Regeneron Pharmaceuticals (Industry), Sanofi (Industry)

Enrollment

Location

Arm

56.2

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis Atopic Dermatitis Eczema Eczema Atopic Dermatitis and Related Conditions	Drug: Dupilumab	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis

Actual Study Start Date :

Oct 22, 2018

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

CD4+ T effector cells expressing IL-4 [12 weeks]
Percentage change from pre-treatment baseline of CD4+ T effector cells expressing IL-4 at weeks 2, 4, 12 in dupilumab-treated patients.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).