Sepsis severe bacterial infection.
Conditions
Interventions
Single escalating doses of ADRECIZUMAB, administered as intravenous (i.v.)
infusion in 3 treatment groups with sequential higher doses (0.5 mg/kg, 2mg/kg
and 8mg/kg) and 1 treatment group with place
Sponsors
Adrenomed AG
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Written informed consent to participate in this trial prior to any study mandated procedure. 2. Male subjects aged 18 to 35 years, inclusive. 3. Subjects have to agree to use a reliable way of contraception with their partners from study entry until 3 months after study drug administration. 4. BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg and a upper limit of 100 kg. 5. Healthy as determined by medical history, physical examination, vital signs, 12 lead electrocardiogram, and clinical laboratory parameters
Exclusion criteria
Exclusion criteria: 1. Unwillingness to abstain from any medication, recreational drugs, anti-oxidant or vitamin supplements during the course of the study and within 7 days prior to the treatment day. 2. Unwillingness to abstain from smoking or alcohol 1 day prior to the treatment day and during the first 24 hours of the study. 3. Surgery or trauma with significant blood loss or blood donation within 3 months prior to the treatment day. 4. History, signs or symptoms of cardiovascular disease, in particular: * History of frequent vasovagal collapse or of orthostatic hypotension * Resting pulse rate *45 or *100 beats / min * Hypertension (RR systolic >160 or RR diastolic >90) * Hypotension (RR systolic 120 µmol/L 6. Liver function tests (alkaline phosphatase, AST, ALT and/or *-GT) above 2x the upper limit of normal. 7. History of asthma 8. Atopic constitution 9. CRP above 2x the upper limit of normal or clinically significant acute illness, including infections, within 2 weeks before administration of the study drug. 10. Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to study drug administration. 11. Known or suspected of not being able to comply with the trial protocol. 12. Known hypersensitivity to any excipients of the drug formulations used. 13. Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events Vital signs during the first 8 hours after administration of ADRECIZUMAB: - Heart rate (continuously by ECG leads) - Blood pressure (continuously by intra-arterial line) - Oxygen saturation (continuously by pulse-oximetry) - Temperature (measured intermittently in the ear by infrared thermometer) Local tolerability at site of i.v. infusion Safety laboratory parameters: - Hb, Ht, leucocytes, thrombocytes, leucocyte differential blood count, sodium, potassium, creatinine, urea, alkaline phosphatase, ALT, AST, *GT, CK, PCT, CRP. -12-lead electrocardiogram (ECG), at baseline, within 1 hour after ADRECIZUMAB administration, and at 7 to 8 hrs after ADRECIZUMAB administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Pharmacokinetics of ADRECIZUMAB: AUC, Cmax, terminal t1/2, Cl, V. * Blood plasma levels of adrenomedullin * Ex vivo cytokine production (whole blood will be stimulated with LPS after which cytokine production will be determined by ELISA). | — |
Countries
Netherlands
Outcome results
None listed