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 a negative status for the AgeHB - and a positive status for the AbeHB in the selection and at least once> 4 weeks before the 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; • 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 selection period; • Evidence of chronic hepatitis on liver biopsy performed 3.0 g / dL (> 30 g / L), o 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 study drug administration.
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 umol / L); • Antinuclear antibody (ANA) titre> 1: 160, unless attributable to non-hepatic disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Improvement of 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 End Point Timepoints:Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:A Compound Endpoint consisting of a non-detectable level of HBV DNA measured with the Quantiplex assay (formerly Chiron, detection limit of 0.7 MEq / mL or 2.5 pg / mL) and normal ALT at Week 48 Measure:Level of HBV DNA Timepoints:Week 48 ; Outcome name:(HBV DNA not detectable with the Quantiplex assay) at Week 48 Measure:Virological Response Timepoints:Week 48 ; Outcome name:Normalization of serum ALT at Week 48 Measure:Serum AL 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 the Week 48. HBV DNA will also be evaluated as a continuous parameter Measure:Non-detectable levels of HBV DNA by the Amplicor PCR Timepoints:Week 48 ; Outcome name:Hepatic cccDNA test Measure:Reduction of hepatic cccDNA at Week 48 compared to baseline Timepoints:Week 48 ; Outcome name:An increase in HBV-DNA of> 1 log10 according to the Quantiplex assay 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 during treatment with the study drug Timepoints:Week 48 ; Outcome name:Non-detectable level of HBV DNA by the Quantiplex assay and normal ALT for 24 weeks without treatment Measure:The persistence of the response for the Compound Endpoint Timepoints:24 weeks ; Outcome name:In subjects who have a Virological Response at Week 48, the return of HBV DNA levels (as measured by the Quantiplex DNA assay) will be assessed at baseline or at a higher level at 24 weeks without treatment. Measure:HBV DNA levels Timepoints:24 weeks ; Outcome name:The Response to the Compound Endpoint after an additional 48 weeks of treatment (Week 96) for subjects who have had a Virological Response but not yet. have achieved a Response to the Compound En | — |
Outcome results
None listed