Adrecizumab-LPS Study

• Register: ClinicalTrials.gov
• Last refreshed on: 8 February 2021
• Main ID: NCT03083171
• Date of registration: 13/03/2017
• Prospective Registration: No
• Primary sponsor: Adrenomed AG
• Public title: Adrecizumab-LPS Study
• Scientific title: A Randomized Double-blind Placebo-controlled Phase I Study on the Safety, Tolerability and Pharmacokinetics/-Dynamics of Escalating Single Intravenous Doses of ADRECIZUMAB (HAM8101) in Healthy Male Subjects During Experimental Endotoxemia.
• Date of first enrolment: January 4, 2017
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03083171
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

Netherlands

Contacts

• Name: Peter Pickkers, MD, PhD
• Affiliation: Radboud University

Key inclusion & exclusion 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:

1. Unwillingness to abstain from any medication, including recreational drugs 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, within 1 day prior to the treatment
day and 1 day after the treatment day.

3. Previous participation in a trial where LPS was administered.

4. Surgery or trauma with significant blood loss or blood donation within 3 months prior
to the treatment day.

5. 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 mmHg)

- Hypotension (RR systolic <100 or RR diastolic <50 mmHg)

- Conduction abnormalities on the ECG consisting of a 1st degree atrioventricular
block or a complex bundle branch block

- Any chronic cardiac arrhythmias (except PAC's, PVC's)

6. Renal impairment: plasma creatinine >120 µmol/L

7. Liver function tests (alkaline phosphatase, AST, ALT and/or ?-GT) above 2x the upper
limit of normal.

8. History of asthma

9. Atopic constitution

10. CRP above 2x the upper limit of normal, or clinically significant acute illness,
including infections, within 2 weeks prior to the treatment day.

11. Treatment with investigational drugs or participation in any other clinical trial
within 30 days prior to the treatment day.

12. Known or suspected of not being able to comply with the trial protocol.

13. Known hypersensitivity to any excipients of the drug formulations used.

14. Inability to personally provide written informed consent (e.g. for linguistic or
mental reasons) and/or take part in the study.



Age minimum: 18 Years
Age maximum: 35 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Healthy Volunteers

Intervention(s)

Drug: Endotoxin

Drug: Placebo

Drug: Adrecizumab

Primary Outcome(s)

Safety and tolerability expressed in total number of treatment related (serious) adverse events. [Time Frame: 3 months follow-up period]

Secondary Outcome(s)

Plasma levels of adrenomedullin and MR-proadrenomedullin [Time Frame: T=0 hours, T=1 hours, T=1.25 hours, T=1.5 hours, T=2 hours, T=2.5 hours T=3 hours, T=4 hours, T=5 hours, T=9 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after LPS administration]

Terminal t1/2 of free Adrecizumab (pharmacokinetics) [Time Frame: T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration]

Area under the curve (AUC) of free Adrecizumab (pharmacokinetics) [Time Frame: T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration]

Cytokines [Time Frame: T=0 hours, T=1 hours, T=1.5 hours, T=2 hours, T=2.5 hours T=3 hours, T=4 hours, T=5 hours, T=6 hours, T=9 hours after LPS administration]

Kidney damage markers [Time Frame: Baseline, T=0 to T=3 hours, T=3 to T=6 hours, T=6 to T=9 hours, T=9 to T=12 hours, T=12 to T=24 hours after LPS administration]

Clearance of free Adrecizumab (pharmacokinetics) [Time Frame: T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration]

Peak plasma concentration (Cmax) of free Adrecizumab (pharmacokinetics) [Time Frame: T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration]

Volume of distribution of free Adrecizumab (pharmacokinetics) [Time Frame: T=0 hours, T=0.25 hours, T=0.5 hours, T=1 hours, T=1.5 hours, T=2 hours, T=3 hours, T=4 hours, T=8 hours, T=24 hours, T=7 days, T=14 days, T=28 days, T=60 days, T=90 days after Adrecizumab administration]

Secondary ID(s)

Adrecizumab-LPS

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Radboud University