Chronic Hepatitis B MedDRA version: 16.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Gilead Sciences Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Chronic HBV infection, defined as positive serum HBsAg for at least 6 months. 2) 18 through 69 years of age, inclusive. 3) Active HBeAg negative chronic HBV infection, with all of the following: • HBeAg negative and HBeAb positive at screening • ALT levels > ULN and = 10 x ULN • Serum HBV DNA > 100000 copies/mL at screening • creatinine clearance = 70 mL/min • hemoglobin = 8 g/dL • neutrophils = 1,000 /mm3 4) Knodell necroinflammatory score = 3 and a Knodell fibrosis score =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1) Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study. 2) Males and females of reproductive potential who are unwilling to use an “effective” method of contraception during the study. For males, condoms should be used and for females, a barrier contraception method should be used. 3) Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, PT > 1.5 x ULN, platelets 50 ng/mL or by any other standard of care measure. 6) Co-infection with HCV, HIV, or HDV. 7) Significant renal, cardiovascular, pulmonary, or neurological disease. 8) Received solid organ or bone marrow transplantation. 9) Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion. 10) Has proximal tubulopathy. 11) Known hypersensitivity to the study drugs, the metabolites or formulation excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) To compare the efficacy of tenofovir DF 300 mg QD versus adefovir dipivoxil 10 mg QD for the treatment of presumed pre-core mutant chronic hepatitis B at Week 48. The primary efficacy parameter is the proportion of patients with complete response, i.e., serum HBV DNA levels below 400 copies/mL and histologic improvement defined as at least a 2 point reduction in the Knodell necroinflammatory score without worsening in Knodell fibrosis score. 2) To compare the safety and tolerability of tenofovir DF 300 mg QD versus adefovir dipivoxil 10 mg QD for the treatment of presumed pre-core mutant chronic hepatitis B at 48 weeks. ; Secondary Objective: 1) To compare the incidence of drug resistant mutations between treatment arms at Week 48 and every 48 weeks thereafter. 2) To compare the virological, biochemical, serological and histological response to tenofovir DF 300 mg QD versus adefovir dipivoxil 10 mg QD for the treatment of presumed pre-core mutant chronic hepatitis B at Week 48. 3) To evaluate persistent virological response (i.e., serum HBV DNA <400 copies/mL) between randomized treatment arms post week 48. 4) To compare the virological, biochemical, serological and histological response of continuous treatment of tenofovir DF (early) versus sequential treatment of tenofovir DF (deferred; 48 weeks of adefovir dipivoxil followed by tenofovir DF treatment). 5) To evaluate the durability of the serological response from Weeks 48 to 384 or 480 once study drug is discontinued. 6) To evaluate the activity of combination therapy (tenofovir DF 300 mg/ emtricitabine 200 mg) following persistent viral replication. ;Timepoint(s) of evaluation of this end point: 48 weeks;Primary end point(s): The primary efficacy parameter is the proportion of patients treated with tenofovir DF 300 mg QD versus adefovir dipivoxil 10 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints are change from baseline in log10 serum HBV DNA and ALT levels, proportion of patients with serum HBV DNA below 400 copies/mL, percentage of patients with normal ALT, incidence of drug resistant mutations, percentage of patients with HBsAg loss and seroconversion, percentage of patients with histological improvement, change from baseline in histological scores (to include Ishak), and ranked assessment of histological scores.;Timepoint(s) of evaluation of this end point: Week 48 | — |
Countries
Australia, Canada, Czech Republic, Germany, Italy, New Zealand, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactEU Legal Representative for GSI
Gilead Sciences International Ltd
Outcome results
None listed