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

Primary Purpose

Anemia, Chronic Diseases, Inflammation

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
NOX-H94
Glucose 5%
Sponsored by
TME Pharma AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia focused on measuring NOX-H94, Hepcidin, Anemia, Inflammation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • HMR

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

NOX-H94

Glucose 5%

Arm Description

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

Group A to Group H get NOX-H94 or Placebo

Outcomes

Primary Outcome Measures

Incidence of adverse events

Secondary Outcome Measures

drug plasma concentrations

Full Information

First Posted
June 8, 2011
Last Updated
January 22, 2016
Sponsor
TME Pharma AG
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1. Study Identification

Unique Protocol Identification Number
NCT01372137
Brief Title
First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NOX-H94
Official Title
First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NOX-H94
Study Type
Interventional

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TME Pharma AG

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Chronic Diseases, Inflammation
Keywords
NOX-H94, Hepcidin, Anemia, Inflammation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NOX-H94
Arm Type
Experimental
Arm Description
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
Arm Title
Glucose 5%
Arm Type
Placebo Comparator
Arm Description
Group A to Group H get NOX-H94 or Placebo
Intervention Type
Drug
Intervention Name(s)
NOX-H94
Other Intervention Name(s)
lexaptepid pegol
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Glucose 5%
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Incidence of adverse events
Time Frame
0 to 90 days
Secondary Outcome Measure Information:
Title
drug plasma concentrations
Time Frame
0 to 29 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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: Anemia predominantly caused by other factors than chronic disease. Iron overload or disturbances in utilization of iron. Intravenous iron treatment or blood transfusion within 4 weeks prior to screening visit. Erythropoietin treatment within 4 weeks prior to screening visit. Intake of Intravenous iron, Blood transfusions, Erythropoietin during their trial participation. Resting supine pulse rate < 40 or > 100 beats / min. Resting supine blood pressure: Systolic blood pressure < 90 or > 160 mmHg Diastolic blood pressure < 40 or > 100 mmHg. History or presence of confirmed orthostatic hypotension defined. Positive test of HIV type 1/2 antibodies, HBs antigen, HBc antibodies, HCV antibodies. Participation in another clinical trial during the last 3 months before starting this trial. Positive test for drugs of abuse. Diseases or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. Marked repolarization abnormality. Current bronchial asthma, childhood asthma which has been resolved is allowed. Definite or suspected history of drug allergy or hypersensitivity or intolerance to PEG Regular intake of over 14 units of alcohol per week for women and 21 units for men. 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 Subjects who have donated any blood, plasma or platelets in the month prior to screening History of seizures or at risk Known or suspected of not being able to comply with the trial protocol and/or clinical unit restrictions. History of or presence of clinically significant diseases other than the underlying disease. Surgery or trauma with significant blood loss within the last 2 months before administration of study drug. 28. History of increased bleeding risk.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Riecke Kai, MD
Organizational Affiliation
TME Pharma AG
Official's Role
Study Director
Facility Information:
Facility Name
HMR
City
London
ZIP/Postal Code
NW10 7EW
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
30957581
Citation
Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.
Results Reference
derived

Learn more about this trial

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

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