NCT00307489

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
106

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Mar 2006

Typical duration for phase_2

Geographic Reach
4 countries

28 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2006

Completed
23 days until next milestone

First Submitted

Initial submission to the registry

March 24, 2006

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 28, 2006

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2008

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

July 7, 2009

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2010

Completed
Last Updated

November 1, 2011

Status Verified

October 1, 2011

Enrollment Period

1.8 years

First QC Date

March 24, 2006

Results QC Date

January 30, 2009

Last Update Submit

October 4, 2011

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (2)

  • Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48

    48 weeks

  • Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48

    48 Weeks

Secondary Outcomes (17)

  • Change From Baseline in log10 Plasma HBV DNA Levels at Week 48

    48 Weeks

  • Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 48

    48 Weeks

  • Percentage of Participants With Normal ALT at Week 48

    48 Weeks

  • Percentage of Participants With Normalized ALT at Week 48

    48 Weeks

  • Hepatitis B Early Antigen (HBeAg) Loss at Week 48

    48 Weeks

  • +12 more secondary outcomes

Study Arms (2)

1

EXPERIMENTAL

TDF

Drug: tenofovir DF

2

EXPERIMENTAL

FTC/TDF

Drug: emtricitabine /tenofovir DF

Interventions

tenofovir DFDRUG

300 mg tablet, once daily (QD)

1
emtricitabine /tenofovir DFDRUG

emtricitabine 200 mg/tenofovir DF 300 mg once daily (combination tablet)

2

Eligibility Criteria

Age18 Years - 69 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • Currently treated with adefovir dipivoxil 10 mg QD (for at least 24 weeks but not more than 96 weeks)
  • HBeAg positive or negative at screening
  • Plasma HBV DNA \>/= 1000 copies/mL at screening (irrespective of HBeAg status)
  • Serum ALT less than 10 times the upper limit of normal (ULN)
  • Calculated creatinine clearance of at least 70 mL/min using the Cockcroft-Gault formula
  • Hemoglobin at least 8 g/dL
  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

Unknown Facility

San Francisco, California, 94115, United States

Location

Unknown Facility

San Jose, California, 95128, United States

Location

Unknown Facility

Flushing, New York, 11355, United States

Location

Unknown Facility

New York, New York, 10013, United States

Location

Unknown Facility

New York, New York, 10016, United States

Location

Unknown Facility

New York, New York, 10021, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19107, United States

Location

Unknown Facility

Fairfax, Virginia, 22031, United States

Location

Unknown Facility

Norfolk, Virginia, 23502, United States

Location

Unknown Facility

Richmond, Virginia, 23249, United States

Location

Unknown Facility

Angers, 49933, France

Location

Unknown Facility

Clichy, 92110, France

Location

Unknown Facility

Lille, 59037, France

Location

Unknown Facility

Lyon, 69288, France

Location

Unknown Facility

Marseille, 13285, France

Location

Unknown Facility

Rouen, 76031, France

Location

Unknown Facility

Strasbourg, 67091, France

Location

Unknown Facility

Berlin, 10969, Germany

Location

Unknown Facility

Berlin, 13353, Germany

Location

Unknown Facility

Bonn, 53105, Germany

Location

Unknown Facility

Erlangen, 91054, Germany

Location

Unknown Facility

Essen, 45122, Germany

Location

Unknown Facility

Frankfurt, 60590, Germany

Location

Unknown Facility

Hamburg, 20999, Germany

Location

Unknown Facility

Hanover, 30623, Germany

Location

Unknown Facility

Herne, 44623, Germany

Location

Unknown Facility

München, 81377, Germany

Location

Unknown Facility

Seville, 41014, Spain

Location

Related Publications (6)

  • van Bommel F, Zollner B, Sarrazin C, Spengler U, Huppe D, Moller B, Feucht HH, Wiedenmann B, Berg T. Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy. Hepatology. 2006 Aug;44(2):318-25. doi: 10.1002/hep.21253.

    PMID: 16871563RESULT

  • Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Washington MK, Sorbel J, Anderson J, Snow-Lampart A, Mondou E, Quinn J, Rousseau F. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008 Dec 4;359(23):2442-55. doi: 10.1056/NEJMoa0802878.

    PMID: 19052126RESULT

  • Reijnders JG, Janssen HL. Potency of tenofovir in chronic hepatitis B: mono or combination therapy? J Hepatol. 2008 Mar;48(3):383-6. doi: 10.1016/j.jhep.2007.12.006. Epub 2007 Dec 31. No abstract available.

    PMID: 18191272RESULT

  • Tan J, Degertekin B, Wong SN, Husain M, Oberhelman K, Lok AS. Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovir-resistant mutations. J Hepatol. 2008 Mar;48(3):391-8. doi: 10.1016/j.jhep.2007.09.020. Epub 2008 Jan 3.

    PMID: 18199519RESULT

  • van Bommel F, de Man RA, Wedemeyer H, Deterding K, Petersen J, Buggisch P, Erhardt A, Huppe D, Stein K, Trojan J, Sarrazin C, Bocher WO, Spengler U, Wasmuth HE, Reinders JG, Moller B, Rhode P, Feucht HH, Wiedenmann B, Berg T. Long-term efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues. Hepatology. 2010 Jan;51(1):73-80. doi: 10.1002/hep.23246.

    PMID: 19998272RESULT

  • Berg T, Marcellin P, Zoulim F, Moller B, Trinh H, Chan S, Suarez E, Lavocat F, Snow-Lampart A, Frederick D, Sorbel J, Borroto-Esoda K, Oldach D, Rousseau F. Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection. Gastroenterology. 2010 Oct;139(4):1207-17. doi: 10.1053/j.gastro.2010.06.053. Epub 2010 Jun 20.

    PMID: 20600025RESULT

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

TenofovirEmtricitabine

Condition Hierarchy (Ancestors)

Hepatitis BBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

OrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The randomized and treated (RAT) analysis set includes all subjects who were ongoing at the time of analysis (i.e., those on blinded therapy and those who switched to open-label FTC/TDFdue to persistent viremia).

Results Point of Contact

Title
Stephen J. Rossi, PharmD
Organization
Gilead Sciences, Inc.
stephen.rossi@gilead.com
650-522-4212

Study Officials

  • Stephen J Rossi, PharmD

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 24, 2006

First Posted

March 28, 2006

Study Start

March 1, 2006

Primary Completion

January 1, 2008

Study Completion

October 1, 2010

Last Updated

November 1, 2011

Results First Posted

July 7, 2009

Record last verified: 2011-10

Locations

FR(7)ES(1)DE(10)US(10)