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

Primary Purpose

Anemia of Chronic Disease

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

NOX-H94

Placebo solution

About this trial

This is an interventional treatment trial for Anemia of Chronic Disease

Eligibility Criteria

18 Years - 35 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

Radboud University Nijmegen Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

NOX-H94

Placebo

Arm Description

Single dose of NOX-H94

Single dose of placebo control

Outcomes

Primary Outcome Measures

serum iron

Change versus baseline; comparison of subjects treated with NOX-H94 versus placebo

Secondary Outcome Measures

Pharmacodynamics: Effects of NOX-H94 on Iron homeostasis

Change from baseline and group comparison (NOX-H94 vs. placebo) of: serum iron, transferrin saturation, ferritin

Pharmacokinetic profile of NOX-H94

plasma concentration-time profile T0 to 2 weeks

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.

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-α, IL-6, IL-1RA, IL-10

Pharmacokinetics: Cmax of NOX-H94

Pharmacokinetics: AUC of NOX-H94

Pharmacokinetics: Clearance of NOX-H94

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

Full Information

NCT ID

NCT01522794

First Posted

January 18, 2012

Last Updated

November 7, 2014

Sponsor

TME Pharma AG

1. Study Identification

Unique Protocol Identification Number

NCT01522794

Brief Title

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

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Completed

Study Start Date

January 2012 (undefined)

Primary Completion Date

March 2012 (Actual)

Study Completion Date

April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

TME Pharma AG

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anemia of Chronic Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NOX-H94

Arm Type

Experimental

Arm Description

Single dose of NOX-H94

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Single dose of placebo control

Intervention Type

Drug

Intervention Name(s)

NOX-H94

Other Intervention Name(s)

lexaptepid pegol

Intervention Description

single i.v. infusion

Intervention Type

Drug

Intervention Name(s)

Placebo solution

Intervention Description

single i.v. infusion

Primary Outcome Measure Information:

Title

serum iron

Description

Change versus baseline; comparison of subjects treated with NOX-H94 versus placebo

Time Frame

9 hours

Secondary Outcome Measure Information:

Title

Pharmacodynamics: Effects of NOX-H94 on Iron homeostasis

Description

Change from baseline and group comparison (NOX-H94 vs. placebo) of: serum iron, transferrin saturation, ferritin

Time Frame

up to 2 Weeks

Title

Pharmacokinetic profile of NOX-H94

Description

plasma concentration-time profile T0 to 2 weeks

Time Frame

12 time points over 2 Weeks

Title

Safety and tolerability

Description

Time Frame

up to 2 Weeks

Title

Effects of NOX-H94 on innate immune response

Description

To assess the effect of a single dose administration of NOX H94 on the innate immune response during experimental endotoxemia: TNF-α, IL-6, IL-1RA, IL-10

Time Frame

up to 2 weeks

Title

Pharmacokinetics: Cmax of NOX-H94

Time Frame

Day 1

Title

Pharmacokinetics: AUC of NOX-H94

Time Frame

0-2 weeks

Title

Pharmacokinetics: Clearance of NOX-H94

Time Frame

0-2 weeks

Title

Pharmacodynamics: effect of NOX-H94 on Red blood cell parameters

Description

Change versus baseline and group comparison: reticulocyte hemoglobin content, hemoglobin, mean cell volume, mean cell hemoglobin

Time Frame

0- 2 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kai Riecke, MD

Organizational Affiliation

TME Pharma AG

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Peter Pickkers, MD, PhD

Organizational Affiliation

Radboud University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Radboud University Nijmegen Medical Centre

City

Nijmegen

ZIP/Postal Code

6500 HB

Country

Netherlands

12. IPD Sharing Statement

Citations:

PubMed Identifier

25163699

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.

Results Reference

derived

Links:

URL

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

Description

Result summary: Abstract 3452, ASH 2012

URL

http://dx.doi.org/10.1182/blood-2014-03-559484

Description

Publication of clinical trial (open access)

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

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