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.

Condition	Intervention	Phase
Chronic Hepatitis B	Drug: tenofovir disoproxil fumarate 300 mg once daily  Drug: adefovir dipivoxil 10 mg once daily	Phase III

Further Study Details: 

Expected Total Enrollment:  240

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.

Ages Eligible for Study:  18 Years   -   69 Years,  Genders Eligible for Study:  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 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 12 weeks.
• 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:

A patient who meets any of the following exclusion criteria is not to be enrolled in this study.

• 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 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), 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 excretion.
• Has proximal tubulopathy.

Please refer to this study by ClinicalTrials.gov identifier  NCT00116805

Cary Moxham, PhD      919-493-5980  Ext. 7102    cary.moxham@gilead.com

California
      San Diego,  California,  92123,  United States; Recruiting
      Orange,  California,  92868,  United States; Not yet recruiting
      San Diego,  California,  92115,  United States; Not yet recruiting
      Los Angeles,  California,  90048,  United States; Not yet recruiting
      Pasadena,  California,  91105,  United States; Not yet recruiting
      San Jose,  California,  95116,  United States; Not yet recruiting
      La Jolla,  California,  92067,  United States; Not yet recruiting
Florida
      Miami,  Florida,  33136,  United States; Recruiting
      Hollywood,  Florida,  33021,  United States; Not yet recruiting
Georgia
      Atlanta,  Georgia,  30308,  United States; Recruiting
Hawaii
      Honolulu,  Hawaii,  96817,  United States; Recruiting
Louisiana
      New Orleans,  Louisiana,  70115,  United States; Not yet recruiting
Maryland
      College Park,  Maryland,  20740,  United States; Recruiting
Massachusetts
      Boston,  Massachusetts,  02215,  United States; Not yet recruiting
Michigan
      Detroit,  Michigan,  48202,  United States; Recruiting
      Ann Arbor,  Michigan,  48109,  United States; Not yet recruiting
Missouri
      St. Louis,  Missouri,  63110,  United States; Not yet recruiting
New York
      Flushing,  New York,  11355,  United States; Recruiting
      New York,  New York,  10032,  United States; Recruiting
      New York,  New York,  10021,  United States; Not yet recruiting
      Manhasset,  New York,  11030,  United States; Recruiting
      New York,  New York,  10029,  United States; Not yet recruiting
      New York,  New York,  10013,  United States; Not yet recruiting
Tennessee
      Memphis,  Tennessee,  38103,  United States; Not yet recruiting
Virginia
      Richmond,  Virginia,  23249,  United States; Recruiting
      Annandale,  Virginia,  22003,  United States; Recruiting
Washington
      Seattle,  Washington,  98195,  United States; Not yet recruiting
      Seattle,  Washington,  98104,  United States; Not yet recruiting

Study chairs or principal investigators

Herve Mommeja-Marin, MD,  Study Chair,  Gilead Sciences   

Study ID Numbers:  GS-US-174-0103
Record last reviewed:  June 2005
Last Updated:  June 30, 2005
Record first received:  June 30, 2005
ClinicalTrials.gov Identifier:  NCT00116805
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-05