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Chronic Hepatitis BPhase 2NCT00307489

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

A Phase 2 study testing tenofovir DF and emtricitabine /tenofovir DF in people with Chronic Hepatitis B, run by Gilead Sciences at 28 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 69 years
Conditions the study is for
Chronic Hepatitis B
What is being tested?
tenofovir DF and emtricitabine /tenofovir DF
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
106 participants
Where
28 sitesin 4 countries
Study dates
Mar 2006to Oct 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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)
Show all 14Show fewer
  • 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

Who cannot join

  • 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.
Show all 12Show fewer
  • 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

Trial locations and contacts

28 sites in 4 countries.

28 sites in 4 countries

United States10 sites

  • Study site

    Fairfax, Virginia, 22031

  • Study site

    Flushing, New York, 11355

  • Study site

    New York, New York, 10013

  • Study site

    New York, New York, 10016

  • Study site

    New York, New York, 10021

  • Study site

    Norfolk, Virginia, 23502

  • Study site

    Philadelphia, Pennsylvania, 19107

  • Study site

    Richmond, Virginia, 23249

  • Study site

    San Francisco, California, 94115

  • Study site

    San Jose, California, 95128

Other trials in United States

Germany10 sites

  • Study site

    Berlin, 10969

  • Study site

    Berlin, 13353

  • Study site

    Bonn, 53105

  • Study site

    Erlangen, 91054

  • Study site

    Essen, 45122

  • Study site

    Frankfurt, 60590

  • Study site

    Hamburg, 20999

  • Study site

    Hanover, 30623

  • Study site

    Herne, 44623

  • Study site

    München, 81377

Other trials in Germany

France7 sites

  • Study site

    Angers, 49933

  • Study site

    Clichy, 92110

  • Study site

    Lille, 59037

  • Study site

    Lyon, 69288

  • Study site

    Marseille, 13285

  • Study site

    Rouen, 76031

  • Study site

    Strasbourg, 67091

Other trials in France

Spain1 site

  • Study site

    Seville, 41014

Other trials in Spain

About this study

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

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.

Being tested
tenofovir DF, emtricitabine /tenofovir DF
Medical subject headings
Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tenofovir DFDrug

    300 mg tablet, once daily (QD)

  • emtricitabine /tenofovir DFDrug

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

Study groups in NCT00307489
Study groupRoleWhat they receive
1ExperimentalTDF
Receives: Drug: tenofovir DF
2ExperimentalFTC/TDF
Receives: Drug: emtricitabine /tenofovir DF

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 48 weeks

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

    Measured: 48 Weeks

Secondary outcomes (17)

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

    Measured: 48 Weeks

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

    Measured: 48 Weeks

  3. Percentage of Participants With Normal ALT at Week 48

    ULN for males = 43 U/L; 34 U/L for females

    Measured: 48 Weeks

  4. Percentage of Participants With Normalized ALT at Week 48

    Subjects with elevated ALT at baseline that return to normal by Week 48.

    Measured: 48 Weeks

  5. Hepatitis B Early Antigen (HBeAg) Loss at Week 48

    Defined as having negative serum HBeAg for subjects with positive HBeAg at baseline.

    Measured: 48 Weeks

  6. HBeAg Seroconversion at Week 48

    Defined as having negative serum HBeAg and positive serum antibody to HBeAg [anti-HBe] for subjects with positive serum HBeAg at baseline.

    Measured: 48 Weeks

  7. HBsAg Loss at Week 48

    Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.

    Measured: 48 Weeks

  8. Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 48

    Defined as having negative serum HBsAg and positive serum antibody to HBsAg [anti-HBs] for subject with positive serum HBsAg at baseline.

    Measured: 48 Weeks

  9. Change From Baseline in log10 Plasma HBV DNA Levels at Week 168

    Measured: 168 weeks

  10. Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 168

    Measured: 168 weeks

  11. Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168

    Measured: 168 weeks

  12. Percentage of Participants With Normal ALT at Week 168

    ULN for males = 43 U/L; ULN for females = 34 U/L

    Measured: 168 weeks

  13. Percentage of Participants With Normalized ALT at Week 168

    Subjects with elevated ALT at baseline that return to normal by Week 48.

    Measured: 168 weeks

  14. Hepatitis B Early Antigen (HBeAg) Loss at Week 168

    Defined as having negative serum HBeAg for subjecst with positive HBeAg at baseline.

    Measured: 168 weeks

  15. Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 168

    Defined as having negative serum BHsAg and positive serum antibody to HBsAg (anti-HBs) for subject with positive serum BHsAg at baseline.

    Measured: 168 weeks

  16. HBsAg Loss at Week 168

    Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.

    Measured: 168 weeks

  17. Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 168

    P-values were from a Cochran-Mantel-Haenszel test, controlling for baseline HBeAg status and prior lamivudine use.

    Measured: 168 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2006 (estimated)
  2. Study startMar 2006
  3. Primary completionJan 2008
  4. Study completionOct 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
106 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00307489
Sponsor's protocol ID
GS-US-174-0106
Status last verified
Oct 2011
First submitted
24 Mar 2006
Last updated
1 Nov 2011
Data monitoring committee
No

Publications

  • 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.

    PubMed 16871563

  • 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.

    PubMed 19052126

  • 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.

    PubMed 18191272

  • 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.

    PubMed 18199519

  • 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.

    PubMed 19998272

  • 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.

    PubMed 20600025

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing tenofovir DF and emtricitabine /tenofovir DF in people with Chronic Hepatitis B, run by Gilead Sciences at 28 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States, Germany, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48 (time frame: 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00307489, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2011.

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