Clinical trial NCT01522794: Pharmacokinetics/Pharmacodynamics of NOX-H94 in the Human Endotoxemia Model
Official title: Randomized Double Blind Placebo Controlled PK/PD Study on the Effects of a Single Intravenous Dose of NOX-H94 on Serum Iron During Experimental Human Endotoxemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anemia of Chronic Disease
Lead sponsor: TME Pharma AG
Sponsor class: INDUSTRY
First posted: 2012-02-01
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of the anti-hepcidin Spiegelmer NOX-H94 on iron homeostasis during systemic inflammation induced by endotoxin.

In the human endotoxemia model, intravenously administered lipopolysaccharide elicits an inflammatory response with release of pro-inflammatory cytokines, such as IL-6 and TNF-alfa, with subsequent induction of hepcidin. As a consequence of hepcidin induction, serum iron concentrations decrease.

This study in healthy subjects investigates the capacity of NOX-H94 to inactivate hepcidin and to prevent serum iron decrease in a pathophysiological model prior to studying the efficacy of NOX-H94 in patients with anemia of chronic disease.


Eligibility criteria: Main Inclusion Criteria:

* BMI between 18 and 30 kg/m², with a lower limit of body weight of 50 kg
* Healthy as determined by medical history, physical examination, vital signs, 12 lead electrocardiogram, and clinical laboratory parameters
* Serum iron and red blood parameters Hb, MCV, ferritin, serum iron, and total iron binding capacity within reference range

Main Exclusion Criteria:

* Use of any medication, recreational drugs or anti-oxidant vitamin supplements within 7 days
* Use of caffeine, nicotine, or alcohol within 1 day
* Previous participation in a trial where LPS was administered
* Surgery or trauma with significant blood loss or blood donation within 3 months
* History, signs or symptoms of cardiovascular disease (vaso-vagal collapse or of orthostatic hypotension, Resting pulse rate ≤45 or ≥100/min, Hypertension, Hypotension, ECG conduction abnormalities)
* Renal impairment: plasma creatinine \>120 µmol/L
* Liver function tests (alkaline phosphatase, AST, ALT and γ-GT) outside of the reference range or total bilirubin \>20 µmol/L
* Hemoglobin or iron parameters (iron, transferring saturation, ferritin) outside of the reference ranges
* History of asthma
* Immuno-deficiency
* Positive test of HIV type 1/2 antibodies, HBs antigen, HBc antibodies and HCV antibodies unless antibody titer is induced by vaccination
* CRP \> reference range or clinically significant acute illness, including infections, within 2 weeks
* Treatment with investigational drugs or participation in any other clinical trial within 30 days prior to study drug administration
* Known or suspected of not being able to comply with the trial protocol
* Inability to personally provide written informed consent and/or take part in the study

Primary outcomes:
measure: serum iron
timeFrame: 9 hours
Secondary outcomes:
measure: Pharmacodynamics: Effects of NOX-H94 on Iron homeostasis
timeFrame: up to 2 Weeks
measure: Pharmacokinetic profile of NOX-H94
timeFrame: 12 time points over 2 Weeks
measure: Safety and tolerability
timeFrame: up to 2 Weeks
measure: Effects of NOX-H94 on innate immune response
timeFrame: up to 2 weeks
measure: Pharmacokinetics: Cmax of NOX-H94
timeFrame: Day 1
measure: Pharmacokinetics: AUC of NOX-H94
timeFrame: 0-2 weeks
measure: Pharmacokinetics: Clearance of NOX-H94
timeFrame: 0-2 weeks
measure: Pharmacodynamics: effect of NOX-H94 on Red blood cell parameters
timeFrame: 0- 2 weeks
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: TME Pharma AG
name: Kai Riecke, MD
role: STUDY_DIRECTOR
affiliation: Radboud University Medical Center
name: Peter Pickkers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Eijk LT, John AS, Schwoebel F, Summo L, Vauleon S, Zollner S, Laarakkers CM, Kox M, van der Hoeven JG, Swinkels DW, Riecke K, Pickkers P. Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans. Blood. 2014 Oct 23;124(17):2643-6. doi: 10.1182/blood-2014-03-559484. Epub 2014 Aug 27.