Skip to main content
OpenTrials
Completed

NCT Number: NCT00507507

A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)

The main objective of the study was to evaluate the antiviral activity of tenofovir disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the immune tolerant phase of HBV infection.

The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy was evaluated for suppression of the virus (decrease in HBV DNA), serological response (generation of antibodies to the virus), biochemical response (changes in liver enzymes), and the development of drug-resistant mutations. The safety and tolerability of both tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for adverse events and changes in laboratory parameters.

Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus tenofovir DF. All subjects were to continue on blinded study medication until the last subject reached Week 192. Participants who permanently discontinued study drug (on or before Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject reached Week 192.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Chronic Hepatitis B Blood-Borne Infections Chronic Disease Communicable Diseases DNA Virus Infections Digestive System Diseases Disease Attributes Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis B, Chronic Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Virus Diseases

Age range

18 year–69 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Camperdown, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive > 3 months and positive for immunoglobulin G antibody against hepatitis B core antigen
  • 18 through 69 years of age, inclusive
  • Hepatitis B e antigen (HBeAg) positive
  • HBV DNA ≥ 10^8 copies/mL
  • ALT ≤ the upper limit of the normal range (ULN)
  • Willing and able to provide written informed consent
  • Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)
  • Calculated creatinine clearance ≥ 70 mL/min
  • Hemoglobin ≥ 10 g/dL
  • Neutrophils ≥ 1,500/mm^3
  • No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)

Exclusion criteria

  • Pregnant women, women who were breast feeding, or who believed they may have wished to become pregnant during the course of the study
  • Males and females of reproductive potential unwilling to use an effective method of contraception during the study
  • Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, prothrombin time > 1.2 x ULN, platelets < 150,000/mm^3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, or variceal hemorrhage)
  • Received interferon (pegylated or not) therapy within 6 months of the screening visit
  • Alpha-fetoprotein > 50 ng/mL
  • Evidence of hepatocellular carcinoma
  • Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus
  • Significant renal, cardiovascular, pulmonary, or neurological disease
  • Received solid organ or bone marrow transplantation
  • Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
  • Had proximal tubulopathy
  • Known hypersensitivity to the study drugs, the metabolites, or formulation excipients

Treatment and study plan

Tenofovir DF

Drug

Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily

Other names: Viread®

FTC

Drug

Emtricitabine (FTC) 200 mg capsule taken orally once daily

Other names: Emtriva®

Placebo

Drug

Placebo to match FTC taken once daily

Primary outcomes

  1. Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192

    Time frame: Week 192

    The percentage of participants with HBV DNA < 400 copies/mL at Week 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.

Secondary outcomes

  1. Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144

    Time frame: Weeks 48, 96, and 144

    The percentage of participants with HBV DNA < 400 copies/mL at Weeks 48, 96, and 144 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.

  2. Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192

    Time frame: Weeks 48, 96, 144, and 192

    The percentage of participants with HBV DNA < 169 copies/mL at Weeks 48, 96, 144, and 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.

  3. Change From Baseline in HBV DNA at Week 48

    Time frame: Baseline to Week 48

    The change from baseline in HBV DNA at Week 48 was analyzed.

  4. Change From Baseline in HBV DNA at Week 96

    Time frame: Baseline to Week 96

    The change from baseline in HBV DNA at Week 96 was analyzed.

  5. Change From Baseline in HBV DNA at Week 144

    Time frame: Baseline to Week 144

    The change from baseline in HBV DNA at Week 144 was analyzed.

  6. Change From Baseline in HBV DNA at Week 192

    Time frame: Baseline to Week 192

    The change from baseline in HBV DNA at Week 192 was analyzed.

  7. Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192

    Time frame: Weeks 48, 96, 144, and 192

    Range of normal ALT was 6 to 34 U/L for females, 6 to 43 U/L for males. Participants with missing data were considered to have failed to achieve the criteria for evaluation.

  8. Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192

    Time frame: Weeks 48, 96, 144, and 192

    The number of participants with HBeAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative.

    No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.

  9. Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192

    Time frame: Weeks 48, 96, 144, and 192

    The number of participants with seroconversion to anti-HBe at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive.

    No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.

  10. Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192

    Time frame: Weeks 48, 96, 144, and 192

    The number of participants with HBsAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.

  11. Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192

    Time frame: Weeks 48, 96, 144, and 192

    The number of participants with seroconversion to anti-HBs at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.

  12. Occurrence of HBV Resistance Mutations

    Time frame: Baseline to Week 192

    The development of HBV resistance mutations (occurrence of conserved site changes and/or polymorphic site changes) was analyzed for the overall study period (through Week 192).

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study title

A Randomized, Double-Blind Study Evaluating Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus the Combination of Emtricitabine and Tenofovir DF for the Treatment of Chronic Hepatitis B

Important dates

Study start
2007
Primary completion
2012
Study completion
2012
First posted
Jul 26, 2007
Registry last updated
Jul 17, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.