E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis B re-infection |
Re-infezione da epatite B |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis B infection re-occurence |
Ricadute di infezione da epatite B |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058827 |
E.1.2 | Term | Hepatitis B reactivation |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 investigate the efficacy of Zutectra in orthotopic liver transplanted patients |
Valutare l'efficacia di Zutectra nei pazienti sottoposti a trapianto di fegato |
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E.2.2 | Secondary objectives of the trial |
To demonstrate safety of Zutectra in orthotopic liver transplanted patients To assess the number of Hepatitis B virus re-infections of the liver (HBsAg positive and clinical symptoms) |
Dimostrare la sicurezza di Zutectra in pazienti sottoposti a trapianto di fegato Valutare il numero di re-infezioni del fegato da virus dell'epatite B (HBsAg positivo e sintomi clinici) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent obtained prior to orthotopic liver transplantation (OLT) - not more than 3 months before OLT 2. Historical evidence within the last 4 weeks that HBV-DNA is undetectable at time point of signature of Informed Consent 3. Male and female patients (age 18-75 years) 4. Patients with the diagnosis of liver failure with hepatitis B infection 5. Patients undergoing liver transplantation or re-transplantation 6. HBsAg negative on day 7 or on day 14 after OLT 7. HBV-DNA undetectable at OLT 8. Serum HBs antibody concentration on day 7 or on day 14 after OLT ≥ 400 IU/l 9. Stable patient in a condition which in the opinion of the investigator would permit safe participation in the study 10. Willingness to fill out patient diary |
1. Consenso informato scritto ottenuto prima deltrapianto di fegato ortotopico(OLT)- non più di 3 mesi prima dell’OLT 2. L'evidenza storica, nell’arco delle ultime 4 settimane, che l’HBV-DNA non è rilevabile al momento della firma del consenso informato 3. Pazienti di sesso maschile e femminile (età 18-75 anni) 4. Pazienti con diagnosi di insufficienza epatica associata a infezione da epatite B 5. Pazienti sottoposti a trapianto di fegato o ri-trapianto 6. HBsAg-negativi il giorno 7 o il giorno 14 in seguito all’OLT 7. HBV-DNA non rilevabile al momento dell’OLT 8. Concentrazione di anticorpi HBs nel siero il giorno 7 o il giorno 14, in seguito all’OLT≥400 UI / l 9. Paziente stabile in una condizione che, a parere dello sperimentatore, consentirebbe la partecipazione sicura allo studio 10. Disponibilità a compilare il diario del paziente |
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E.4 | Principal exclusion criteria |
1. Re-transplantation due to viral recurrence 2. Positive HIV or HCV test at time of transplantation 3. HBV-DNA positive at OLT 4. Patients having received organs from HBsAg positive donors 5. Pregnancy or unreliable contraceptive measures or lactation period (females only) 6. Known intolerance to immunoglobulins or comparable substances (e.g. vaccination reaction) 7. Known intolerance to proteins of human origin 8. Participation in another interventional clinical trial within 90 days before entering the study or during the study and/or previous participation in this study (except screening failures) 9. Suspicion of drug and/or alcohol abuse 10. Inability or lacking motivation to participate in the study 11. Employee or direct relative of an employee of the CRO, the study site, or Biotest |
1. Ri-trapianto a causa di recidiva virale 2. Positività al test HIV o HCV al momento del trapianto 3. HBV-DNA positivo al momento dell’OLT 4. Pazienti che hanno ricevuto organi da donatori HBsAg positivi 5. Stato di gravidanza o inaffidabili misure contraccettive o in periodo di allattamento (solo per i pazienti di sesso femminile) 6. Nota intolleranza alle immunoglobuline o a sostanze simili (ad esempio reazione alla vaccinazione) 7. Nota intolleranza alle proteine di origine umana 8. La partecipazione ad un altro studio clinico interventistico entro 90 giorni prima di entrare in studio o durante lo studio e/o prima della partecipazione a questo studio (fatta eccezione per errori di screening) 9. Sospetto di abuso di droga e/o alcool 10. Incapacità o mancanza di motivazione a partecipare allo studio 11. Dipendente o parente diretto di un dipendente della CRO, del centro dello studio, o di Biotest |
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E.5 End points |
E.5.1 | Primary end point(s) |
The failure rate after 24 weeks of treatment based on the trough levels of serum anti-HBs ≤100 IU/l and the number of hepatitis B related reinfections in patients with trough levels of serum anti-HBs > 100 IU/l. |
Percentuale di fallimento dopo 24 settimane di trattamento sulla base dei livelli di anti-HBs nel siero ≤100 IU/l e numero di re-infezioni correlate all'epatite B nei pazienti con livelli minimi di anti-HBs nel siero > 100 UI/l |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of 24 weeks of treatment, or at a re-occurence of infection. |
Al termine delle 24 settimane di trattamento, o alla recidiva di infezione. |
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E.5.2 | Secondary end point(s) |
Efficacy - The number of all patients with hepatitis B related infections will be assessed by monitoring of clinical signs, liver function and measurement of HBsAg and HBV-DNA. Efficacy - serum anti-HBs concentrations Safety - Adverse Event profile, heamatology, clinical chemistry and urinalysis |
Efficacia - verrà valutato il numero di tutti i pazienti con infezioni da epatite B attraverso il monitoraggio dei sintomi clinici, della funzionalità epatica e la misurazione di HBsAg e HBV-DNA. Efficacia - concentrazioni sieriche di anti-HBs Sicurezza - profilo degli Eventi Avversi, ematologia, chimica clinica e analisi delle urine |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Adverse Events - each visit Hepatitis serology - weekly for the first 8 weeks, then monthly until week 24. |
Eventi Avversi - ogni visita Epatite su siero - settimanalmente per le prime 8 settimane, in seguito mensilmente fino alla settimana 24. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |