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

NCT ID: NCT00307489

Last Updated: 2011-11-01

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2010-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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1

TDF

Group Type EXPERIMENTAL

tenofovir DF

Intervention Type DRUG

300 mg tablet, once daily (QD)

2

FTC/TDF

Group Type EXPERIMENTAL

emtricitabine /tenofovir DF

Intervention Type DRUG

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

Interventions

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emtricitabine /tenofovir DF

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

Intervention Type DRUG

tenofovir DF

300 mg tablet, once daily (QD)

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen J Rossi, PharmD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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San Francisco, California, United States

Site Status

San Jose, California, United States

Site Status

Flushing, New York, United States

Site Status

New York, New York, United States

Site Status

New York, New York, United States

Site Status

New York, New York, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Fairfax, Virginia, United States

Site Status

Norfolk, Virginia, United States

Site Status

Richmond, Virginia, United States

Site Status

Angers, , France

Site Status

Clichy, , France

Site Status

Lille, , France

Site Status

Lyon, , France

Site Status

Marseille, , France

Site Status

Rouen, , France

Site Status

Strasbourg, , France

Site Status

Berlin, , Germany

Site Status

Berlin, , Germany

Site Status

Bonn, , Germany

Site Status

Erlangen, , Germany

Site Status

Essen, , Germany

Site Status

Frankfurt, , Germany

Site Status

Hamburg, , Germany

Site Status

Hanover, , Germany

Site Status

Herne, , Germany

Site Status

München, , Germany

Site Status

Seville, , Spain

Site Status

Countries

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United States France Germany Spain

References

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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.

Reference Type RESULT
PMID: 16871563 (View on PubMed)

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.

Reference Type RESULT
PMID: 19052126 (View on PubMed)

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.

Reference Type RESULT
PMID: 18191272 (View on PubMed)

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.

Reference Type RESULT
PMID: 18199519 (View on PubMed)

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.

Reference Type RESULT
PMID: 19998272 (View on PubMed)

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.

Reference Type RESULT
PMID: 20600025 (View on PubMed)

Other Identifiers

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GS-US-174-0106

Identifier Type: -

Identifier Source: org_study_id