E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis B Virus, Transplant |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019731 |
E.1.2 | Term | Hepatitis B |
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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 |
Efficacy: to determine the proportion of patients who experience virological recurrence of HBV at 72 weeks post-OLT as measured by HBV DNA by PCR >= 50 IU/ml (approximately >= 300 copies/ml) |
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E.2.2 | Secondary objectives of the trial |
EFFICACY: distribution of ALT levels at week 72; the proportion of patients who remain HBV DNA < 50 IU/ml (approximately <300 copies/ml) at the end of post-dosing follow-up; loss of HBeAg and HBe seroconversion for baseline HBeAg positive subjects will be assessed as counts and proportions; loss of HBsAg and HBs seroconversion at 72 weeks post-OLT will be assessed as counts and proportions. SAFETY: distribution of total bilirubin at week 72; distribution of prothrombin time (PT) at week 72; episodes of liver rejection up to week 72; re-transplant up to week 72; safety as measured by the incidence of adverse events, laboratory abnormalities and discontinuation due to adverse event. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Signed written informed consent; 2. Orthotopic liver transplant (OLT) patients with end-stage liver disease due to chronic HBV infection; 3. HBV DNA <172 IU/ml (approximately <1000 copies/ml) by PCR prior to OLT: fifty (50)subjects with HBV DNA by PCR of <50 IU/ml (approximately 300 copies/ml) at the time of OLT and twenty (20) subjects with HBV DNA by PCR of >= 50 IU/ml and <172 IU/ml (approximately 300 copies/ml and 1000 copies/ml) at the time of OLT; 4. Patients with a pre-OLT diagnosis of hepatocellular carcinoma (HCC) may be enrolled ONLY if there is no evidence of extrahepatic spread, tumor is solitary and =< 6.5 cm in diameter or there are up to three nodules =< 4.5 cm in diameter each, and total tumor is =< 8cm.26; 5. Detectable HBsAg at screening and for at least 24 weeks prior to screening; 6. Patients eligible for OLT according to protocol- specified criteria, in the investigators judgment, are anticipated to receive transplant within 90 days; 7. Male and female adults (>= 18 years of age or minimum age of consent in a given country) |
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E.4 | Principal exclusion criteria |
1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 6 weeks after the last dose of investigational product 2.WOCBP using a prohibited contraceptive method. At this time there are no known controindicated contraceptives to entecavir 3. Women who are pregnant or breastfeeding 4. Women with a positive pregnancy test or enrollment or prior to investigational product administration 5. Sexually active fertile men not using effective birth control if their partners are WOCBP 6. Patients with HCC who do not meet inclusion criteria or require systemic chemotherapy 7. Recipient of ABO blood group incompatible organ 8. Multi-organ or retransplant recipient 9. Donor cold ischemia time >20 hours 10. Co-infection with human immunodeficiency virus (HIV), Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), or hepatitis C virus (HCV) 11. Recent history of pancreatitis (within 24 weeks prior to the first dose of study medication) 12. Currently abusing illegal drugs or alcohol sufficient,in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of hepatotoxicity or pancreatitis 13. Other serious medical conditions that might preclude completion of this study 14. HBV DNA >= 172 UI/ml (approximately >=1000 copies/ml) by PCR prior to OLT 15. Serum alpha fetoprotein level > 100 ng/ml. If the alpha fetoprotein level is between 21 and 100 ng/ml and if ultrasonography or computerized tomograohy(CT) of the liver performed prior to the first dse of study medication does not demonstrate a focal lesion suggestive of carcinoma 16. Known history of allergy to nucleoside analogues 17. Unstable dose schedule (less than 4 weeks) for chronic medications. A consistent dosing schedule is recommended for the duration of study 18. Poor peripheral venous access 19. Unable to tolerate oral medication 20. Prisoners or subjects who are compulsorily detained |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is to determine the proportion of patients who experience virological recurrence of HBV at 72 weeks post-OLT as measured by HBV DNA by PCR>=50 IU/ml (approximately >=300 copies/ml) |
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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 | 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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |