| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
CHRONIC HEPATITIS B VIRUS,TRANSPLANT
Hepatitis Cronica por viris B, Transplante |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10019743 |
| E.1.2 | Term | Hepatitis B virus (HBV) |
|
| 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). |
|
| 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| 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 diameter 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 (>=16 years of age or minimum age of consent in a given
country)
|
|
| 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
contraindicated contraceptives to entecavir.
3) Women who are pregnant or breastfeeding
4) Women with a positive pregnancy test on 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 hrs
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 IU/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, it must be repeated. If the repeat alpha fetoprotein level is between 21 and 100 ng/mL and if ultrasonography or computerized tomography (CT) of the liver performed prior to the first dose 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 |
|
| 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).
|
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| 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.8.3 |
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 | 9 |
| 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 |
|
| 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
|
|
| 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 | 0 |
| 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 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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