Anemia of Chronic Disease Clinical Trial
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
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.
Status | Completed |
Enrollment | 24 |
Est. completion date | April 2012 |
Est. primary completion date | March 2012 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 18 Years to 35 Years |
Eligibility |
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 ?-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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Netherlands | Radboud University Nijmegen Medical Centre | Nijmegen |
Lead Sponsor | Collaborator |
---|---|
NOXXON Pharma AG |
Netherlands,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | serum iron | Change versus baseline; comparison of subjects treated with NOX-H94 versus placebo | 9 hours | No |
Secondary | Pharmacodynamics: Effects of NOX-H94 on Iron homeostasis | Change from baseline and group comparison (NOX-H94 vs. placebo) of: serum iron, transferrin saturation, ferritin |
up to 2 Weeks | No |
Secondary | Pharmacokinetic profile of NOX-H94 | plasma concentration-time profile T0 to 2 weeks | 12 time points over 2 Weeks | No |
Secondary | Safety and tolerability | Safety and tolerability parameters will be evaluated along the entire study duration consisting of spontaneously reported adverse events, physical examination and vital signs, hematology and clinical chemistry laboratory examinations. | up to 2 Weeks | Yes |
Secondary | Effects of NOX-H94 on innate immune response | To assess the effect of a single dose administration of NOX H94 on the innate immune response during experimental endotoxemia: TNF-a, IL-6, IL-1RA, IL-10 | up to 2 weeks | No |
Secondary | Pharmacokinetics: Cmax of NOX-H94 | Day 1 | No | |
Secondary | Pharmacokinetics: AUC of NOX-H94 | 0-2 weeks | No | |
Secondary | Pharmacokinetics: Clearance of NOX-H94 | 0-2 weeks | No | |
Secondary | Pharmacodynamics: effect of NOX-H94 on Red blood cell parameters | Change versus baseline and group comparison: reticulocyte hemoglobin content, hemoglobin, mean cell volume, mean cell hemoglobin | 0- 2 weeks | No |
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