Pharmacokinetics/Pharmacodynamics of NOX-H94 in the Human Endotoxemia Model

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01522794
• Other study ID #: SNOXH94C101
• Secondary ID: 2011-005022-22
• Status: Completed
• Phase: Phase 1
• First received: January 18, 2012
• Last updated: November 7, 2014
• Start date: January 2012
• Est. completion date: April 2012

Study information

• Verified date: November 2014
• Source: NOXXON Pharma AG
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia of Chronic Disease
• Chronic Disease
• Endotoxemia

Intervention

Drug:
• NOX-H94
single i.v. infusion
• Placebo solution
single i.v. infusion

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
NOXXON Pharma AG

Country where clinical trial is conducted

Netherlands, 

Outcome

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

External Links

•   Literature: Kemna et. al. 2005
•   Publication of clinical trial (open access)
•   Result summary: Abstract 3452, ASH 2012