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

TME Pharma

Status and phase: Completed; Phase 1

Conditions: Anemia of Chronic Disease

Treatments: Drug: Placebo solution; Drug: NOX-H94

Study type: Interventional

Funder types: Industry

Identifiers

NCT01522794

2011-005022-22 (EudraCT Number)

SNOXH94C101

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: Male

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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24 participants in 2 patient groups, including a placebo group

NOX-H94

Experimental group

Description:

Single dose of NOX-H94

Treatment:

Drug: NOX-H94

Placebo

Placebo Comparator group

Description:

Single dose of placebo control

Treatment:

Drug: Placebo solution