Clinical trial NCT05268107: Ethnic Differences in Mechanisms of Action of Dupilumab
Official title: Ethnic Differences in Mechanisms of Action of Dupilumab
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Atopic Dermatitis
Keywords: Asian patients
African American patients
Caucasian patients
Inflammatory responses
Dupixent
Dupilumab
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2022-03-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A total of 10 Caucasian, 10 Asian (Eastern and Southeastern Asian), and 10 African American patients with moderate-to severe AD (5 males and 5 females in each group) will be enrolled.
Primary purpose: BASIC_SCIENCE

Brief summary: Previous research has shown that Asian and African Americans are more likely to develop atopic dermatitis (AD) than their Caucasian counterparts. However, limited information is known about AD in Asian and African American populations because most molecular studies have focused on Caucasians with AD.

This trial will determine differences in inflammatory responses to dupilumab between Caucasian, Asian, and African American patients with AD.

The central hypothesis of this study is that ethnic differences in both immune and stromal cells contribute to variability in AD presentation and response to anti-interleukin-4 receptor (IL-4R) inhibition with dupilumab.


Eligibility criteria: Inclusion Criteria:

* Established diagnosis of AD for at least 2 years before the screening visit and confirmed according to the American Academy of Dermatology Consensus Criteria at the time of the screening visit
* Moderate-to-severe AD with involvement \> 10% of body-surface-area (BSA) and investigator global assessment (IGA) score 3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both the screening and baseline visits
* Female subjects of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) must agree either to commit to true abstinence throughout the study and for 12 weeks after the last study drug injection or to use an adequate and approved method of contraception throughout the study and for 12 weeks after the last study drug injection
* Subject willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol

Exclusion Criteria:

* Body weight less than 30 kilogram
* Subjects meeting 1 or more of the following criteria at screening or baseline:

  1. Had an exacerbation of asthma requiring hospitalization in the preceding 12 months.
  2. Reporting asthma that has not been well-controlled (ie, symptoms occurring on \>2 days per week, nighttime awakenings 2 or more times per week, or some interference with normal activities) during the preceding 3 months
  3. Asthma Control Test (ACT) \< 19 (only for subjects with a history of asthma).
  4. Subjects with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis.
* Cutaneous infection within 1 week before the baseline visit, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before the baseline visit.
* Confirmed or suspected coronavirus disease 2019 (COVID-19) infection within 4 weeks before the screening or baseline visit
* Received COVID-19 vaccination within 4 weeks before baseline visit
* Previous treatment with dupilumab
* Pregnant women (positive serum pregnancy test result at the screening visit or positive urine pregnancy test at the baseline visit), breastfeeding women, or women planning a pregnancy during the clinical study
* History of lymphoproliferative disease or history of malignancy of any organ system within the last 5 years, except for basal cell carcinoma, squamous cell carcinoma in situ (Bowen's disease), or carcinomas in situ of the cervix that have been treated and have no evidence of recurrence in the last 12 weeks before the baseline visit
* History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, i.e., monoclonal antibody) or to lidocaine
* Known active or latent tuberculosis (TB) infection
* Known or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment
* History of or current confounding skin condition (i.e., Netherton syndrome, psoriasis, cutaneous T-cell lymphoma \[mycosis fungoides or Sezary syndrome\], contact dermatitis, chronic actinic dermatitis, dermatitis herpetiformis)
* Planned or expected major surgical procedure during the study
* Currently participating or participated in any other study of a drug or device, within the past 8 weeks before the screening visit, or is in an exclusion period (if verifiable) from a previous study
* History of alcohol or substance abuse within 6 months of the screening
* History of poor wound healing or keloid formation

Primary outcomes:
measure: Difference in inflammatory response to dupilumab between Caucasian, Asian and African American patients with atopic dermatitis as measured by change in expression of interleukin4 (IL4) from week 0 to 2.
timeFrame: Week 0, week 2
Secondary outcomes:
measure: Difference in inflammatory response to dupilumab between Caucasian, Asian and African American patients with atopic dermatitis as measured by change in expression of interleukin13 from week 0 to 2.
timeFrame: Week 0, week 2
measure: Difference in inflammatory response to dupilumab between Caucasian, Asian and African American patients with atopic dermatitis as measured by change in expression of Interferon (IFN) from week 0 to 2.
timeFrame: Week 0, week 2
measure: Difference in inflammatory response to dupilumab between Caucasian, Asian and African American patients with atopic dermatitis as measured by change in expression of interleukin36 from week 0 to 2.
timeFrame: Week 0, week 2
measure: Difference in inflammatory response to dupilumab between Caucasian, Asian and African American patients with atopic dermatitis as measured by change in expression of interleukin4 from week 0 to 16.
timeFrame: Week 0 to week 16
measure: Difference in inflammatory response to dupilumab between Caucasian, Asian and African American patients with atopic dermatitis as measured by change in expression of interleukin13 from week 0 to 16.
timeFrame: Week 0 to week 16
measure: Difference in inflammatory response to dupilumab between Caucasian, Asian and African American patients with atopic dermatitis as measured by change in expression of IFN from week 0 to 16.
timeFrame: Week 0 to week 16
measure: Difference in inflammatory response to dupilumab between Caucasian, Asian and African American patients with atopic dermatitis as measured by change in expression of interleukin36 from week 0 to 16.
timeFrame: Week 0 to week 16
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Johann Gudjonsson, MD
role: PRINCIPAL_INVESTIGATOR
References: