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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%

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:

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.

Sites / Locations

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

NCT ID

NCT01372137

First Posted

June 8, 2011

Last Updated

January 22, 2016

Sponsor

TME Pharma AG

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

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

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

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

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

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