E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Erythropoiesis stimulating agents (ESA) hyporesponsive anaemia in renal dialysis patients |
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E.1.1.1 | Medical condition in easily understood language |
Anaemia in renal dialysis patients that does not respond to agents (ESA) that stimulate red cell production |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10038359 |
E.1.2 | Term | Renal and urinary disorders |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10005329 |
E.1.2 | Term | Blood and lymphatic system disorders |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058123 |
E.1.2 | Term | Renal anaemia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of single and repeated doses of NOX-H94 in dialysis patients |
Beurteilung der Sicherheit und Verträglichkeit nach einmaliger Gabe und bei wiederholter Verabreichung von NOX-H94 bei Dialysepatienten |
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E.2.2 | Secondary objectives of the trial |
• To study the PK with a focus on plasma accumulation and elimination, the PD, and the efficacy of NOX-H94 in dialysis patients with functional iron deficiency
• To obtain first data on efficacy of NOX-H94 with regard to the response of Hb
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• Untersuchung der PK mit besonderem Augenmerk auf Wirkstoffkumulation im Plasma und Elimination, der PD sowie der Wirksamkeit von NOX-H94 bei Dialysepatienten mit funktionellem Eisenmangel
• Erhebung erster Daten zur Wirksamkeit von NOX-H94 im Hinblick auf das Ansprechen der Hb-Konzentration |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent
2. Male or female of non-childbearing potential
3. Age 18 to 85 years
4. End stage renal disease treated with maintenance haemodialysis since ≥3 months, 3 times weekly
5. Anaemia : Hb 7 to 11 g/dL
6. Functional iron deficiency: Transferrin saturation <30%,
Ferritin ≥300 ng/mL.
7. ESA hyporesponsiveness with erythropoietin dose ≥12,000 IU/ week stable for ≥4 weeks
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E.4 | Principal exclusion criteria |
1. Inability to personally provide written informed consent or to under-stand and collaborate throughout the study.
2. Inability or unwillingness to comply with study restrictions.
3. Participation in any clinical research study evaluating an investigational drug or therapy within 30 days from screening visit or prior enrolment in this study.
4. Pregnancy or lactation.
5. Treatment with darbepoetin or methoxy-polyethylenglycol-epoetin
6. Uncontrolled cardiovascular disease, unstable peripheral arterial or cerebrovascular disease, uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg).
7. Congestive heart failure: New York Heart Association Class III or IV.
8. Unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty/stents, or coronary artery bypass grafting <3 months prior screening.
9. Any other medical conditions requiring a change in treatment within 4 weeks prior to screening or making study participation unadvisable (at the discretion of the investigator).
10. History of clinically relevant haemolysis and/or blood loss.
11. AST, ALT, or bilirubin ≥2.0 times the upper limit of normal.
12. Known bone marrow fibrosis.
13. Treatment with i.v. iron <4 weeks prior to screening or during the screening period or change in erythropoietin dose during last month.
14. Any acute or chronic infection, viral or bacterial within 4 weeks prior to screening or during the screening period that, according to investigator's judgement, is considered as systemic infection.
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of adverse events, either spontaneously reported or resulting from safety and tolerability. |
Inzidenz unerwünschter Ereignisse, entweder spontan berichtet oder anhand der Erhebungen zur Sicherheit und Verträglichkeit festgestellt. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety parameters will be evaluated after IMP administration throughout the treatment and follow up periods. |
Parameter zur Erhebung der Sicherheit/Verträglichkeit werden nach Verabreichung des Prüfpräparates während der Behandlungs- und Nachbeobachtungsphase beurteilt. |
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E.5.2 | Secondary end point(s) |
• PK of NOX-H94 after single and repeat i.v. doses of IMP in dialysis patients
• PD of NOX-H94 after single i.v. dose of NOX H94 evaluated through serum iron concentration changes
• PD and efficacy of NOX-H94 after repeated doses of NOX-H94 evaluated through changes in serum ferritin, soluble transferrin receptors (sTfR), interleukin-6, reticulocyte haemoglobin content (CHr), mean corpuscular haemoglobin (MCH), Hb and reticulocytes
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• PK von NOX-H94 nach einmaliger und wiederholter i.v. Verabreichung des Prüfpräparates bei Dialysepatienten
• PD von NOX-H94 nach i.v. Einmalgabe von NOX-H94, beurteilt anhand der Veränderungen der Serum-Eisenkonzentration
• PD und Wirksamkeit von NOX H94 nach wiederholter Verabreichung von NOX H94, beurteilt anhand der Veränderungen der Serumkonzentrationen von Ferritin, des löslichen Transferrin-Rezeptors (sTFR), von Interleukin-6, des Hämoglobingehalts in den Retikulozyten (CHr), des mittleren Hämoglobingehalts pro Erythrozyt (MCH), des Hb-Werts und der Retikulozytenzahl |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK endpoints assessed at the following timepoints:
Group 1: Day 8, 9, 10, 12, 15, 22 and 36
Groups 2/3: Day 1, 3, 8, 15, 22, 29, 36, 43 and 57
Pharmacodynamics and efficacy endpoints:
Group 1: Day 1, 2, 8, 9, 10, 12, 15 and 22
Groups 2/3: Day 1, 8, 15, 22, 29, 36 and 43 |
PK Endpunkte werden zu folgenden Zeitpunkten beurteilt:
Gruppe 1: Tag 8, 9, 10, 12, 15, 22 und 36.
Gruppe 2/3: Tag 1, 3, 8, 15, 22, 29 36, 43 und 57.
Pharmakodynamik und Wirksamkeitsendpunkte:
Gruppe 1: Tag 1, 2, 8, 9, 10, 12, 15 und 22
Gruppe 2/3: Tag 1, 8, 15, 22, 29, 36 und 43 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Single-blind, cross-over for Group 1 only |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
Letzter Patient letzer Besuch |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |