A Study to Compare Tenofovir Versus Hepsera (Adefovir) for the Treatment of Hepatitis Be Antigen (HBeAg) Positive Chronic Hepatitis B
Information source: Gilead Sciences
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Hepatitis B
Intervention: tenofovir disoproxil fumarate (Drug); adefovir dipivoxil (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Gilead Sciences
Official(s) and/or principal investigator(s):
Elsa Mondou, MD, Study Chair, Affiliation: Gilead Sciences
This study is designed to evaluate the safety and antiviral activity of tenofovir compared to
Hepsera for the treatment of HBeAg positive chronic hepatitis B. Patients will either receive
tenofovir or the approved hepatitis B therapy, Hepsera.
Official title: A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of HBeAg Positive Chronic Hepatitis B
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: HBV DNA <400 copies/mL and histological improvement (at least a 2 point reduction in the Knodell necroinflammatory score without worsening in fibrosis)
HBV DNA <400 copies/mL
HBeAg and HBsAg loss/seroconversion
Development of resistance mutations
safety and tolerability
Efficacy of tenofovir versus Hepsera will be evaluated for histologic improvement, reductions
in serum 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.
Minimum age: 18 Years.
Maximum age: 69 Years.
A patient must meet all of the following inclusion criteria to be eligible for
participation in this study.
- Chronic HBV infection, defined as positive serum HBsAg for more than 6 months.
- 18 through 69 years of age, inclusive.
- Active HBeAg positive chronic HBV infection, with all of the following:
- HBeAg positive at screening;
- ALT levels > 2 × ULN and = 10 × 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, i. e., a Knodell fibrosis score equal to 4, will be
eligible for enrollment.
- Negative serum β-HCG
- Nucleotide naïve, i. e., no prior nucleotide (tenofovir DF or adefovir dipivoxil)
therapy for greater than 12 weeks.
- Nucleoside naïve, i. e., no prior nucleoside (any nucleoside) therapy for greater than
- 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.
A patient who meets any of the following exclusion criteria is not to be enrolled in this
- 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, PT > 1. 5 x
ULN, platelets < 75,000/mL, serum albumin < 3. 0 g/dL, or prior history of clinical
hepatic decompensation (e. g., ascites, jaundice, encephalopathy, variceal
- Received any nucleoside, nucleotide (tenofovir DF or adefovir dipivoxil) or interferon
(pegylated or not) therapy within 6 months prior to the pre-treatment biopsy.
- Evidence of hepatocellular carcinoma (HCC), i. e., α-fetoprotein >50 ng/mL.
- Coinfection with HCV, HIV, or HDV.
- Significant renal, cardiovascular, pulmonary, or neurological disease.
- Received solid organ or bone marrow transplantation.
- Is currently receiving therapy with immunomodulators (e. g., corticosteroids, etc.),
investigational agents, nephrotoxic agents, or agents susceptible of modifying renal
- Has proximal tubulopathy.
Locations and Contacts
Perth 6001, Australia
Varna 9010, Bulgaria
Sofia 1431, Bulgaria
Sofia 1233, Bulgaria
Hradec Kralove, Czech Republic
Prague, Czech Republic
Brno 62500, Czech Republic
Praha 6- Stresovice 169 02, Czech Republic
Nancy 54500, France
Clichy 92110, France
Lyon 69288, France
Grenoble 38043, France
Toulouse 31059, France
Strasbourg 67901, France
Paris 75651, France
Pessac 33600, France
Creteil 94010, France
Lille 59037, France
Duesseldorf 40237, Germany
Mainz 55131, Germany
Hannover 30623, Germany
Munchen 81377, Germany
Homburg/Saar 66421, Germany
Berlin 13353, Germany
Essen 45122, Germany
Koeln 50924, Germany
Dusseldorf 40225, Germany
Tubingen 72076, Germany
Frankfurt 60590, Germany
Kiel 24105, Germany
Herne 44623, Germany
Mannheim 68167, Germany
Berlin 10969, Germany
Athens 11526, Greece
Thessaloniki 54642, Greece
Thessaloniki 56429, Greece
Palermo 90127, Italy
Torino 10134, Italy
Rotterdam 3015, Netherlands
Auckland, New Zealand
Whakatane, New Zealand
Hamilton, New Zealand
Warszawa 01-201, Poland
Bydgoszcz 85-030, Poland
Krakow 31-501, Poland
Chorzow 41-500, Poland
Bialystok 15-540, Poland
Wroclaw 51-149, Poland
Lodz 91-437, Poland
Kielce 25-317, Poland
Barcelona 08035, Spain
Barcelona 08025, Spain
Madrid 28035, Spain
Santander 39008, Spain
Valencia 46009, Spain
Madrid 28007, Spain
Madrid 28006, Spain
Madrid 28034, Spain
Barcelona 08907, Spain
Istanbul 81324, Turkey
Ankara 06100, Turkey
London NW3 2QG, United Kingdom
Birmingham B15 2TH, United Kingdom
London WC1E 6HX, United Kingdom
Calgary, Alberta T2N4N1, Canada
Vancouver, British Columbia V5Z1H2, Canada
San Diego, California 92123, United States
San Diego, California 92115, United States
Los Angeles, California 90048, United States
Pasadena, California 91105, United States
San Jose, California 95116, United States
La Jolla, California 92067, United States
San Francisco, California 94115, United States
LaJolla, California 92067, United States
Orange, California 92868, United States
Miami, Florida 33136, United States
Cooper City, Florida 33026, United States
Atlanta, Georgia 30308, United States
Honolulu, Hawaii 96817, United States
Winnepeg, Manitoba R3E3P4, Canada
College Park, Maryland 20740, United States
Baltimore, Maryland 21229, United States
Boston, Massachusetts 02215, United States
Detroit, Michigan 48202, United States
Ann Arbor, Michigan 48109, United States
St. Louis, Missouri 63110, United States
Westmead, New South Wales 2145, Australia
Camperdown, New South Wales 2050, Australia
Concord, New South Wales 2139, Australia
Flushing, New York 11355, United States
New York, New York 10032, United States
Manhasset, New York 11030, United States
New York, New York 10029, United States
Bronx, New York 10467, United States
New York, New York 10021, United States
Toronto, Ontario M5T 2S8, Canada
Toronto, Ontario M5G 2C4, Canada
Ottawa, Ontario K1H 8L6, Canada
Herston, Queensland 4029, Australia
Memphis, Tennessee 38103, United States
Houston, Texas 77005, United States
San Antonio, Texas 78229, United States
Heidelberg, Victoria 3084, Australia
Melbourne, Victoria 3004, Australia
Footscray, Victoria 3011, Australia
Richmond, Virginia 23249, United States
Annandale, Virginia 22003, United States
Fairfax, Virginia 22031, United States
Seattle, Washington 98104, United States
Starting date: May 2005
Ending date: June 2011
Last updated: January 31, 2008