inflammatory challenge study
Conditions
Interventions
POLB 001 or matching placebo will be administered orally, twice daily, for 7
consecutive days.
Sponsors
ORPH Pharma IP Company Limited
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male volunteers aged 18 to 55 years, inclusive. Health 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, coagulation, and urinalysis. In the case of uncertain or questionable results, tests performed during screening may be repeated to confirm eligibility or judged by the investigator to be clinically irrelevant for healthy subjects. 2. BMI in the range of 18 to 32 kg/m2, a minimum body weight of 50 kg. 3. Fitzpatrick skin type I-III. 4. Able to give written informed consent and willing to comply with all study-related procedures. 5. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. (A history of) any clinically significant medical condition or abnormalities, as judged by the investigator. 2. History of sepsis, cardiovascular disease or malignancy. 3. History of trauma with likely damage to the spleen or surgery to spleen. 4. History of alcohol or drug abuse. 5. Any clinically significant febrile illness 30 days preceding study Day 1. 6. History of serious bleeding. 7. Clinical evidence of significant or unstable medical illness including neurological, hematological, cardiovascular (including clinically significant arrhythmia), hepatic, pulmonary, metabolic, gastrointestinal, renal, psychiatric, endocrine, or infectious diseases or malignancies. Subjects who have had splenectomy. 8. Previous participation in a systemic (i.v./inhaled) LPS challenge trial within a year before the first study day. 9. Have any current and / or recurrent pathologically, clinically significant skin condition at the lower forearms (i.e., atopic dermatitis) including tattoos. 10. Antibiotic use, operation or intervention by surgeon/dentist within one month before the first study day. 11. Subjects who have used any prescribed or non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the first dose administration, or less than 5 half-lives (whichever is longer), and during the study (except for vitamin/mineral supplements) unless, in the opinion of the Investigator, the medication will not interfere with the study procedures or compromise safety. 12. Subjects who have received any medications, including St John*s Wort, known to chronically alter drug absorption or elimination processes within 30 days of the first dose administration unless, in the opinion of the Investigator, the medication will not interfere with the study procedures or compromise safety. 13. Any active inflammatory or infectious disease (e.g., periodontitis). 14. Known immunodeficiency. 15. Positive test results for Hepatitis B, Hepatitis C, HIV antibody. 16. Subjects who consume on average more than 3 units of alcohol per day (one alcohol unit =1 beer [12 oz] =1 wine [5 oz] =1 spirits [1.5 oz]) or are unable to abstain from using alcohol during the study. 17. Subjects with a positive urine drug screen/alcohol test result at screening or first admission or a history of substance abuse in the last 12 months prior to the start of the study. 18. Subjects who smoke more than 6 cigarettes or the equivalent in tobacco per day and are unwilling to abstain from smoking during the study period (from screening until EOS). 19. Loss or donation of blood over 500 mL within 3 months prior to screening or donation of plasma within 14 days prior to screening. 20. Participation in an investigational drug or device study within 3 months, or 5 half-lives whichever is longer, between last dosing in previous study and first dosing in present study or more than 4 times in the past year. 21. Any vaccination within the last 3 months; COVID19 vaccination (or time of infection) is allowed up until 2 weeks prior to the first POLB 001 /placebo dosing. 22. Intention to receive any vaccination(s) before the last day of follow-up (with the exception of vaccinations recommended for COVID19 as defined by government vaccination guidelines).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Skin response by imaging o Perfusion by laser speckle contrast imaging o Erythema by multispectral imaging o Clinical score • Blister exudate analysis o Flow cytometry (neutrophils, monocyte subsets, T cells, B cells, NK cells and dendritic cells) o Cytokines (IL-6, IL-8, TNF, IL-1β) • Skin punch biopsy (3 mm) o Explorative analysis of MK2, HSP-27 and p38 MAPK expression by qPCR) • Safety and tolerability o Vital signs (HR, temperature) o Treatment-Emergent Adverse Events o Electrocardiography o Haematology and chemistry blood panels • Blood o Cytokines (IL-6, IL-8, IL-10, TNF, IL-1β) o Leucocyte differential o Vascular markers (VCAM, ICAM, P-selectin, E-selectin, by 4-plex MSD) o CRP o P38 MAPK phosphorylation levels • Safety and tolerability o Vital signs (HR, temperature) o Treatment-Emergent Adverse Events o Electrocardiography o Haematology and chemistry blood panels PK serum concentration analysis of POLB 001 Ex vivo LPS response (baseline versus pre-IV LPS challenge; IL-6 and TNF) | — |
Secondary
| Measure | Time frame |
|---|---|
| N.a. | — |
Countries
Netherlands
Outcome results
None listed