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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Gilead Sciences.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00116805
First received: June 30, 2005
Last updated: October 31, 2011
Last verified: October 2011

June 30, 2005
October 31, 2011
June 2005
June 2007   (final data collection date for primary outcome measure)
Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) <400 Copies/mL and Histological Improvement (2-point or Higher Reduction in the Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Complete response was a composite endpoint defined as histological response and HBV DNA below 400 copies/mL. Histological response was defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell scale consists of 5 domains, (Periportal +/- Bridging Necrosis [scored from best to worst 0, 1, 3, 4, 5, 6, or 10]; Intralobular Degeneration and Focal Necrosis [0 to 4]; Portal Inflammation [0 to 4]; and Fibrosis [0 to 4]). The necroinflammatory score is the combined score for necrosis + inflammation (0 [best] to 14 [worst]).
Not Provided
Complete list of historical versions of study NCT00116805 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Histological Response at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Histological response was defined as Knodell necroinflammatory score improvement of at least 2 points, without worsening in Knodell fibrosis score. The Knodell scale consists of 5 domains, (Periportal +/- Bridging Necrosis [scored from best to worst 0, 1, 3, 4, 5, 6, or 10]; Intralobular Degeneration and Focal Necrosis [0 to 4]; Portal Inflammation [0 to 4]; and Fibrosis [0 to 4]). The necroinflammatory score is the combined score for necrosis + inflammation (0 [best] to 14 [worst]).
  • Percentage of Participants With HBV DNA <400 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HBV DNA <400 Copies/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Normalized ALT was defined as ALT above the ULN at baseline and at or below the ULN at Week 96.
  • Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Normalized ALT was defined as ALT above the ULN at baseline and at or below the ULN at the end of blinded treatment.
  • Percentage of Participants With ALT Normalization at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Normalized ALT was defined as ALT above the ULN at baseline and at or below the ULN at Week 96.
  • Percentage of Participants With Hepatitis B E-antigen (HBeAg) Loss/Seroconversion at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Hepatitis B e-antigen (HBeAg) loss was defined as negative HBeAg result for those subjects with HBeAg-positive result at baseline. Seroconversion to anti-HBe was defined as HBeAg loss and positive anti-HBe result.
  • Percentage of Participants With HBeAg Loss or Seroconversion at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    HBeAg loss was defined as a negative HBeAg result for those participants with a positive HBeAg result at baseline. Seroconversion to anti-HBe was defined as HBeAg loss and positive anti-HBe result.
  • Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Hepatitis B s-antigen (HBsAg) loss was defined as negative HBsAg result for those participants with positive HBsAg result at baseline. Seroconversion to anti-HBs was defined as HBsAg loss and positive anti-HBs result.
  • Percentage of Participants With HBsAg Loss or Serconversion to Anti-HBs at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    HBsAg loss was defined as a negative HBsAg result for those participants with a positive HBsAg result at baseline. Seroconversion to anti-HBs was defined as HBsAg loss and positive anti-HBs result.
  • Percentage of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Participants evaluated for resistance included those with HBV DNA >/= 400 copies/mL at Week 96 in TDF monotherapy, those who discontinued after Week 48 with HBV DNA >/= 400 copies/mL, and those who added emtricitabine to their open-label TDF regimen and had HBV DNA >/= 400 copies/mL at the time of the addition.
Not Provided
Not Provided
Not Provided
 
A Study to Compare Tenofovir Versus Hepsera (Adefovir) for the Treatment of Hepatitis Be Antigen (HBeAg) Positive Chronic Hepatitis B
A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of HBeAg Positive Chronic Hepatitis B

This study is designed to evaluate the safety and antiviral activity of tenofovir disoproxil fumarate (TDF, tenofovir DF) compared to adefovir dipivoxil (ADV, Hepsera) for the treatment of HBeAg-positive chronic hepatitis B. Participants will receive either TDF or the approved hepatitis B therapy ADV. After 48 weeks all participants will be switched to open-label (OL) TDF.

Efficacy of TDF versus ADV 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. After 48 weeks, all participants will receive OL TDF, and the efficacy and safety of TDF will be monitored for an additional 336 weeks.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Chronic Hepatitis B
  • Drug: tenofovir disoproxil fumarate
    TDF 300 mg once daily for 48 weeks and then open-label TDF 300 mg once daily for an additional 336 weeks
    Other Name: Viread
  • Drug: adefovir dipivoxil
    ADV 10 mg once daily for 48 weeks and then open-label TDF 300 mg once daily for an additional 336 weeks
    Other Name: Hepsera (first 48 weeks) and then switch to Viread (additional 336 weeks)
  • Experimental: A
    Double-blind tenofovir disoproxil fumarate (TDF) 300 mg once daily and then switch to open-label (OL) TDF 300 mg once daily for an additional 336 weeks (TDF-TDF)
    Intervention: Drug: tenofovir disoproxil fumarate
  • Active Comparator: B
    Double-blind adefovir dipivoxil (ADV) 10 mg once daily and then switch to OL TDF 300 mg once daily for an additional 336 weeks (ADV-TDF)
    Intervention: Drug: adefovir dipivoxil

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
266
June 2014
June 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for participation in this study.

  • Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for more than 6 months.
  • 18 through 69 years of age, inclusive.
  • Active hepatitis B e-antigen (HBeAg) positive chronic HBV infection, with all of the following:

    • HBeAg positive at screening;
    • Alanine aminotransferase (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 (TDF or ADV) 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, prothrombin time (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 (TDF or ADV) 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 hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis delta 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.
Both
18 Years to 69 Years
No
Contact information is only displayed when the study is recruiting subjects
France,   United States,   Australia,   Bulgaria,   Canada,   Czech Republic,   United Kingdom,   Germany,   Greece,   Italy,   Netherlands,   New Zealand,   Poland,   Spain,   Turkey
 
NCT00116805
GS-US-174-0103
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Jeffrey D Bornstein, MD Gilead Sciences
Gilead Sciences
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP