None listed
Conditions
Interventions
Sponsors
BRISTOL MYERS SQUIBB PERU S.A.,
Eligibility
Inclusion criteria
Inclusion criteria: • Men and women> 16 years of age (or the minimum age required in each country), with a history of chronic hepatitis B infection; • Detectable levels of HBsAg at the time of selection and for at least 24 weeks before selection; • Documentation of xm positive status for hepatitis B antigen (AgeHB) in the selection and at least once> 4 weeks before selection; • ALT from 1.3 to 10 x the normal maximum limit (LMN) in the selection and at least once> 12 weeks before the selection; • Serum level of HBV DNA detectable at least once with any commercial assay (Abbott, Digene, RCP)> 4 weeks before selection and> 3.0 MEq / mL (10.6 pg / mL) with the Quantiplex assay in the period of selection; • Evidence of chronic hepatitis on liver biopsy performed 3.0 g / dL (> 30 g / L), • Absence of current evidence or history of variceal bleeding, hepatic encephalopathy or ascites requiring diuretics or paracentesis or evidence of these conditions in the physical examination performed for this study. • All women of childbearing age (MEE) must have a negative pregnancy test in serum or urine (minimum sensitivity of 25 IU / L of HCG) within 72 hours before the start of administration-of the study drug. Lamivudine 100 mg once a day for 52 weeks
Exclusion criteria
Exclusion criteria: • Concomitant infection by human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV); • Other forms of liver disease, eg, alcoholic, autoimmune, biliary; • Therapy with interferon, thymosin alfa or antiviral agents with activity against hepatitis B (adefovir, famciclovir and lamivudine) in the 24 weeks immediately prior to randomization in this study; • More than 12 weeks of previous treatment with antiviral agents with activity against hepatitis B (for example, adefovir, famciclovir and lamivudine); • Previous therapy with entecavir; • Known antecedents of allergy to nucleoside analogues; • Hemoglobin 1.5 mg / dL (> 133 mmol / L); • Antinuclear antibody (ANA) titre> 1: 160, unless attributable to non-hepatic diseases. • Recent history of pancreatitis (in the 24 weeks prior to the administration of the first dose of study medication); • Alpha fetoprotein serum level of> 100 ng / mL. If the alpha fetoprotein level is 21 to 100 ng / mL, the test should be repeated. If in the second determination the alpha fetoprotein level is 21 to 100 ng / mL and the ultrasonography or computed tomography (CT) of the liver performed before the administration of the first dose of the study drug does not demonstrate a focal lesion that suggests carcinoma, the subject may receive the study treatment; • Current abuse of alcohol or illegal drugs sufficient, in the opinion of the Investigator, to prevent the adequate compliance of the study therapy or increase the risk of hepatotoxicity; • Women who are pregnant or breastfeeding; • Sexually active subjects who are not surgically sterile and who are unwilling to practice reliable contraception (oral, injectable or implantable contraceptive medication approved, intrauterine device, diaphragm, condom with jelly or spermicidal formula, or sexual abstinence) during treatment and up to 8 weeks after stopping the study medication. • Inability to tolerate oral medications; • Deficiency of the peripheral venous access that, in the opinion of the investigator, prevents the frequent extraction of blood samples; • Participation in a clinical study in the 30 days immediately prior to randomization; • Other serious medical conditions that could prevent the completion of this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Improvement in necroinflammatory score (reduction of> 2 points in the HAI scale of Knodell), without a worsening of fibrosis (increase of> 1 point in the scale of evaluation of Knodells fibrosis) in the liver biopsy of Week 48 compared to the baseline. Measure:Proportion of subjects in each treatment group that achieve the Histological Endpoint, Timepoints:Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Non-detectable level of HBV DNA measured with the Quantiplex assay (detection limit of 0.7 MEq / mL or 2.5 pg / mL) and loss of AgeHB at Week 48 Measure:Total Virological Response Timepoints:Week 48 ; Outcome name:HBV DNA not detectable with the assay Quantiplex, but positive status for AgeHB at Week 48 Measure:Partial Virological Response Timepoints:Week 48 ; Outcome name:Loss of AgeHB, increase of AbeHB Measure:Seroconversion to Week 48 Timepoints:Week 48 ; Outcome name:Serum ALT measurement Measure:Normalization of serum ALT to Week 48 Timepoints:Week 48 ; Outcome name:Non-detectable level of HBV DNA measured with the Quantiplex assay (detection limit of 0.7 MEq / mL or 2.5 pg / mL) and loss of AgeHB at Week 48 Measure:Normalization of serum ALT to Week 48 Timepoints:Week 48 ; Outcome name:Non-detectable levels of HBV DNA by the Roche Amplicor PCR assay (limit of detection of 400 copies / mL) at Week 48. HBV DNA will also be evaluated as a continuous parameter Measure:Non-detectable levels of HBV DNA by Amplicor PCR assay Timepoints:Week 48 ; Outcome name:Measurement of the hepatic cccDNA Measure:Reduction of hepatic cccDNA at Week 48 compared to baseline Timepoints:Week 48 ; Outcome name:Elevation of the HBV DNA titer (increase of> 1 log10 according to the Quantiplex assay) during treatment with the study drug, after initially non-detectable levels were achieved with the drug. A genotypic analysis of these HBV isolates will be carried out to detect the presence of mutations Measure:Resistance to therapy Timepoints:Week48 ; Outcome name:Non-detectable level of HBV DNA measured with the Quantiplex assay (detection limit of 0.7 MEq / mL or 2.5 pg / mL) and loss of AgeHB Measure:Persistence of the Total Virological Response for 24 weeks without treatment Timepoints:24 weeks ; Outcome name:In subjects who have a Total | — |
Outcome results
None listed