Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis

Atopic Dermatitis Clinical Trial

Official title:

Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03293030
• Other study ID #: Dupilumab Immunogenetics
• Status: Recruiting
• Phase: Phase 4
• Start date: October 22, 2018
• Est. completion date: June 30, 2024

Study information

• Verified date: March 2024
• Source: University of California, San Francisco
• Contact: Mimi Chung
• Phone: 415-476-4019
• Email: mimi.chung[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: June 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-?, 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).

Related Conditions & MeSH terms

• Atopic Dermatitis
• Atopic Dermatitis and Related Conditions
• Atopic Dermatitis Eczema
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Dupilumab
Dupilumab treatment

Locations

Country	Name	City	State
United States	UCSF Psoriasis and Skin Treatment Center	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	Regeneron Pharmaceuticals, Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Microbiome	Microbiome samples from skin and stool at weeks 0, 2, 4, 12, and 52 will be banked for future analysis.	52 weeks