Repeated lipopolysaccharide skin challenges Skin and Connective Tissue Diseases
Conditions
Interventions
This is a single-centre, repeated LPS challenge study to explore the effects of local intradermal LPS challenges over time in healthy volunteers. Each subject receives one LPS injection on the volar f
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male and female subjects, 18 to 45 years of age, inclusive. Healthy status is defined by the 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 enrollment 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 for the duration of the study 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 that in the opinion of the investigator, would limit or interfere with dosing and/or measurement in the trial. 2. Any current and/or recurrent pathologically, clinically significant skin condition at the treatment area (lower arm and upper back, i.e., atopic dermatitis); including tattoos. 3. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrolment or planned to use during the course of the study. 4. Known immunodeficiency 5. Use of topical medication (prescription or over-the-counter [OTC]) in the local treatment area or any medication that may interfere with the study objectives as judged by the investigator within 30 days of study drug administration, or less than 5 half-lives (whichever is longer) 6. Participation in an investigational drug or device study within 3 months, or 5 half-lives whichever is longer, prior to screening or more than four times in the past year. 7. Loss or donation of blood over 500 ml within 3 months prior to screening or donation of plasma within 14 days of screening. 8. 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. 9. Pregnant, a positive pregnancy test, intending to become pregnant during the study conduct, or breastfeeding. 10. Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody (HCV ab), or human immunodeficiency virus antibody (HIV ab) at screening. 11. A history of ongoing, chronic or recurrent infectious disease 12. Hypersensitivity for dermatological marker at screening 13. Current smoker and/or regular user of other nicotine-containing products (e.g., patches) 14. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen. 15. Presence of current, clinically relevant infections 16. Any vaccination within the last 4 weeks before day 1. Intention to receive any vaccination(s) before the last day of follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety 1.1. Treatment-emergent (serious) adverse events ((S)AEs) 1.2. Safety labs tests (acute phase proteins (CRP), leukocyte differentiation at Study day 1: baseline + 24 hours post dose; Study day 15: baseline + 24 hours post dose; Study day 29: baseline + 24 hours post dose; Study day 37 follow-up visit, once 1.3. Vital signs (Heart rate, Blood pressure) at Study day 1: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose; Study day 15: baseline + 10 hours and 24 hours; Study day 29: baseline + 10 hours and 24 hours; Study day 37 follow up visit, once 1.4. Numeric Rating Scale (NRS) pain score at Study day 1: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose 2. Dermal imaging/scoring 2.1. Perfusion by Laser Speckle Contrast Imaging (LSCI) at Study day 1: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose; Study day 15: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose; Study day 29: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose 2.2. Erythema by Antera 3D camera at Study day 1: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose; Study day 15: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose; Study day 29: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose 2.3. Erythema grading score: Clinical Erythema Assessment (CEA) at Study day 1: baseline + 10 hours and 24 hours post dose; Study day 15: baseline + 10 hours and 24 hours post dose; Study day 29: baseline + 10 hours and 24 hours post dose 3. Blister exudate analysis 3.1. Neutrophils and monocyte subsets at Study day 1: 10 hours and 24 hours post dose; Study day 15: 10 hours and 24 hours post dose; Study day 29: 10 hours and 24 hours post dose | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Blister exudate analysis 1.1. Other immune cell subsets (lymphocytes etc) 1.2. Cytokines and/or chemokines, such as CCL2 at Study day 1: 10 hours and 24 hours post dose; Study day 15: 10 hours and 24 hours post dose; Study day 29: 10 hours and 24 hours post dose 2. Blood analysis 2.1. Serum and plasma biomarkers (e.g. cytokines and/or chemokines) at Study day 1: baseline + 2 hours, 4 hours, 10 hours and 24 hours post dose; Study day 15: baseline + 10 hours and 24 hours; Study day 29: baseline + 10 hours and 24 hours; Study day 37 follow up visit, once | — |
Countries
Netherlands
Outcome results
None listed