Overview

This trial is active, not recruiting.

Condition hepatitis b
Treatments tenofovir disoproxil fumarate (tenofovir df; tdf), emtricitabine (ftc)/tdf, tdf placebo, ftc/tdf placebo
Phase phase 3
Sponsor Gilead Sciences
Start date September 2008
End date December 2011
Trial size 280 participants
Trial identifier NCT00737568, GS-US-174-0121

Summary

The aim of therapy for the treatment of chronic hepatitis B virus (HBV) is to maintain suppression of viral replication to prevent the emergence of complications, which requires long-term therapy. Durable suppression of viral replication is achieved in the treatment of chronic viral diseases by preventing of the emergence of drug-resistant mutations. The clinical guidelines for the management of lamivudine resistant patients are variable. Some recommend switching to another agent without cross-resistance, while others recommend adding on another agent without cross-resistance. Limited clinical data exists to demonstrate whether tenofovir disoproxil fumarate (tenofovir DF; TDF) is an effective monotherapy for lamivudine resistant patients or if it should be used as part of a combination therapy regimen.

This study was designed to evaluate the effectiveness, safety, and tolerability of tenofovir DF monotherapy versus emtricitabine (FTC)/tenofovir DF combination therapy in participants with chronic HBV with lamivudine resistance (presence of the rtM204I/V mutation with or without the rtL180M mutation) over a 240-week period. Participants in this study must have been receiving lamivudine treatment at the time of enrollment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
tenofovir disoproxil fumarate (tenofovir df; tdf) Viread
TDF 300 mg once daily (QD) plus placebo to match emtricitabine (FTC)/TDF fixed-dose combination tablet QD
ftc/tdf placebo
Placebo to match FTC/TDF QD
(Experimental)
emtricitabine (ftc)/tdf Truvada
FTC 200 mg/TDF 300 mg fixed-dose combination tablet QD plus placebo to match TDF QD
tdf placebo
Placebo to match TDF QD

Primary Outcomes

Measure
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
time frame: Week 96

Secondary Outcomes

Measure
Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96
time frame: Week 96
HBV DNA Level at Week 96
time frame: Week 96
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 96
time frame: Week 96
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had HBeAg Loss at Week 96
time frame: Baseline to Week 96
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had Seroconversion to Antibody Against HBeAg (Anti-HBe) at Week 96
time frame: Baseline to Week 96
Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Week 96
time frame: Baseline to Week 96
Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Week 96
time frame: Baseline to Week 96
Percentage of Participants With Virologic Breakthrough at Week 96
time frame: Week 96
Percent Change From Baseline in Mean Bone Mineral Density (BMD) of the Spine at Week 24
time frame: Baseline to Week 24
Percent Change From Baseline in Mean BMD of the Spine at Week 48
time frame: Baseline to Week 48
Percent Change From Baseline in Mean BMD of the Spine at Week 72
time frame: Baseline to Week 72
Percent Change From Baseline in Mean BMD of the Spine at Week 96
time frame: Baseline to Week 96
Percent Change From Baseline in Mean BMD of the Hip at Week 24
time frame: Baseline to Week 24
Percent Change From Baseline in Mean MD of the Hip at Week 48
time frame: Baseline to Week 48
Percent Change From Baseline in Mean BMD of the Hip at Week 72
time frame: Baseline to Week 72
Percent Change From Baseline in Mean BMD of the Hip at Week 96
time frame: Baseline to Week 96
Development of Drug-resistant Mutations (DRMs)
time frame: Baseline to Week 96

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria - Chronic HBV infection, defined as positive serum HBsAg for at least 6 months - 18 through 75 years of age, inclusive - HBV DNA ≥ 10^3 IU/mL - Receiving treatment with lamivudine with confirmation of HBV reverse transcriptase mutation(s) known to confer resistance to lamivudine (rtM204I/V with or without rtL180M) by central laboratory assessment prior to randomization; adefovir dipivoxil treatment of ≤ 48 weeks at the time of screening (inclusive of combination adefovir dipivoxil + lamivudine at entry) was allowed - Willing and able to provide written informed consent - Negative serum pregnancy test (for females of childbearing potential only) - Calculated creatinine clearance ≥ 50 mL/min - Hemoglobin ≥ 10 g/dL - Neutrophils ≥ 1000 /mm^3 - No prior oral HBV therapy with approved nucleotide and/or nucleoside therapy or other investigational agents for HBV infection other than lamivudine or adefovir dipivoxil Exclusion Criteria - Pregnant women, women who were breast feeding or who believed they may have wished to become pregnant during the course of the study - Males and females of reproductive potential who were not willing to use an effective method of contraception during the study - Alanine aminotransferase (ALT) ≥ 10 × the upper limit of the normal range (ULN) - Decompensated liver disease - Received interferon or pegylated interferon therapy within 6 months of the screening visit - Alpha fetoprotein > 50 ng/mL - Evidence of hepatocellular carcinoma (HCC) - Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV) - Significant renal, cardiovascular, pulmonary, or neurological disease - Received solid organ or bone marrow transplantation - Was receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion - Had proximal tubulopathy - Known hypersensitivity to the study drugs, the metabolites or formulation excipients

Additional Information

Official title A Phase 3b, Randomized, Double-Blind, Double-Dummy Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects With Chronic Hepatitis B Who Are Resistant to Lamivudine
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Gilead Sciences.