Tenofovir Disoproxil Fumarate (Tenofovir DF) Versus Emtricitabine/Tenofovir DF in Subjects Resistant to Lamivudine
Information source: Gilead Sciences
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatitis B
Intervention: TDF (Drug); FTC/TDF (Drug); Placebo to match TDF (Drug); Placebo to match FTC/TDF (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Gilead Sciences Official(s) and/or principal investigator(s): John Flaherty, PharmD, Study Director, Affiliation: Gilead Sciences
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
Secondary outcome: Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96HBV DNA Level at Week 96 Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 96 Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had HBeAg Loss at Week 96 Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had Seroconversion to Antibody Against HBeAg (Anti-HBe) at Week 96 Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Week 96 Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Week 96 Percentage of Participants With Virologic Breakthrough at Week 96 Percent Change From Baseline in Mean Bone Mineral Density (BMD) of the Spine at Week 24 Percent Change From Baseline in Mean BMD of the Spine at Week 48 Percent Change From Baseline in Mean BMD of the Spine at Week 72 Percent Change From Baseline in Mean BMD of the Spine at Week 96 Percent Change From Baseline in Mean BMD of the Hip at Week 24 Percent Change From Baseline in Mean MD of the Hip at Week 48 Percent Change From Baseline in Mean BMD of the Hip at Week 72 Percent Change From Baseline in Mean BMD of the Hip at Week 96 Development of Drug-resistant Mutations (DRMs)
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Innsbruck A-6020, Austria
Wien A-1090, Austria
Wien A-1130, Austria
Sofia 1527, Bulgaria
Sofia 1606, Bulgaria
Sofia 1407, Bulgaria
Varna 9010, Bulgaria
Brno 625 00, Czech Republic
Plzen 304 60, Czech Republic
Prague 160 00, Czech Republic
Praha 4 14021, Czech Republic
Usti Nad Labem 40001, Czech Republic
Berlin 13353, Germany
Duesseldorf 40225, Germany
Essen 45122, Germany
Frankfurt 60590, Germany
Hamburg 20099, Germany
Hannover 30625, Germany
Stuttgart, Germany
Larissa 41110, Greece
Patras 25404, Greece
Thessaloniki 54642, Greece
Budapest 1126, Hungary
Debrecen 4032, Hungary
Gyula H5700, Hungary
Kasposvar H7400, Hungary
Auckland, New Zealand
Hamilton, New Zealand
Wellington 6035, New Zealand
Bialystok 15-540, Poland
Bydgoszcz 85-030, Poland
Chorzow 41-500, Poland
Krakow 31-351, Poland
Lodz 91-347, Poland
Szczecin 71-455, Poland
Warszawa 01-201, Poland
Warszawa 02-507, Poland
Wroclaw 50-220, Poland
Bucharest 021105, Romania
Bucharest 030303, Romania
Bucharest 022328, Romania
Bucuresti 020125, Romania
Bucuresti 021105, Romania
Bucuresti 022328, Romania
Cluj-Napoca 400158, Romania
Constanta 900708, Romania
Belgrade 11000, Serbia
Kragujevac 34000, Serbia
Nis 18000, Serbia
Novi Sad 21000, Serbia
Sevilla 4103, Spain
Ankara 06100, Turkey
Bursa 16059, Turkey
Izmir 35100, Turkey
Samsun 55139, Turkey
Trabzon 61080, Turkey
Uskudar 34668, Turkey
Ulm, Baden-Wuerttemberg 89081, Germany
Vancouver, British Columbia V6Z 2K5, Canada
Vancouver, British Columbia V6AB46, Canada
Vancouver, British Columbia V5Z, Canada
Bradenton, Florida 34205, United States
Timisoara, Judetul Timis 300736, Romania
Lasi, Judetul lasi 700111, Romania
Winnepeg, Manitoba R3E 3P4, Canada
Flushing, New York 11355, United States
Toronto, Ontario M5G 1X5, Canada
Toronto, Ontario M5G 2C4, Canada
Toronto, Ontario M6H 3M1, Canada
Toronto, Ontario M5T 2S8, Canada
Philadelphia, Pennsylvania 19107, United States
Additional Information
Starting date: September 2008
Last updated: February 19, 2015
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