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

NCT ID: NCT01522794

Last Updated: 2014-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2012-04-30

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.

Conditions

Anemia of Chronic Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NOX-H94

Single dose of NOX-H94

Group Type: EXPERIMENTAL

NOX-H94

Intervention Type: DRUG

single i.v. infusion

Placebo

Single dose of placebo control

Group Type: PLACEBO_COMPARATOR

Placebo solution

Intervention Type: DRUG

single i.v. infusion

Interventions

NOX-H94

single i.v. infusion

Intervention Type: DRUG

Placebo solution

single i.v. infusion

Intervention Type: DRUG

Other Intervention Names

lexaptepid pegol

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

TME Pharma AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kai Riecke, MD

Role: STUDY_DIRECTOR

TME Pharma AG

Peter Pickkers, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 25163699 (View on PubMed)

Related Links

https://ash.confex.com/ash/2012/webprogram/Paper50672.html

Result summary: Abstract 3452, ASH 2012

Other Identifiers

2011-005022-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SNOXH94C101

Identifier Type: -

Identifier Source: org_study_id