E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CHRONIC HEPATITIS B VIRUS,TREATMENT-NAIV |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019731 |
|
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 compare the proportion of subjects in each treatment group who achieve HBV DNA < 50 IU/mL (approximately 300 copies/mL) by PCR at Week 96 of treatment using the Roche COBAS TaqMan HBV Test for use with the High Pure System (HPS) assay. |
|
E.2.2 | Secondary objectives of the trial |
Compare ETV+TDF combination vs ETV monotherapy for: *Proportion of subjects 1.(HBeAg-positive) achieving HBV DNA <50 IU/mL(+/- 300 copies/mL) by PCR at WK48 & 96;2.(HBeAg-negative) achieving HBV DNA <50 IU/mL by PCR at WK48 & 96;3.who achieve HBV DNA <50 IU/mL by PCR at WK48;4.who achieve HBV DNA <LLD for Roche COBAS TaqMan-HPS assay at WK48 & 96;5.with HBV DNA in relevant categories: <LLD(4.8 IU/mL); LLD(4.8 IU/mL) to <50; 50 to <172; 172 to <1,720; 1,720 to <17,200; and >=17,200 IU/mL at WK48 & 96;6.with ALT normalization (=<1 x ULN) at WK48 & 96;7.(HBeAg-positive at baseline) with loss of HBeAg at WK48 & 96;8.(HBeAg-positive at baseline)with HBe seroconversion(HBeAg loss & presence of HBeAb)at WK48&96;9.with HBsAg loss & HBs serconversion at WK48 & 96;*Mean log10 reduction from baseline in HBV DNA by PCR at WK48 & 96;*Frequency of AEs,SAEs & study drug discontinuations due to AEs/laboratory abnormalities; *Evaluate ETV resistance profile in combination vs monotherapy |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1)Signed written informed consent 2)Nucleoside- and nucleotide-naïve subjects with chronic HBV infection (detectable HBsAg at screening and for at least 24 weeks prior to screening, or detectable HBsAg for < 24 weeks and negative for IgM core antibody); 3)Subjects must have compensated liver function and must meet ALL of the following criteria: International Normalization Ratio (INR) =< 1.5 Serum albumin >= 3 g/dL (>= 30 g/L) Serum total bilirubin =< 2.5 mg/dL (=< 42.75 µmol/L) 4)For HBeAg-positive subjects, HBV DNA > 172,000 IU/mL (approximately 1,000,000 copies/mL) by PCR at screening; OR For HBeAg-negative subjects, HBV DNA >17,200 IU/mL (approximately 100,000 copies/mL) by PCR at screening; 5)ALT >= 1.3 x the ULN at screening and at least once >= 12 weeks prior to screening; 6)Males and females >= 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 or tenofovir; 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)Evidence of decompensated cirrhosis including but not limited to: variceal bleeding; hepatic encephalopathy; or ascites requiring management with diuretics or paracentesis; 7)Coinfection with HIV, hepatitis C virus ([HCV]; coinfection is defined as HCV Ab-positive with detectable HCV ribonucleic acid [RNA] by PCR), or hepatitis D virus (HDV); 8)Recent history of pancreatitis (within 24 weeks prior to the first dose of study medication); 9)Currently abusing illegal drugs or alcohol sufficient, in the Investigators opinion, to prevent adequate compliance with study therapy or to increase the risk of hepatotoxicity or pancreatitis; 10)Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications (see Exclusion Criterion 19); 11)Serum creatinine > 1.5 mg/dL; 12)Hemoglobin < 10.0 g/dL; 13)Platelet count < 70,000/mm³; 14)Absolute neutrophil count < 1500 cells/mm³; 15)Serum alpha fetoprotein (AFP) level > 100 ng/mL; If the AFP level is between 21 and 100 ng/mL, it must be repeated prior to randomization. If the repeat AFP 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, the subject may be dosed in the study; 16)Known history of allergy to nucleoside or nucleotide analogues; 17)Any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., adefovir, entecavir, famciclovir, tenofovir, telbivudine, clevudine, emtracitabine), or any other experimental anti-HBV antiviral; 18)Therapy with interferon; thymosin alpha or other immuno-stimulators within 24 weeks of randomization into this study; 19)Required chronic administration of medications which cause immunosuppression or which are associated with a high risk of nephrotoxicity or hepatotoxicity or which affect renal excretion (See Protocol Section 5.5.1 for examples); 20)Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study; 21)Unable to tolerate oral medication; 22)Poor peripheral venous access |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects who achieve HBV DNA < 50 IU/mL (approximately 300 copies/mL) by PCR at Week 96 of treatment using the Roche COBAS TaqMan HBV Test for use with the High Pure System (HPS) assay |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
ETV+TDF combination treatment vs ETV monotherapy |
|
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 |
|
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
| |
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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |