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| Name | Class |
|---|---|
| Regeneron Pharmaceuticals | INDUSTRY |
| Sanofi | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dupilumab treatment | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dupilumab | Drug | Dupilumab treatment |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in CD4+ T Effector Cells Expressing IL4 in Dupilumab-treated Subjects at Week 12 vs Week 0 | The percent change in CD4+ T effector cells expressing IL-4 in dupilumab-treated subjects at week 12 vs week 0 was calculated as follows. A single value was derived for the entire population with pooled samples from pre- and post-intervention time points, which was then used to calculate a percent change between the two periods. Specifically, the mean M1 across subjects of the percentage of CD4+ T effector cells expressing IL4 was computed at week 0. The mean M2 across subjects of the percentage of CD4+ T effector cells expressing IL4 was computed at week 12. The final result was calculated as: (M1-M2)/M1*100. Therefore, the result is a number and there is no central tendency metric. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Differentially Expressed Genes in Cutaneous CD4+ T Cells Between Week 0 and Week 12 in Dupilumab-treated Subjects | A single value was derived for the entire population with pooled samples from pre- and post-intervention time points, which was then used to calculate an percent change between the two periods. Specifically, single cell RNA-sequencing was used to calculate the number of differentially expressed genes in cutaneous CD4+ T cells between week 0 and week 12 in dupilumab-treated subjects. The calculation was performed in the software package Seurat (RRID:SCR_016341) using the FindMarkers function, which utilizes a non-parametric Wilcoxon rank-sum test. Genes were considered significantly differentially expressed if the adjusted p-value < 0.05 and the absolute value of log2(Fold Change) > 1.0. Therefore, this measure is reported as a number and there is no central tendency metric. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wilson Liao, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Psoriasis and Skin Treatment Center | San Francisco | California | 94118 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dupilumab Treatment | Single group study. Approximately 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 as well as skin and stool microbiome sampling and patch testing and different points of the study. Dupilumab: Dupilumab treatment After completion of the study, 17 were enrolled and 14 participants total completed the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dupilumab Treatment | 14 subjects competed (3 withdrew during course of study). Subjects will received dupilumab for a treatment period of 52 weeks (i.e. last injection on week 50). All subjects will undergo skin biopsies for molecular profiling. Dupilumab: Dupilumab treatment |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in CD4+ T Effector Cells Expressing IL4 in Dupilumab-treated Subjects at Week 12 vs Week 0 | The percent change in CD4+ T effector cells expressing IL-4 in dupilumab-treated subjects at week 12 vs week 0 was calculated as follows. A single value was derived for the entire population with pooled samples from pre- and post-intervention time points, which was then used to calculate a percent change between the two periods. Specifically, the mean M1 across subjects of the percentage of CD4+ T effector cells expressing IL4 was computed at week 0. The mean M2 across subjects of the percentage of CD4+ T effector cells expressing IL4 was computed at week 12. The final result was calculated as: (M1-M2)/M1*100. Therefore, the result is a number and there is no central tendency metric. | Number of subjects with atopic dermatitis with single cell data | Posted | Number | Percent change | 12 weeks |
|
Through study completion, up to 52 weeks.
Patient reported
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dupilumab Treatment | 14 subjects competed (3 withdrew during course of study). Subjects will received dupilumab for a treatment period of 52 weeks (i.e. last injection on week 50). All subjects will undergo skin biopsies for molecular profiling. Dupilumab: Dupilumab treatment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eye irritation | Eye disorders | Non-systematic Assessment | Patients describing dry, itchy, irritated, red, or crusty eyes. Patient reported. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wilson Liao | University of California San Francisco | 415-476-8364 | wilson.liao@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 8, 2020 | Dec 24, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| D004485 | Eczema |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
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| ID | Term |
|---|---|
| C582203 | dupilumab |
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| 12 weeks |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| EASI score | Eczema area and severity index (EASI) is used to estimate eczema severity using 4 components: erythema, edema/papulation, lichenification, and excoriation graded from 0(none)-3(severe). Area affected is estimated in the 4 body regions separately (head/neck, upper extremities, trunk, lower extremities) and assigned an area score: 1 (1%-9%), 2 (10%-29%), 3 (30%-49%), 4 (50%-69%), 5 (70%-89%), or 6 (90%-100%). Total scores range from 0 (clear) to 72 (most severe), to be interpreted as follows: Almost clear: 0-1.1 Mild: 1.1-7.0 Moderate: 7.1-21.0 Severe: 21.1-50.0 Very severe: 50.0-72.0 | Mean | Full Range | units on a scale |
|
14 subjects competed (3 withdrew during course of study). Subjects will received dupilumab for a treatment period of 52 weeks (i.e. last injection on week 50). All subjects will undergo skin biopsies for molecular profiling.
Dupilumab: Dupilumab treatment
|
|
| Secondary | Number of Differentially Expressed Genes in Cutaneous CD4+ T Cells Between Week 0 and Week 12 in Dupilumab-treated Subjects | A single value was derived for the entire population with pooled samples from pre- and post-intervention time points, which was then used to calculate an percent change between the two periods. Specifically, single cell RNA-sequencing was used to calculate the number of differentially expressed genes in cutaneous CD4+ T cells between week 0 and week 12 in dupilumab-treated subjects. The calculation was performed in the software package Seurat (RRID:SCR_016341) using the FindMarkers function, which utilizes a non-parametric Wilcoxon rank-sum test. Genes were considered significantly differentially expressed if the adjusted p-value < 0.05 and the absolute value of log2(Fold Change) > 1.0. Therefore, this measure is reported as a number and there is no central tendency metric. | Number of subjects with atopic dermatitis with single cell data available | Posted | Number | differentially expressed genes | 12 weeks |
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| 0 |
| 17 |
| 0 |
| 17 |
| 10 |
| 17 |
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| Deep root cavity | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Patient had cavity treated and resolved with dental care |
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| migraine | Nervous system disorders | Non-systematic Assessment |
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| Oral/facial herpes simplex | Infections and infestations | Non-systematic Assessment |
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| upper respiratory illness not otherwise defined | Infections and infestations | Non-systematic Assessment |
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| COVID19 (moderate) | Infections and infestations | Non-systematic Assessment |
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| Right ear hearing loss 2/2 Meniere's Disease | Ear and labyrinth disorders | Non-systematic Assessment |
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| Facial dermatitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
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| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Note: Our statistical test was run to identify the number of significant genes. The result is a number and there is no calculation of any comparative statistic such as an odds ratio.