Patients with chronic HBV infection MedDRA version: 9.1 Level: LLT Classification code 10008910
Conditions
Interventions
Trade Name: BARACLUDE
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ENTECAVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Sponsors
AZIENDA OSPEDALIERA SPEDALI CIVILI DI BRESCIA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed written informed consent 1) Freely given informed consent must be obtained from subjects prior to clinical trial participation, including informed consent for any screening procedures conducted to establish subject eligibility for the study; 2) Patients with chronic HBV infection (detectable HBsAg at screening and for at least 24 weeks prior to screening, or detectable HBsAg for ULN and ≤ 10 x ULN and HBVDNA >/= 2000 IU/ml at screening and at least once ≥ 12 weeks prior to screening; 4) Fibrosis stage at liver histology >/= 2 by METAVIR scoring in a biopsy performed no more than 6 months before study entry; 5) 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) 6) Nucleoside- and Nucleotide-naive subjects (previous recombinant interferon or pegylated interferon based therapy is admitted if it was withdrawn 6 months before study entry; 7) Males and females ≥ 18 years of age Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. WOCBP must have a negative serum or urine pregnancy test within 72 hours prior to the start of investigational product. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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; Target Disease Exceptions 5) Evidence of clinical condition correlated to liver disease for which, in the Investigator s opinion, NAs are mandatory; 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 (coinfection is defined as HCV Ab positive with detectable HCV RNA by PCR) or hepatitis D virus; Medical History and Concurrent Diseases 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 Investigator s 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); Physical and Laboratory Test Findings 11) 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; Allergies and Adverse Drug Reactions 12) Known history of allergy to NAs;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the proportion of subjects which could be considered for NAs and for which NAs are not mandatory according to EASL guidelines ,with evolution of liver fibrosis after three years of follow up in a group of patients started on Entecavir versus a group of patients in which therapy is deferred.;Secondary Objective: To assess the impact of Entecavir treatment on biochemical and virological parameters and on the rate of adverse events. To identify the diagnostic and predictive value of liver stiffness estimated by transient elastometry (Fibroscan) and of non-invasive fibrosis serum markers ( Fibrotest, Forns, APRI, Fibroindex, FPI, FIB-4, Bonacini, SHASTA, Fibrometer, Hepascore) assessed at baseline and once a year after study entry on: - Definition of the stage of liver fibrosis (according to Metavir score) at baseline and at the end of the study; - Evaluation of the predictive value on the change of liver fibrosis stage (by METAVIR and Ishak s scores) at baseline and at the end of the study.;Primary end point(s): Proportion of subjects (who were HBeAg-positive at baseline) with anti HBe seroconversion (HBeAg loss and presence of HBeAb); proportion of subjects with HBsAg loss and HBs serconversion; proportion of subjects with ALT normalization (≤ 1 x ULN) proportion of subjects who achieve and maintain undetectable HBV DNA until the end of the study rate of resistance mutations; frequency of adverse events (AEs), including modification of creatinine clearance, phosphatemia and phosphaturia values, serious adverse events (SAEs) and discontinuations from study due to adverse events or laboratory abnormalities; rate of adherence; rate of drops out; modification of liver stiffness assessed by Fibroscan and of the score obtained by the non-invasive serum markers (Fibrotest, Forns, APRI, Fibroindex, FPI, FIB-4, Bonacini, SHASTA, Fibrometer, Hepascore) in the two groups | — |
Countries
Italy
Outcome results
None listed