First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NOX-H94

Overview

This is the first clinical trial with NOX-H94. The purpose of this clinical trial is to identify a safe and efficacious treatment regimen for the clinical development of NOX-H94 in patients with anemia of chronic disease (inflammation).

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Factorial Assignment
  • Primary Purpose: Treatment
  • Masking: Double (Participant, Investigator)
• Study Primary Completion Date: March 2012

Detailed Description

NOX H94 is a pegylated Spiegelmer that specifically binds to human hepcidin, thereby antagonizing its role in hemostasis, and is therefore indicated for use in anemia of inflammation. Human hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. Hepcidin expression in hepatocytes is regulated by multiple, in particular opposing signals, including systemic iron availability, hepatic iron stores, erythropoietic activity, hypoxia, and inflammatory states. These different signals are integrated transcriptionally. In chronic inflammation, such as occurs in rheumatoid arthritis, chronic kidney disease or cancer, elevated hepcidin levels have been measured and may be a key factor leading to anemia in these patients. NOX-H94 is therefore indicated for treatment of patients with an anemia of inflammation, which is characterized by increased intracellular iron stores, increased serum ferritin concentrations and reduced sensitivity to treatment with erythropoiesis stimulating agents (ESAs), due to the limited availability of serum iron. Antagonism of hepcidin by NOX-H94 therefore leads to elevated levels of iron and transferrin saturation in the peripheral blood and could supply iron for erythropoiesis thereby correcting the anemia.

Interventions

• Drug: NOX-H94
  • Dosage form: NOX-H94 25 mg (oligonucleotide basis) Solution for Injection Strength: 14.6 mg NOX-H94 / mL Dose: 0.3 – 4.8 mg/kg single dose Route: IV infusion over 15 minutes / SC administration
• Other: Glucose 5%
  • Placebo

Arms, Groups and Cohorts

• Experimental: NOX-H94
  • Group A: single 15 minutes IV infusion of 0.3 mg/kg NOX-H94 Group B: single 15 minutes IV infusion of 0.6 mg/kg NOX-H94 Group C: single 15 minutes IV infusion of 1.2 mg/kg NOX-H94 Group D: single 15 minutes IV infusion of 2.4 mg/kg NOX-H94 Group E: single 15 minutes IV infusion of 4.8 mg/kg NOX-H94 Group F: single / repeated SC injection of NOX-H94 over a treatment period of 2 weeks Group G: multiple doses of NOX-H94 as a 15 minutes IV infusion over a treatment period of 2 weeks Group H: multiple doses of NOX-H94 as a 15 minutes IV infusion over a treatment period of 2 weeks
• Placebo Comparator: Glucose 5%
  • Group A to Group H get NOX-H94 or Placebo

Clinical Trial Outcome Measures

Primary Measures

• Incidence of adverse events
  • Time Frame: 0 to 90 days

Secondary Measures

• drug plasma concentrations
  • Time Frame: 0 to 29 days

Participating in This Clinical Trial

Inclusion Criteria

• Male subjects or female subjects of non-childbearing potential (Groups A to E), male subjects (groups F to H) – Age 18-65 years – Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory parameters – Males willing to use 2 means of contraceptive methods for at least 2 months after the final examination Exclusion Criteria:

1. Anemia predominantly caused by other factors than chronic disease. 2. Iron overload or disturbances in utilization of iron. 3. Intravenous iron treatment or blood transfusion within 4 weeks prior to screening visit. 4. Erythropoietin treatment within 4 weeks prior to screening visit. 5. Intake of Intravenous iron, Blood transfusions, Erythropoietin during their trial participation. 6. Resting supine pulse rate < 40 or > 100 beats / min. 7. Resting supine blood pressure: Systolic blood pressure < 90 or > 160 mmHg Diastolic blood pressure < 40 or > 100 mmHg. 8. History or presence of confirmed orthostatic hypotension defined. 9. Positive test of HIV type 1/2 antibodies, HBs antigen, HBc antibodies, HCV antibodies. 10. Participation in another clinical trial during the last 3 months before starting this trial. 11. Positive test for drugs of abuse. 12. Diseases or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. 13. Marked repolarization abnormality. 14. Current bronchial asthma, childhood asthma which has been resolved is allowed. 15. Definite or suspected history of drug allergy or hypersensitivity or intolerance to PEG 16. Regular intake of over 14 units of alcohol per week for women and 21 units for men. 17. Not able to abstain from consumption of:

• Caffeine containing beverages or food (tea, coffee, cola, chocolate, etc.) – Quinine containing beverages or food (bitter lemon, tonic water) – Grapefruit juice (sweet or sour) – Poppy seeds containing beverages or food 18. Subjects who have donated any blood, plasma or platelets in the month prior to screening 19. History of seizures or at risk 20. Known or suspected of not being able to comply with the trial protocol and/or clinical unit restrictions. 21. History of or presence of clinically significant diseases other than the underlying disease. 22. Surgery or trauma with significant blood loss within the last 2 months before administration of study drug. 28. History of increased bleeding risk.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • TME Pharma AG
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Riecke Kai, MD, Study Director, TME Pharma AG