Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis
Primary Purpose
Atopic Dermatitis, Atopic Dermatitis Eczema, Eczema
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Dupilumab
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis focused on measuring atopic dermatitis, eczema, dupilumab, atopic eczema
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).
Sites / Locations
- UCSF Psoriasis and Skin Treatment CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dupilumab treatment
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Microbiome
Microbiome samples from skin and stool at weeks 0, 2, 4, 12, and 52 will be banked for future analysis.
Full Information
NCT ID
NCT03293030
First Posted
September 21, 2017
Last Updated
January 25, 2023
Sponsor
University of California, San Francisco
Collaborators
Regeneron Pharmaceuticals, Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT03293030
Brief Title
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
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 22, 2018 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Regeneron Pharmaceuticals, Sanofi
4. Oversight
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
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis, Atopic Dermatitis Eczema, Eczema, Atopic Dermatitis and Related Conditions
Keywords
atopic dermatitis, eczema, dupilumab, atopic eczema
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dupilumab treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Other Intervention Name(s)
Dupixent
Intervention Description
Dupilumab treatment
Primary Outcome Measure Information:
Title
CD4+ T effector cells expressing IL-4
Description
Percentage change from pre-treatment baseline of CD4+ T effector cells expressing IL-4 at weeks 2, 4, 12 in dupilumab-treated patients.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Number of differentially expressed genes and pathways
Description
Number of differentially expressed genes and pathways in each cell population at weeks 2, 4, 12 compared to pre-treatment baseline using RNA-seq.
Time Frame
12 weeks
Title
Microbiome
Description
Microbiome samples from skin and stool at weeks 0, 2, 4, 12, and 52 will be banked for future analysis.
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mimi Chung
Phone
415-476-4019
Email
mimi.chung@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wilson Liao, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSF Psoriasis and Skin Treatment Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94118
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Quinn Thibodeaux, MD
Phone
415-944-7618
Email
psoriasis@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Wilson Liao, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Immunogenetic Profiling of Dupilumab for the Treatment of Atopic Dermatitis
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