Treatment of Persistent Viremia (Virus in Blood) in Chronic Hepatitis B Subjects Already Receiving Adefovir Dipivoxil

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00307489
First received: March 24, 2006
Last updated: October 4, 2011
Last verified: October 2011
  Purpose

This study explores the efficacy, safety and tolerability of tenofovir DF (TDF) 300 mg once daily monotherapy versus the combination of emtricitabine 200 mg plus tenofovir DF 300 mg (FTC/TDF) once daily in subjects currently being treated with adefovir dipivoxil (Hepsera) for chronic hepatitis B who have persistent viral replication (detectable hepatitis B virus deoxyribonucleic acid [HBV DNA]).

Subjects with confirmed (within 4 weeks) plasma HBV DNA ≥ 400 copies/mL during double blind treatment at Week 24 or any time thereafter have the option of receiving 12 weeks of open-label FTC/TDF which may be continued through the end of the 168-week treatment period if there is a virologic response (HBV DNA < 400 copies/mL). Alternatively, subjects with confirmed HBV DNA < 400 copies/mL at or any time after Week 24 of double-blind treatment may continue blinded therapy up to Week 168 at the discretion of the investigator. If, in the investigator's opinion, it is felt that continued blinded treatment beyond 24 weeks in subjects with confirmed HBV DNA ≥ 400 copies/mL is not beneficial, the subject may discontinue the study and begin commercially available HBV therapy rather than initiate open-label FTC/TDF.


Condition Intervention Phase
Chronic Hepatitis B
Drug: tenofovir DF
Drug: emtricitabine /tenofovir DF
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind Study Exploring the Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects Currently Being Treated With Adefovir Dipivoxil for Chronic Hepatitis B and Having Persistent Viral Replication

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in log10 Plasma HBV DNA Levels at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Normal ALT at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    ULN for males = 43 U/L; 34 U/L for females

  • Percentage of Participants With Normalized ALT at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Subjects with elevated ALT at baseline that return to normal by Week 48.

  • Hepatitis B Early Antigen (HBeAg) Loss at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Defined as having negative serum HBeAg for subjects with positive HBeAg at baseline.

  • HBeAg Seroconversion at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Defined as having negative serum HBeAg and positive serum antibody to HBeAg [anti-HBe] for subjects with positive serum HBeAg at baseline.

  • HBsAg Loss at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.

  • Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Defined as having negative serum HBsAg and positive serum antibody to HBsAg [anti-HBs] for subject with positive serum HBsAg at baseline.

  • Change From Baseline in log10 Plasma HBV DNA Levels at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Normal ALT at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
    ULN for males = 43 U/L; ULN for females = 34 U/L

  • Percentage of Participants With Normalized ALT at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
    Subjects with elevated ALT at baseline that return to normal by Week 48.

  • Hepatitis B Early Antigen (HBeAg) Loss at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
    Defined as having negative serum HBeAg for subjecst with positive HBeAg at baseline.

  • Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
    Defined as having negative serum BHsAg and positive serum antibody to HBsAg (anti-HBs) for subject with positive serum BHsAg at baseline.

  • HBsAg Loss at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
    Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.

  • Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 168 [ Time Frame: 168 weeks ] [ Designated as safety issue: No ]
    P-values were from a Cochran-Mantel-Haenszel test, controlling for baseline HBeAg status and prior lamivudine use.


Enrollment: 106
Study Start Date: March 2006
Study Completion Date: October 2010
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
TDF
Drug: tenofovir DF
300 mg tablet, once daily (QD)
Experimental: 2
FTC/TDF
Drug: emtricitabine /tenofovir DF
emtricitabine 200 mg/tenofovir DF 300 mg once daily (combination tablet)

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 through 69 years of age, inclusive
  • Chronic HBV infection, defined as positive serum HBsAg for at least 6 months
  • Active chronic HBV infection with all the following:

    1. Currently treated with adefovir dipivoxil 10 mg QD (for at least 24 weeks but not more than 96 weeks)
    2. HBeAg positive or negative at screening
    3. Plasma HBV DNA >/= 1000 copies/mL at screening (irrespective of HBeAg status)
    4. Serum ALT less than 10 times the upper limit of normal (ULN)
    5. Calculated creatinine clearance of at least 70 mL/min using the Cockcroft-Gault formula
    6. Hemoglobin at least 8 g/dL
    7. Neutrophils at least 1,000 /mm3
  • Nucleoside naive except for lamivudine (>/= 12 weeks of therapy)
  • Negative serum beta human chorionic gonadotropin
  • Compliant with adefovir dipivoxil
  • Willing and able to provide written informed consent

Exclusion Criteria:

  • Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
  • Male or females of reproductive potential who are unwilling to use an effective method of contraceptive while enrolled in 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 greater than 1.5 times ULN, prothrombin time (PT) greater than 1.5 times ULN, platelets less than 75,000/mm3, serum albumin less than 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)
  • Prior use of tenofovir DF or entecavir
  • Received treatment with interferon or pegylated interferon within 6 months of the screening visit
  • Evidence of hepatocellular carcinoma (HCC); for example, alpha-fetoprotein greater than 50 ng/mL or by any other standard of care measure.
  • Co-infection with HCV (based on serology), 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 (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion
  • Has proximal tubulopathy
  • Known hypersensitivity to the study drugs (tenofovir DF or emtricitabine/tenofovir DF), the metabolites (tenofovir or emtricitabine) or formulation excipients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00307489

Locations
United States, California
San Francisco, California, United States, 94115
San Jose, California, United States, 95128
United States, New York
Flushing, New York, United States, 11355
New York, New York, United States, 10016
New York, New York, United States, 10021
New York, New York, United States, 10013
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
United States, Virginia
Fairfax, Virginia, United States, 22031
Norfolk, Virginia, United States, 23502
Richmond, Virginia, United States, 23249
France
Angers, France, 49933
Clichy, France, 92110
Lille, France, 59037
Lyon, France, 69288
Marseille, France, 13285
Rouen, France, 76031
Strasbourg, France, 67091
Germany
Berlin, Germany, 13353
Berlin, Germany, 10969
Bonn, Germany, 53105
Erlangen, Germany, 91054
Essen, Germany, 45122
Frankfurt, Germany, 60590
Hamburg, Germany, 20999
Hannover, Germany, 30623
Herne, Germany, 44623
Munchen, Germany, 81377
Spain
Sevilla, Spain, 41014
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Stephen J Rossi, PharmD Gilead Sciences
  More Information

Publications:

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00307489     History of Changes
Other Study ID Numbers: GS-US-174-0106
Study First Received: March 24, 2006
Results First Received: January 30, 2009
Last Updated: October 4, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Adefovir
Adefovir dipivoxil
Tenofovir
Tenofovir disoproxil
Emtricitabine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 24, 2014