Study Comparing Tenofovir Disoproxil Fumarate (TDF), Emtricitabine (FTC)/TDF, and Entecavir (ETV) in the Treatment of Chronic HBV in Subjects With Decompensated Liver Disease.

Completed · Phase 2 · Has a placebo group

Conditions studied: Chronic Hepatitis B

In brief

This study was designed to evaluate and compare the safety and tolerability of tenofovir disoproxil fumarate (TDF), emtricitabine (FTC)/TDF, and entecavir (ETV) in the treatment of hepatitis B patients with decompensated liver disease. Safety was assessed by evaluating adverse events (AEs) and laboratory abnormalities. Efficacy was assessed by evaluating reductions in Child-Pugh-Turcotte (CPT) and Model for End Stage Liver Disease (MELD) scores, reductions in hepatitis B virus (HBV) deoxyribonucleic acid (DNA), changes in liver enzymes, development of drug-resistant mutations, and generation of antibody to virus. A maximum randomized treatment duration of 168 weeks was planned. Since subjects with decompensated liver disease were enrolled into this study, it was necessary to provide early intervention strategies if profound viral suppression was not expeditiously achieved. For this reason, subjects with a decrease in plasma HBV DNA from baseline of \< 2 log\_10 copies/mL and plasma HBV DNA \> 10,000 copies/mL (or plasma HBV DNA \> 1,000 copies/mL for subjects who entered the study with HBV DNA \< 10,000 copies/mL) at Week 8 had the option to start open-label FTC/TDF and continue in the study. Subjects with a virologic breakthrough or who had plasma HBV DNA levels remaining \> 400 copies/mL (confirmed) at or after 24 weeks of treatment could have been unblinded at the investigator's discretion for selection of alternative anti-HBV therapy that may have included open-label FTC/TDF. If study drug was permanently discontinued, immediate initiation of another anti-HBV regimen was strongly recommended.

Key facts

Study ID: NCT00298363
Run by: Gilead Sciences
People needed: 112
Starts: 2006-04-01
Expected to finish: 2011-04-01
Last updated by the study team: 2013-04-25

Who can join

Age: 18 and older, up to 69. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

A participant was required to meet all of the following inclusion criteria to be eligible for participation in the study:
Chronic Hepatitis B infection
18 through 69 years of age, inclusive
HBV DNA ≥ 1000 copies/mL
Decompensated liver disease with all of the following:
CPT score of 7-12 (inclusive) OR history of CPT score ≥ 7 and any CPT at screen ≤ 12
Serum alanine aminotransferase (ALT) < 10 x the upper limit of the normal range (ULN)
Hemoglobin ≥ 7.5 g/dL
Total white blood cell (WBC) count ≥ 1,500/mm\^3
Platelet count ≥ 30,000/mm\^3
Alpha-fetoprotein ≤ 20 ng/mL and ultrasound or other imaging with no evidence of hepatocellular carcinoma (HCC), or alpha-fetoprotein of 21-50 ng/mL and computed tomography (CT)/magnetic resonance imaging (MRI) scan with no evidence of HCC, within 6 months of screening
Calculated creatinine clearance ≥ 50 mL/min
Negative human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis D virus (HDV) serologies
Less than 24 months of total prior adefovir dipivoxil exposure
Willing and able to provide written informed consent

You may not qualify if…

A participant who met any of the following exclusion criteria could not be enrolled in the study:
Pregnant women, women who were breastfeeding or who believed they may have wished to become pregnant during the course of the study
Males and females of reproductive potential who were unwilling to use an effective method of contraception during the study
Prior use of TDF or ETV
History of variceal bleeding, hepatorenal syndrome, Grade 3 or 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 60 days of screening
Grade 2 hepatic encephalopathy at screening
History of solid organ or bone marrow transplant
Current use of hepatotoxic drugs, nephrotoxic drugs, or drugs that interfere with renal tubular secretion
Current therapy with immunomodulators (eg, corticosteroids, interleukin-2, etc.) or investigational drugs
Diagnosis of proximal tubulopathy
Use of investigational agent within 30 days prior to screening
Known hypersensitivity to TDF, FTC, ETV, or formulation excipients of any of the study drug products

Where it is running

Pfleger Liver Institute — Los Angeles, California, United States
California Pacific Medical Center Research Institute — San Francisco, California, United States
University of Miami, Center for Liver Diseases — Miami, Florida, United States
Rush Presbyterian - St. Luke's Medical Center — Chicago, Illinois, United States
Henry Ford Hospital and Health System — Detroit, Michigan, United States
Mt. Sinai School of Medicine/ Mt. Sinai Medical Center — New York, New York, United States
Columbia Presbyterian Medical Center — New York, New York, United States
Metropolitan Research — Fairfax, Virginia, United States
Virginia Mason Medical Center — Seattle, Washington, United States
Heritage Medical Research Clinic — Calgary, Alberta, Canada
Vancouver General Hospital — Vancouver, British Columbia, Canada
The Gordon & Leslie Diamond Centre — Vancouver, British Columbia, Canada
Toronto General Hospital — Toronto, Ontario, Canada
Hopital Conception — Marseille, France
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie — Berlin, Germany
Universitat Heidelberg — Heidelberg, Germany
Johannes Gutenberg-Universitat — Mainz, Germany
General Hospital of Athens "Ippokratio" — Athens, Greece
Universita de Padova — Padova, Italy
Policlinico Universitario — Udine, Italy
Wojewodzki Szpital Specjalistyczny im Dluskeigo — Bialystok, Poland
Wojewodzki Szpital Obserwacy — Bydgoszcz, Poland
Wojewodzki Szpital Zakazny — Warsaw, Poland
National University Hospital Dept. of Gastroenterology & Hepatology — Singapore, Singapore
Singapore General Hospital — Singapore, Singapore

Full record on ClinicalTrials.gov

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