Overview

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

Status:
Completed
Trial end date:
2016-01-01
Target enrollment:
0
Participant gender:
All
Summary
The primary objectives of this study are to compare the efficacy, safety, and tolerability of tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) for the treatment of HBeAg-positive chronic hepatitis B. Participants will receive TDF or ADV for 48 weeks (double-blind). After 48 weeks, eligible participants switched to open-label TDF for up to 480 weeks.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Gilead Sciences
Treatments:
Adefovir
Adefovir dipivoxil
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Tenofovir
Criteria
Key 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 more than 6 months

- 18 through 69 years of age, inclusive

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

- HBeAg positive at screening

- Alanine aminotransferase (ALT) levels > 2 × ULN and ≤ 10 × the upper limit of the
normal range (ULN)

- Serum HBV DNA > 1 million 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
96 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible
for enrollment

- Negative serum β-human chorionic gonadotropin (hCG)

- Nucleotide naïve, ie, no prior nucleotide (TDF or ADV) therapy for > 12 weeks

- Nucleoside naïve, ie, no prior nucleoside (any nucleoside) therapy for > 12 weeks

- Willing and able to provide written informed consent

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

Key Exclusion Criteria:

A patient who meets any of the following exclusion criteria is not to be enrolled in this
study:

- Pregnant women, women who are breast feeding or 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; for males, condoms should be used and for
females, a barrier contraception method should be used

- 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), ie, α-fetoprotein >50 ng/mL

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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.