Atopic Dermatitis Eczema
Conditions
Interventions
Investigational product: Histamine dihydrochloride
Non-investigational product: Cetirizine 10 mg
or placebo
Sponsors
Maruho Co., Ltd
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: All participants 1. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum weight of 50 kg; 2. Fitzpatrick skin type I-II (Caucasian); 3. All subjects must use effective contraception for the duration of the study; 4. Able and willing to give written informed consent and to comply with the study restrictions. Healthy volunteers 5. Healthy male subjects, 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, blood serology and urinalysis; AD patients 6. Male and female subjects with mild to moderate AD (IGA 2 or 3) 18 to 65 years of age, inclusive. The health status is verified by absence of evidence of any clinically significant active or uncontrolled chronic disease other than AD following a detailed medical history and a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, blood serology and urinalysis; 7. Diagnosed with AD according to the Hanifin & Rajka diagnostic criteria; 8. Suitable target of the affected skin defined as an eczema lesion of at least 1% BSA for each lesions (volar forearms and/or preferably upper back, total 3 lesions) 9. IGA 2 or 3 10. VAS itch of
Exclusion criteria
Exclusion criteria: All participants 1. Diseases associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients; 2. History of pathological scar formation (keloid, hypertrophic scar); 3. Excessive sun exposure or a tanning booth within 3 weeks of enrollment 4. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year; 5. Loss or donation of blood over 500 mL within three months prior to screening. Or the donation of plasma within 14 days prior to screening; 6. Current smoker and/or regular user of other nicotine-containing products (e.g., patches); 7. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen. 8. Use of antihistamines within 3 weeks prior to start of the study; 9. Subjects who show skin reaction to Skin marker; 10. Subject has a body temperature of >=38.0 °C at any visit. Healthy volunteers 11. Subjects suffering from chronic itch defined as presence of pruritic symptoms lasting more than 6 weeks; 12. Have known history of atopy; 13. Have any current and / or recurrent pathologically, clinically significant skin condition at the treatment area (i.e. atopic dermatitis); AD patients 14. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study; 15. Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding.;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability / safety endpoints • Monitoring adverse events • Monitoring HR, BP and temperature • Local tolerance (Visual Analog Scale (VAS) pruritus) Pharmacodynamic endpoints The injection sites will be monitored for a period of up to 180 min. Safety assessments and non-invasive efficacy assessments (imaging) will be performed at baseline, directly after histamine and saline administration after 10, 30 and 60 minutes. Imaging measurements (Part A + Part C) - Perfusion by Laser speckle contrast imaging (LSCI) - Erythema by Antera 3D camera - Wheal and flare by Antera 3D camera - Wheal and flare by clinical evaluation (erythema grading scale) - Erythema by colorimetry (DSM III) Biochemical measurements - Skin biopsies (Part C). Readout measures may comprise, but are not limited to: o Immunohistochemistry: - Eosinophils - Monocytes/macrophages - Mast cells - IgE, IgG o qPCR (exploratory): - NAV 1.1 to 1.9 expression Subject reported outcomes Itch intensity is assessed on a horizontal bar from 0 to 100 representing the visual analogue scale (VAS) in both parts following each provocation every minute up to 15 minutes. After 15 minutes, itch will be assessed with a frequency of 5 minutes up to 30 min after challenge. The burning sensation is evaluated similarly. Pain intensity is assessed on a 100 mm visual analogue scale (VAS) in both parts following each provocation pre-dose, post-dose, after 10 and 30 minutes of histamine challenge Itch intensity is assessed on a horizontal bar from 0 to 100 representing the visual analogue scale (VAS) in all three parts. After every histamine/NaCl administration itch is assessed every minute up to 15 minutes. After 15 minutes, itch will be measured with a frequency of 5 minutes up to 30 min after challenge. Additionally, itch will also be assessed after 45 min and 60 min of challenge (only part A and part B). Pain intensity is assessed on a 100 mm visual analogue scale (VAS) in each part of th | — |
Secondary
| Measure | Time frame |
|---|---|
| N.a. | — |
Countries
Netherlands
Outcome results
None listed