Anti-inflammatory drugs in TLR7 topical challenge model

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

1. Healthy male or female 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. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects;
2. Body mass index (BMI) between 18 and 30 kg/m2 and a maximum weight of 100 kg, inclusive;
3. Fitzpatrick skin type I-II (Caucasian);
4. Subjects and their partners of childbearing potential must use effective contraception for the duration of the study;
5. Able and willing to give written informed consent and to comply with the study restrictions.

Exclusion Criteria

1. Any vaccination within the last 3 months;
2. Family history of psoriasis;
3. History of pathological scar formation (keloid, hypertrophic scar);
4. Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis);
5. Previous use of Aldara (IMQ cream) 3 weeks prior to the baseline visit
6. Known hypersensitivity to the (non)investigational drug, drugs of the same class, or any of their excipients;
7. Hypersensitivity for dermatological marker at screening;
8. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study;
9. Use of topical medication (prescription or over-the-counter [OTC]) within 30 days of study drug administration, or less than 5 half-lives (whichever is longer) in local treatment area
10. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment;
11. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year.
12. Loss or donation of blood over 500 mL within three months prior to screening
13. Any (medical) condition that would, in the opinion of the investigator, potentially compromise the safety or compliance of the patient or may preclude the patient’s successful completion of the clinical trial.
14. Latent Diabetes Mellitus
15. Volunteers with clinically relevant infections

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Tolerability / safety endpoints<br>•Adverse events (AEs)<br>• Vital signs<br>• 12-leads ECGs<br>• Local tolerance (erythema grading scale, numeric rating scale (NRS) pruritus and pain)<br><br>Pharmacodynamic endpoints<br>Non-invasive measures:<br>• Perfusion by Laser speckle contrast imaging (LSCI)<br>• Erythema by Antera 3D camera<br>• Erythema by clinical evaluation (erythema grading scale)<br>• Optical Coherence Topography (OCT)<br>• 2D photography by ATBM for photo documentation only<br><br>lnvasive measures:<br>•Suction blister exudates, including but not limited to<br> o Cytokines and chemokines<br> o Flow cytometry (neutrophils, monocytes/macrophages, CD4+ lymphocytes, CD8+ lymphocytes, CD56+ lymphocytes, CDlc dendritic cells)<br>•Skin punch biopsies<br> o Local biomarkers, including but not limited to: lL-8, IFN-a, lL-1ß, IFN-?, MXA, MX1, lL-6, lL-10, CCL20 and HBD-2<br> o lmmunohistochemistry:CD1a, HLADR, CD8+, CD4+, CD14+, CD11c<br> o Histology (HE)

Secondary Outcome Measures