E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Erythropoiesis stimulating agents (ESA) hyporesponsive anaemia in dialysis patients |
Anemia iporesponsiva agli agenti stimolanti l'eritropoiesi (ESA) in pazienti in dialisi |
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E.1.1.1 | Medical condition in easily understood language |
Anaemia in dialysis patients that does not respond to agents (ESA) that stimulate red cell production |
Anemia in pazienti in dialisi che non rispondono agli agenti (ESA) che stimolano la produzione di globuli rossi |
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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 | 20.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 | 20.0 |
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.1.3 | 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 |
Determinare la sicurezza e la tollerabilit¿ di dosi singole e ripetute di NOX H94 in pazienti in dialisi |
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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 |
¿ Studiare la farmacocinetica con particolare riguardo all¿accumulo nel plasma e all¿eliminazione, la farmacodinamica e l¿efficacia di NOX H94 in pazienti in dialisi con deficit funzionale di ferro ¿ Ottenere primi dati sull¿efficacia di NOX-H94 in termini di risposta dell¿Hb |
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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 |
1. Consenso informato scritto 2. Uomini o donne non fertili 3. Età da 18 a 85 anni 4. Nefropatia terminale trattata con emodialisi di mantenimento da =3 mesi, 3 volte alla settimana 5. Anemia: Hb da 7 a 11 g/dL 6. Deficit funzionale di ferro: saturazione della transferrina <30%, ferritina =300 ng/mL. 7. Iporesponsività agli ESA con una dose di eritropoietina =12.000 UI/settimana, stabile da =4 settimane |
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E.4 | Principal exclusion criteria |
1. Inability to personally provide written informed consent or to understand 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. |
1. Incapacità a fornire personalmente il consenso informato scritto o a intendere e collaborare per l’intera durata dello studio. 2. Incapacità o rifiuto ad attenersi alle restrizioni imposte nell’ambito dello studio. 3. Partecipazione ad un qualsiasi studio di ricerca clinica riguardante un farmaco o una terapia sperimentale nei 30 giorni precedenti la visita di screening o l’arruolamento in questo studio. 4. Gravidanza o allattamento. 5. Trattamento con darbepoetina o metossi-polietilenglicole-epoetina. 6. Malattia cardiovascolare non controllata, arteriopatia periferica o malattia cerebrovascolare instabile, ipertensione non controllata (pressione sistolica >180 mm Hg o pressione diastolica >100 mm Hg). 7. Insufficienza cardiaca congestizia: classe III o IV secondo la New York Heart Association. 8. Angina instabile, infarto miocardico, angioplastica coronarica percutanea transluminale/stent o bypass coronarico <3 mesi prima dello screening. 9. Qualsiasi altra malattia che richieda una modifica della terapia nelle 4 settimane precedenti lo screening o renda inopportuna la partecipazione allo studio (a discrezione dello sperimentatore). 10. Emolisi e/o emorragia clinicamente rilevante all’anamnesi. 11. AST, ALT o bilirubina =2,0 volte il limite superiore della norma. 12. Fibrosi midollare nota. 13. Trattamento con ferro e.v. <4 settimane prima dello screening o durante il periodo di screening o modifica della dose di eritropoietina nel mese precedente. 14. Qualsiasi infezione acuta o cronica, virale o batterica, nelle 4 settimane precedenti lo screening o durante il periodo di screening, che sia considerata sistemica a giudizio dello sperimentatore. |
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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. |
Incidenza degli eventi avversi, sia da segnalazioni spontanee che da valutazioni di sicurezza e tollerabilità. |
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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. |
I parametri di sicurezza saranno valutati dopo la somministrazione del farmaco durante tutto il corso del trattamento e dei periodi di follow-up. |
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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. |
¿ PK di NOX H94 dopo dosi e.v. singole e ripetute dell¿IMP in pazienti in dialisi; ¿ PD di NOX H94 dopo una dose singola e.v. di NOX H94, determinata mediante le variazioni della concentrazione di ferro sierico; ¿ PD ed efficacia di NOX H94 dopo dosi ripetute di NOX H94, determinate mediante le variazioni dei livelli di ferritina sierica, del recettore solubile della transferrina (sTfR), dell¿interleuchina 6, della concentrazione di emoglobina reticolocitaria (CHr), dell¿emoglobina corpuscolare media (MCH), dell¿Hb e dei reticolociti.
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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 |
Gli endpoint di farmacocinetica saranno rilevati ai seguenti periodi: Gruppo 1: Giorno 8, 9, 10, 12, 15, 22 e 36 Gruppi 2/3: Giorno 1, 3, 8, 15, 22, 29, 36, 43 e 57 Gli endpoint di farmacodinamica e di efficacia ai seguenti: Gruppo 1: Giorno 1, 2, 8 ,9, 10, 12, 15 e 22 Gruppi 2/3: Giorno 1, 8, 15, 22, 29, 36 e 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 |
Singolo cieco, cross-over solo per il Gruppo 1 |
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 | 4 |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |