Oncology autoimmune disorders cancer inflammatory disorders
Conditions
Interventions
None listed
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male participants between 18 and 35 years of age (inclusive), at the time of signing the informed consent. 2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG. 3. A body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive), and a minimum body weight of 50 kg. 4. Able to give written informed consent and willing to comply with all study-related procedures.
Exclusion criteria
Exclusion criteria: 1. Clinically significant abnormalities, as judged by the investigator, in test results (including physical examination, laboratory tests, ECG and vital signs). 2. History of medical conditions, which in the opinion of the investigator may compromise participant*s safety or scientific value of the study, posing an unacceptable risk to the participant or interfere with the participant's ability to comply with study procedures or abide by study restrictions. 3. History of trauma with likely damage to the spleen or surgery to spleen, or history of hip fracture or surgery in the pelvic area. 4. Previous participation in a systemic (i.v./inhaled) LPS challenge trial within a year before the first study day. 5. Any active inflammatory or infectious disease (e.g., periodontitis), with the exception of common viral or fungal skin infections such as plantar warts or athlete*s foot. 6. Febrile illness within 30 days before the start of the first study day. 7. Antibiotic use, operation or intervention by surgeon/dentist within one month before the first study day. 8. Hemorrhagic diathesis (easy bruising, epistaxis, gastro-intestinal bleeding, history of serious bleeding). 9. Clinically significant hypertension (defined as systolic blood pressure > 145 mmHg or diastolic blood pressure > 90 mmHg, repeatedly measured after 5 minutes in resting supine position), or clinically significant hypotension (defined as systolic blood pressure 120ms, PR interval > 210ms, QTcF interval > 470ms). 11. Positive test results for hepatitis B, hepatitis C, HIV antibody or any other obvious disease associated with immune deficiency. 12. 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. 13. 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). 14. Loss or donation of blood over 500 mL within 3 months prior to screening or donation of plasma within 14 days prior to screening. 15. Participation in an investigational drug or device study within 3 months between last dosing in previous study and admission to the CRU in present study or more than 4 times in the past year. 16. Any vaccination within the last 3 months; COVID-19 vaccination (or infection as confirmed by a PCR test) is allowed up until 4 weeks prior to admission to the CRU; COVID-19 booster vaccination is allowed up until 2 weeks prior to admission to the CRU.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Whole-blood samples o Leucocyte differential o Flow cytometry (neutrophils, monocyte subsets, T cells, B cells, NK cells and dendritic cells, activation and proliferation markers) o Cytokine analysis (including, but not limited to TNF, IL-1β, IL-6 and IL-8) • Bone-marrow aspiration and biopsy o Flow cytometry (i.e., neutrophils, monocyte subsets, T cells, B cells, NK cells, dendritic cells, myelocyte and lymphocyte progenitor cells, myeloid-derived suppressor cells, bone-marrow derived dendritic cells, activation and proliferation markers) o Cytomorphology (i.e., overall cell count, megakaryopoiesis, erythropoiesis, leukopoiesis - myelo- and lymphopoiesis) o Immunohistology of the bone marrow biopsy • RNA-sequencing of whole blood and blood marrow samples to capture the (immune) cells expression profile • Feasibility o Questionnaire to identify experiences of healthy volunteers after bone marrow sampling o Demographics, age and employment status will be collected o Pain visual analogue scale (VAS) • Safety and tolerability o Adverse events ((S)AEs) throughout the study at every study visit (rate, duration and severity) o Concomitant medication throughout the study at every study visit o Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic blood pressure (mmHg)), Respiratory rate as per assessment schedule o Clinical laboratory tests (Hematology, blood chemistry and urinalysis) as per assessment schedule o ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF) as per assessment schedule | — |
Secondary
| Measure | Time frame |
|---|---|
| N.a. | — |
Countries
Netherlands
Outcome results
None listed