Clinical trial NCT03293030: Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis
Official title: Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atopic Dermatitis
Atopic Dermatitis Eczema
Eczema
Atopic Dermatitis and Related Conditions
Keywords: atopic dermatitis
eczema
dupilumab
atopic eczema
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
name: Sanofi
First posted: 2017-09-26
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: CD4+ T effector cells expressing IL-4
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of differentially expressed genes and pathways
timeFrame: 12 weeks
measure: Microbiome
timeFrame: 52 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Psoriasis and Skin Treatment Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Wilson Liao, MD
role: PRINCIPAL_INVESTIGATOR
References: