Challenge model Dermatological challenge model skin inflammation model
Conditions
Interventions
None listed
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male and 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, haematology, 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 minimum weight of 50 kg, inclusive; 3. Fitzpatrick skin type I-III (Caucasian); 4. Subjects and their partners of childbearing potential must use effective contraception (see paragraph 4.4.2) for the duration of the study. Women of childbearing potential are defined as all women physiologically capable of becoming pregnant, unless they meet one of the following conditions: -Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks after surgical bilateral oophorectomy with or without hysterectomy; -Post-hysterectomy. *5. Able and willing to give written informed consent and to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. History of pathological scar formation (keloid, hypertrophic scar) or keloids or surgical scars in the target treatment area of the upper back that in the opinion of the investigator, would limit or interfere with dosing and/or measurement in the trial; 2. Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis); including tattoos; 3. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel 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.* 4. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrolment or planned to use during the course of the study; 5. 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 6. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year. 7. Loss or donation of blood over 500 mL within three months prior to screening or donation of plasma within 14 days of screening 8. Any history or current presence of a (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. 9. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg at screening.* 10. Abnormal findings in the resting ECG at screening defined as:* -QTcF> 450 or 470 or *100 bpm);* -Personal or family history of congenital long QT syndrome or sudden death;* -ECG with QRS and/or T wave judged to be unfavorable for a consistently accurate QT measurement (e.g., neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves);* -Evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker.* 11. Chronic infection with HIV, hepatitis B (HBV) or hepatitis C (HCV). A positive HBV surface antigen (HBsAg) test at screening excludes a subject. 12. Presence of current or a history of ongoing, chronic or recurrent infections or infectious disease. Exception for plantar warts and onychomycosis. 13. Autoimmune disease such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis or other immune-inflammatory diseases.* 14. Hypersensitivity for dermatological marker at screening. 15. Current smoker and/or regular user of other nicotine-containing products (e.g., patches). 16. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability / safety endpoints: Adverse events (AEs) Local tolerance (erythema grading scale) Pharmacodynamic endpoints: Non-invasive measures: Perfusion by Laser speckle contrast imaging (LSCI) Erythema by Antera 3D camera Erythema by clinical evaluation (erythema grading scale) Invasive measures: Skin punch biopsies, endpoints may include, but are not limited to: Histology (HE) Immunofluorescence/immunohistochemistry: complement proteins such as C4d, C3c, C3d, C4d, Properdin, C5b-9 and cellular markers (e.g. MPO) and/or qPCR or RNA sequencing and/or protein-based assessments for local biomarkers | — |
Countries
Netherlands
Outcome results
None listed