A Study to Compare Tenofovir Versus Hepsera (Adefovir) for the Treatment of HBeAg Negative Chronic Hepatitis B

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, M.D., Study Chair, Affiliation: Gilead Sciences

This study is designed to evaluate the safety and antiviral activity of tenofovir disoproxil fumarate (DF) compared to Hepsera for the treatment of HBeAg negative 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 Presumed Pre-Core Mutant Chronic Hepatitis B

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Primary outcome: HBV DNA <400 copies/mL and Histological Improvement (2 point reduction in Knodell Necroinflammatory score without worsening in Knodell fibrosis score)

Secondary outcome:

HBV DNA <400 copies/mL

Histological Improvement

Development of resistance mutations

Safety and Tolerability

ALT normalization

Detailed description: The efficacy of tenofovir versus Hepsera will be evaluated for histologic improvement, reductions in serum hepatitis B virus (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. Gender(s): Both.

Criteria:

Inclusion Criteria:

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 at least 6 months.

- 18 through 69 years of age, inclusive.

- Active HBeAg negative chronic HBV infection, with all of the following:

- HBeAg negative and HBeAb positive at screening;

- ALT levels > ULN and

- serum HBV DNA > 100,000 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

120 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

12 weeks. However, up to 120 patients with greater than 12 weeks prior lamivudine experience will be eligible.

- 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

Exclusion Criteria:

- Pregnant women, women who are breast feeding, or women 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.

- 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 hemorrhage)

- 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)

- 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

- Is currently receiving therapy with immunomodulators (e. g., corticosteroids, etc.),

investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion

- Has proximal tubulopathy

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, 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

Hamburg 20251, 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, 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

Wroclaw 51-149, Poland

Bialystok 15-540, Poland

Lodz 91-437, Poland

Kielce 25-317, Poland

Barcelona 08035, Spain

Barcelona 08025, Spain

Madrid 28035, Spain

Santander 39008, Spain

Madrid 28007, Spain

Valencia 46009, Spain

Madrid 28006, Spain

Madrid 28034, Spain

Barcelona 08907, Spain

Izmir, Turkey

Bursa, Turkey

Istanbul, Turkey

Istanbul 81324, Turkey

Ankara 06100, Turkey

London NW3 2QG, United Kingdom

Birmingham B15 2TH, United Kingdom

London WC1E 6HX, United Kingdom

Calgary, Alberta T2N 4N1, Canada

Vancouver, British Columbia V5Z1H2, Canada

San Diego, California 92123, United States

San Diego, California 92115, United States

La Jolla, California 92067, United States

Los Angeles, California 90048, United States

Pasadena, California 91105, United States

San Jose, California 95116, United States

San Francisco, California 94115, 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

Winnipeg, Manitoba R3E3P4, Canada

College Park, Maryland 20740, United States

Baltimore, Maryland 21229, 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: June 2005
Ending date: May 2010
Last updated: December 22, 2007