search
Back to results

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

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
tenofovir DF
emtricitabine /tenofovir DF
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: 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 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

TDF

FTC/TDF

Outcomes

Primary Outcome Measures

Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48

Secondary Outcome Measures

Change From Baseline in log10 Plasma HBV DNA Levels at Week 48
Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 48
Percentage of Participants With Normal ALT at Week 48
ULN for males = 43 U/L; 34 U/L for females
Percentage of Participants With Normalized ALT at Week 48
Subjects with elevated ALT at baseline that return to normal by Week 48.
Hepatitis B Early Antigen (HBeAg) Loss at Week 48
Defined as having negative serum HBeAg for subjects with positive HBeAg at baseline.
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.
HBsAg Loss at Week 48
Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.
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.
Change From Baseline in log10 Plasma HBV DNA Levels at Week 168
Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 168
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168
Percentage of Participants With Normal ALT at Week 168
ULN for males = 43 U/L; ULN for females = 34 U/L
Percentage of Participants With Normalized ALT at Week 168
Subjects with elevated ALT at baseline that return to normal by Week 48.
Hepatitis B Early Antigen (HBeAg) Loss at Week 168
Defined as having negative serum HBeAg for subjecst with positive HBeAg at baseline.
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.
HBsAg Loss at Week 168
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
P-values were from a Cochran-Mantel-Haenszel test, controlling for baseline HBeAg status and prior lamivudine use.

Full Information

First Posted
March 24, 2006
Last Updated
October 4, 2011
Sponsor
Gilead Sciences
search

1. Study Identification

Unique Protocol Identification Number
NCT00307489
Brief Title
Treatment of Persistent Viremia (Virus in Blood) in Chronic Hepatitis B Subjects Already Receiving Adefovir Dipivoxil
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
106 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
TDF
Arm Title
2
Arm Type
Experimental
Arm Description
FTC/TDF
Intervention Type
Drug
Intervention Name(s)
tenofovir DF
Intervention Description
300 mg tablet, once daily (QD)
Intervention Type
Drug
Intervention Name(s)
emtricitabine /tenofovir DF
Intervention Description
emtricitabine 200 mg/tenofovir DF 300 mg once daily (combination tablet)
Primary Outcome Measure Information:
Title
Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48
Time Frame
48 weeks
Title
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48
Time Frame
48 Weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in log10 Plasma HBV DNA Levels at Week 48
Time Frame
48 Weeks
Title
Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 48
Time Frame
48 Weeks
Title
Percentage of Participants With Normal ALT at Week 48
Description
ULN for males = 43 U/L; 34 U/L for females
Time Frame
48 Weeks
Title
Percentage of Participants With Normalized ALT at Week 48
Description
Subjects with elevated ALT at baseline that return to normal by Week 48.
Time Frame
48 Weeks
Title
Hepatitis B Early Antigen (HBeAg) Loss at Week 48
Description
Defined as having negative serum HBeAg for subjects with positive HBeAg at baseline.
Time Frame
48 Weeks
Title
HBeAg Seroconversion at Week 48
Description
Defined as having negative serum HBeAg and positive serum antibody to HBeAg [anti-HBe] for subjects with positive serum HBeAg at baseline.
Time Frame
48 Weeks
Title
HBsAg Loss at Week 48
Description
Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.
Time Frame
48 Weeks
Title
Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 48
Description
Defined as having negative serum HBsAg and positive serum antibody to HBsAg [anti-HBs] for subject with positive serum HBsAg at baseline.
Time Frame
48 Weeks
Title
Change From Baseline in log10 Plasma HBV DNA Levels at Week 168
Time Frame
168 weeks
Title
Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 168
Time Frame
168 weeks
Title
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168
Time Frame
168 weeks
Title
Percentage of Participants With Normal ALT at Week 168
Description
ULN for males = 43 U/L; ULN for females = 34 U/L
Time Frame
168 weeks
Title
Percentage of Participants With Normalized ALT at Week 168
Description
Subjects with elevated ALT at baseline that return to normal by Week 48.
Time Frame
168 weeks
Title
Hepatitis B Early Antigen (HBeAg) Loss at Week 168
Description
Defined as having negative serum HBeAg for subjecst with positive HBeAg at baseline.
Time Frame
168 weeks
Title
Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 168
Description
Defined as having negative serum BHsAg and positive serum antibody to HBsAg (anti-HBs) for subject with positive serum BHsAg at baseline.
Time Frame
168 weeks
Title
HBsAg Loss at Week 168
Description
Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.
Time Frame
168 weeks
Title
Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 168
Description
P-values were from a Cochran-Mantel-Haenszel test, controlling for baseline HBeAg status and prior lamivudine use.
Time Frame
168 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility 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: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen J Rossi, PharmD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
San Jose
State/Province
California
ZIP/Postal Code
95128
Country
United States
City
Flushing
State/Province
New York
ZIP/Postal Code
11355
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10013
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
City
Angers
ZIP/Postal Code
49933
Country
France
City
Clichy
ZIP/Postal Code
92110
Country
France
City
Lille
ZIP/Postal Code
59037
Country
France
City
Lyon
ZIP/Postal Code
69288
Country
France
City
Marseille
ZIP/Postal Code
13285
Country
France
City
Rouen
ZIP/Postal Code
76031
Country
France
City
Strasbourg
ZIP/Postal Code
67091
Country
France
City
Berlin
ZIP/Postal Code
10969
Country
Germany
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Bonn
ZIP/Postal Code
53105
Country
Germany
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
City
Essen
ZIP/Postal Code
45122
Country
Germany
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
City
Hamburg
ZIP/Postal Code
20999
Country
Germany
City
Hannover
ZIP/Postal Code
30623
Country
Germany
City
Herne
ZIP/Postal Code
44623
Country
Germany
City
Munchen
ZIP/Postal Code
81377
Country
Germany
City
Sevilla
ZIP/Postal Code
41014
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
16871563
Citation
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.
Results Reference
result
PubMed Identifier
19052126
Citation
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.
Results Reference
result
PubMed Identifier
18191272
Citation
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.
Results Reference
result
PubMed Identifier
18199519
Citation
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.
Results Reference
result
PubMed Identifier
19998272
Citation
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.
Results Reference
result
PubMed Identifier
20600025
Citation
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs