A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Negative Chronic Hepatitis B

The efficacy of TDF versus ADV will be evaluated for histologic improvement, reductions in
serum hepatitis B virus deoxyribonucleic acid (HBV DNA), changes in liver enzymes, and the
generation of antibody to the virus. Safety will be assessed by evaluating adverse events,
laboratory abnormalities and the development of drug-resistant mutations. After 48 weeks all
subjects will receive open-label TDF, and the efficacy and safety of TDF will continue to be
monitored for the remainder of the study.

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for
participation in this study:

- Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B
s-antigen (HBsAg) for at least 6 months.

- 18 through 69 years of age, inclusive.

- Active hepatitis B e-antigen (HBeAg) negative chronic HBV infection, with all of the
following:

- HBeAg negative and HBeAb positive at screening

- Alanine aminotransferase (ALT) levels > the upper limit of the normal range
(ULN) and ≤ 10 x ULN

- Serum HBV DNA > 100,000 copies/mL at screening

- Creatinine clearance ≥ 70 mL/min

- Hemoglobin ≥ 8 g/dL

- Neutrophils ≥ 1,000 /mL

- Knodell necroinflammatory score ≥ 3 and a Knodell fibrosis score < 4; however, up to
120 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be
eligible for enrollment

- Negative serum β-human chorionic gonadotropin (hCG)

- Nucleotide naive, ie, no prior nucleotide (TDF or ADV) therapy for greater than 12
weeks

- Nucleoside naive, ie, no prior nucleoside (any nucleoside) therapy for greater than
12 weeks. However, up to 120 patients with > 12 weeks prior lamivudine experience
will be eligible

- Willing and able to provide written informed consent

- Had a liver biopsy performed within 6 months of baseline and has readable biopsy
slides or agrees to have a biopsy performed prior to baseline

Exclusion Criteria:

- Pregnant women, women who are breast feeding, or women who believe they may wish to
become pregnant during the course of the study

- Males and females of reproductive potential who are unwilling to use an effective
method of contraception during the study.

- Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin
time (PT) > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior
history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy,
variceal hemorrhage)

- Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not)
therapy within 6 months prior to the pre treatment biopsy

- Evidence of hepatocellular carcinoma (HCC)

- Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or
hepatitis D virus (HDV)

- Significant renal, cardiovascular, pulmonary, or neurological disease

- Received solid organ or bone marrow transplantation

- Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.),
investigational agents, nephrotoxic agents, or agents susceptible of modifying renal
excretion

- Has proximal tubulopathy