Atopic Dermatitis
Conditions
Keywords
atopic dermatitis, elidel, pimecrolimus, CASM981, immunity, cathelicidin, antimicrobial peptide, eczema
Brief summary
The purpose of this study is to determine the effect of topical pimecrolimus on the immune system by assessing the levels of antimicrobial peptides in the skin of patients with eczema. It is hypothesized that pimecrolimus applied topically will repair the body's immune system in patients with eczema by increasing antimicrobial peptides.
Detailed description
Patients with atopic dermatitis (AD) have higher rates of skin infections from viruses and bacteria. They also have an impaired innate immune system. Antimicrobial peptides are a component of the innate immune system which are decreased in atopics. In vitro, pimecrolimus has demonstrated its ability to increase antimicrobial peptides. This study will examine the ability of pimecrolimus to increase antimicrobial peptides in vivo in AD patients. Thus, the study will yield a better understanding of the role of pimecrolimus in regulating the immune system in atopics.
Interventions
DRUGPimecrolimus
20 AD patients will be given pimecrolimus 1% to apply twice daily for up to three weeks on each lesional site predetermined at baseline. Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).
OTHERVehicle cream
20 AD patients will be treated with vehicle cream twice daily for up to 3 weeks on each lesional site predetermined at baseline. Lesional target site and non-lesional site will be determined at Visit 1. Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit).
Sponsors
Novartis
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-70 years 2. Target lesion IGA ≥2 3. Target IGA=0 (for non-lesional site) 4. Male or female of any race and ethnicity 5. Chronic AD for more than one year duration 6. Subject of child-bearing potential must be willing to practice effective birth control during the study 7. Subject agrees to comply with study requirements and attend all required visits.
Exclusion criteria
1. Patients ≥ 18 years of age with only AD of the face 2. Women of childbearing potential not using the contraception method(s) specified in this study (abstinence, IUD, diaphragm, oral contraceptives) 3. Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study 4. Hypersensitivity to pimecrolimus cream or any excipient of the cream 5. Subject has a skin disorder in addition to dermatitis in the areas to be treated 6. Subject has Netherton's syndrome or other genodermatoses that result in a defective epidermal barrier 7. Pregnant or nursing females 8. Immunocompromised patient (e.g., lymphoma, HIV/AIDS, Wiskott-Aldrich Syndrome), or with a history of active or malignant disease (excluding non-melanoma skin cancer) 9. History of psychiatric disease or history of alcohol or drug abuse that would interfere with the ability to comply with the study protocol 10. Patients known to be non-compliant with a medication regimen 11. Subjects with significant concurrent medical condition(s) at screening that in the view of the investigator prohibits participation in the study (e.g., severe concurrent allergic disease, condition associated with malignancy, and condition associated with immunosuppression) 12. Active viral or fungal skin infections at the target areas 13. Previous participation in this study 14. Ongoing participation in another investigational trial 15. Use of any oral or topical antibiotic during the study and up to one week prior to entering the study 16. Use of any local therapy for AD less than one week prior to screening 17. Use of any systemic immunosuppressive therapy for AD less than four weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cathelicidin mRNA Expression Levels in Adult Skin From Patients With AD | 3 weeks | Delta-delta CT values were measured using RT-PCR of cathelicidin mRNA in human biopsy samples at baseline, and then 3 weeks after treatment with either pimecrolimus or placebo |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pimecrolimus Pimecrolimus: 20 AD patients will be given pimecrolimus 1% to apply twice daily for up to three weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1.
Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit). | 20 |
| Vehicle Cream Vehicle cream: 20 AD patients will be treated with vehicle cream twice daily for up to 3 weeks on each lesional site predetermined at baseline. AD severity will be evaluated by the Investigator Global Assessment of Disease Activity (IGA). The IGA scale is 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe disease9. The patient's AD will be evaluated on Visit 1 (Day -14 to 1), Visit 2 (Day 1), and Visit 3 (Week 21). Lesional target site and non-lesional site will be determined at Visit 1.
Two 2 mm biopsies will be obtained from a target AD lesion and non-lesional sites at Visit 2, and Visit 3 (four biopsies each visit). | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Pimecrolimus | Vehicle Cream | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 40 Participants |
| Age, Continuous | 26.2 years STANDARD_DEVIATION 8.4 | 28.6 years STANDARD_DEVIATION 9.5 | 27.4 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex/Gender, Customized Female | 7 participants | 7 participants | 14 participants |
| Sex/Gender, Customized Male | 9 participants | 6 participants | 15 participants |
| Sex/Gender, Customized Unknown | 4 participants | 7 participants | 11 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Cathelicidin mRNA Expression Levels in Adult Skin From Patients With AD
Delta-delta CT values were measured using RT-PCR of cathelicidin mRNA in human biopsy samples at baseline, and then 3 weeks after treatment with either pimecrolimus or placebo
Time frame: 3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pimecrolimus | Cathelicidin mRNA Expression Levels in Adult Skin From Patients With AD | .0016 delta-delta ct units on PCR | Standard Error 0.002 |
| Vehicle Cream | Cathelicidin mRNA Expression Levels in Adult Skin From Patients With AD | .0024 delta-delta ct units on PCR | Standard Error 0.004 |