A Study to Compare Tenofovir Versus Hepsera (Adefovir) for the Treatment of HBeAg Negative Chronic Hepatitis B - Full Text View

Sponsor:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00117676

Purpose

This study is designed to evaluate the safety and antiviral activity of tenofovir disoproxil fumarate (DF) compared to Hepsera for 48 weeks for the treatment of HBeAg negative chronic hepatitis B. Patients will either receive tenofovir or the approved hepatitis B therapy, Hepsera for 48 weeks. After 48 weeks all patients will be switched to open label tenofovir.

Condition	Intervention	Phase
Chronic Hepatitis B	Drug: tenofovir disoproxil fumarate Drug: adefovir dipivoxil	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of Presumed Pre-Core Mutant Chronic Hepatitis B

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis B

Drug Information available for: Adefovir Adefovir dipivoxil Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Hepatitis B Vaccines

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

HBV DNA <400 copies/mL and Histological Improvement (2 point reduction in Knodell Necroinflammatory score without worsening in Knodell fibrosis score) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

HBV DNA <400 copies/mL [ Time Frame: 48 weeks and then annually through 384 weeks ] [ Designated as safety issue: No ]
Histological Improvement [ Time Frame: 48 weeks and 240 weeks ] [ Designated as safety issue: No ]
Development of resistance mutations [ Time Frame: 48 weeks and then annually through 384 weeks ] [ Designated as safety issue: No ]
Safety and Tolerability [ Time Frame: 48 weeks and then annually through 384 weeks ] [ Designated as safety issue: Yes ]
ALT normalization [ Time Frame: 48 weeks and then annually through 384 weeks ] [ Designated as safety issue: No ]

Enrollment:	375
Study Start Date:	June 2005
Estimated Study Completion Date:	May 2014
Primary Completion Date:	May 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Double blind tenofovir disoproxil fumarate 300 mg once daily for 48 weeks then switch to open label tenofovir disoproxil fumarate 300 mg once daily for an additional 336 weeks	Drug: tenofovir disoproxil fumarate double blind tenofovir disoproxil fumarate 300 mg once daily for 48 weeks then open label tenofovir disoproxil fumarate 300 mg daily for an additional 336 weeks
B: Active Comparator Double blind adefovir dipivoxil 10 mg once daily for 48 weeks then switch to tenofovir disoproxil fumarate 300 mg once daily for an additional 336 weeks	Drug: adefovir dipivoxil Adefovir dipivoxil 10 mg once daily for 48 weeks then switch to open label tenofovir disoproxil fumarate for an additional 336 weeks

Detailed Description:

The efficacy of tenofovir versus Hepsera will be evaluated for histologic improvement, reductions in serum hepatitis B virus (HBV) DNA, changes in liver enzymes, and the generation of antibody to the virus. Safety will be assessed by evaluating adverse events, laboratory abnormalities and the development of drug-resistant mutations. After 48 weeks all patients will receive tenofovir and the efficacy and safety of tenofovir will continue to be monitored for an additional 336 weeks.

Eligibility

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

Criteria

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for participation in this study:

Chronic HBV infection, defined as positive serum HBsAg for at least 6 months.
18 through 69 years of age, inclusive.
Active HBeAg negative chronic HBV infection, with all of the following:
- HBeAg negative and HBeAb positive at screening;
- ALT levels > ULN and </= 10 x ULN;
- serum HBV DNA > 100,000 copies/mL at screening;
- creatinine clearance >/= 70 mL/min;
- hemoglobin >/= 8 g/dL;
- neutrophils >/= 1,000 /mL.
Knodell necroinflammatory score >/= 3 and a Knodell fibrosis score < 4. However, up to 120 patients with cirrhosis, i.e., a Knodell fibrosis score equal to 4, will be eligible for enrollment.
Negative serum β-HCG
Nucleotide naïve, i.e., no prior nucleotide (tenofovir DF or adefovir dipivoxil) therapy for greater than 12 weeks.
Nucleoside naïve, i.e., no prior nucleoside (any nucleoside) therapy for greater than 12 weeks. However, up to 120 patients with greater than 12 weeks prior lamivudine experience will be eligible.
Willing and able to provide written informed consent.
Had a liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline

Exclusion Criteria:

Pregnant women, women who are breast feeding, or women who believe they may wish to become pregnant during the course of the study
Males and females of reproductive potential who are unwilling to use an "effective" method of contraception during the study.
Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, PT > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage)
Received any nucleoside, nucleotide (tenofovir DF or adefovir dipivoxil) or interferon (pegylated or not) therapy within 6 months prior to the pre treatment biopsy
Evidence of hepatocellular carcinoma (HCC)
Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
Significant renal, cardiovascular, pulmonary, or neurological disease
Received solid organ or bone marrow transplantation
Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
Has proximal tubulopathy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00117676

Show 113 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Chair:

Elsa Mondou, M.D.

Gilead Sciences

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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.

Responsible Party:	Gilead Sciences ( Elsa Mondou, MD )
Study ID Numbers:	GS-US-174-0102
Study First Received:	June 30, 2005
Last Updated:	August 27, 2008
ClinicalTrials.gov Identifier:	NCT00117676 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:

tenofovir
adefovir
hepatitis B virus
HBeAg Negative

Additional relevant MeSH terms:

Anti-Infective Agents
Liver Diseases
Anti-HIV Agents
Molecular Mechanisms of Pharmacological Action
Hepatitis, Chronic
Hepatitis, Viral, Human
Enzyme Inhibitors
Antiviral Agents
Hepadnaviridae Infections
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Hepatitis

Virus Diseases
Digestive System Diseases
Anti-Retroviral Agents
Therapeutic Uses
Hepatitis B, Chronic
Hepatitis B
Tenofovir
DNA Virus Infections
Adefovir dipivoxil
Adefovir
Nucleic Acid Synthesis Inhibitors
Tenofovir disoproxil

ClinicalTrials.gov processed this record on November 27, 2009