Back to resultsA Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tenofovir DF
FTC
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring tenofovir, monotherapy, emtricitabine, combination, hepatitis B
Eligibility Criteria
Inclusion Criteria:
- Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive > 3 months and positive for immunoglobulin G antibody against hepatitis B core antigen
- 18 through 69 years of age, inclusive
- Hepatitis B e antigen (HBeAg) positive
- HBV DNA ≥ 10^8 copies/mL
- ALT ≤ the upper limit of the normal range (ULN)
- Willing and able to provide written informed consent
- Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)
- Calculated creatinine clearance ≥ 70 mL/min
- Hemoglobin ≥ 10 g/dL
- Neutrophils ≥ 1,500/mm^3
- No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
Exclusion Criteria:
- Pregnant women, women who were breast feeding, or who believed they may have wished to become pregnant during the course of the study
- Males and females of reproductive potential unwilling to use an effective method of contraception during the study
- Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, prothrombin time > 1.2 x ULN, platelets < 150,000/mm^3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, or variceal hemorrhage)
- Received interferon (pegylated or not) therapy within 6 months of the screening visit
- Alpha-fetoprotein > 50 ng/mL
- Evidence of hepatocellular carcinoma
- Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus
- Significant renal, cardiovascular, pulmonary, or neurological disease
- Received solid organ or bone marrow transplantation
- Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
- Had proximal tubulopathy
- Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Tenofovir DF
FTC+Tenofovir DF
Arm Description
Participants were randomized to receive tenofovir DF plus placebo to match FTC once daily.
Participants were randomized to receive FTC plus tenofovir DF once daily.
Outcomes
Primary Outcome Measures
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192
The percentage of participants with HBV DNA < 400 copies/mL at Week 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Secondary Outcome Measures
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144
The percentage of participants with HBV DNA < 400 copies/mL at Weeks 48, 96, and 144 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192
The percentage of participants with HBV DNA < 169 copies/mL at Weeks 48, 96, 144, and 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Change From Baseline in HBV DNA at Week 48
The change from baseline in HBV DNA at Week 48 was analyzed.
Change From Baseline in HBV DNA at Week 96
The change from baseline in HBV DNA at Week 96 was analyzed.
Change From Baseline in HBV DNA at Week 144
The change from baseline in HBV DNA at Week 144 was analyzed.
Change From Baseline in HBV DNA at Week 192
The change from baseline in HBV DNA at Week 192 was analyzed.
Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192
Range of normal ALT was 6 to 34 U/L for females, 6 to 43 U/L for males. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192
The number of participants with HBeAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative.
No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.
Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192
The number of participants with seroconversion to anti-HBe at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive.
No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.
Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192
The number of participants with HBsAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.
Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192
The number of participants with seroconversion to anti-HBs at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.
Occurrence of HBV Resistance Mutations
The development of HBV resistance mutations (occurrence of conserved site changes and/or polymorphic site changes) was analyzed for the overall study period (through Week 192).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00507507
Brief Title
A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)
Official Title
A Randomized, Double-Blind Study Evaluating Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus the Combination of Emtricitabine and Tenofovir DF for the Treatment of Chronic Hepatitis B
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The main objective of the study was to evaluate the antiviral activity of tenofovir disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the immune tolerant phase of HBV infection.
The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy was evaluated for suppression of the virus (decrease in HBV DNA), serological response (generation of antibodies to the virus), biochemical response (changes in liver enzymes), and the development of drug-resistant mutations. The safety and tolerability of both tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for adverse events and changes in laboratory parameters.
Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus tenofovir DF. All subjects were to continue on blinded study medication until the last subject reached Week 192. Participants who permanently discontinued study drug (on or before Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject reached Week 192.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
tenofovir, monotherapy, emtricitabine, combination, hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
126 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tenofovir DF
Arm Type
Experimental
Arm Description
Participants were randomized to receive tenofovir DF plus placebo to match FTC once daily.
Arm Title
FTC+Tenofovir DF
Arm Type
Experimental
Arm Description
Participants were randomized to receive FTC plus tenofovir DF once daily.
Intervention Type
Drug
Intervention Name(s)
Tenofovir DF
Other Intervention Name(s)
Viread®
Intervention Description
Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily
Intervention Type
Drug
Intervention Name(s)
FTC
Other Intervention Name(s)
Emtriva®
Intervention Description
Emtricitabine (FTC) 200 mg capsule taken orally once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to match FTC taken once daily
Primary Outcome Measure Information:
Title
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192
Description
The percentage of participants with HBV DNA < 400 copies/mL at Week 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Time Frame
Week 192
Secondary Outcome Measure Information:
Title
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144
Description
The percentage of participants with HBV DNA < 400 copies/mL at Weeks 48, 96, and 144 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Time Frame
Weeks 48, 96, and 144
Title
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192
Description
The percentage of participants with HBV DNA < 169 copies/mL at Weeks 48, 96, 144, and 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Time Frame
Weeks 48, 96, 144, and 192
Title
Change From Baseline in HBV DNA at Week 48
Description
The change from baseline in HBV DNA at Week 48 was analyzed.
Time Frame
Baseline to Week 48
Title
Change From Baseline in HBV DNA at Week 96
Description
The change from baseline in HBV DNA at Week 96 was analyzed.
Time Frame
Baseline to Week 96
Title
Change From Baseline in HBV DNA at Week 144
Description
The change from baseline in HBV DNA at Week 144 was analyzed.
Time Frame
Baseline to Week 144
Title
Change From Baseline in HBV DNA at Week 192
Description
The change from baseline in HBV DNA at Week 192 was analyzed.
Time Frame
Baseline to Week 192
Title
Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192
Description
Range of normal ALT was 6 to 34 U/L for females, 6 to 43 U/L for males. Participants with missing data were considered to have failed to achieve the criteria for evaluation.
Time Frame
Weeks 48, 96, 144, and 192
Title
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192
Description
The number of participants with HBeAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative.
No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.
Time Frame
Weeks 48, 96, 144, and 192
Title
Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192
Description
The number of participants with seroconversion to anti-HBe at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive.
No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.
Time Frame
Weeks 48, 96, 144, and 192
Title
Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192
Description
The number of participants with HBsAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.
Time Frame
Weeks 48, 96, 144, and 192
Title
Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192
Description
The number of participants with seroconversion to anti-HBs at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.
Time Frame
Weeks 48, 96, 144, and 192
Title
Occurrence of HBV Resistance Mutations
Description
The development of HBV resistance mutations (occurrence of conserved site changes and/or polymorphic site changes) was analyzed for the overall study period (through Week 192).
Time Frame
Baseline to Week 192
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:
Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive > 3 months and positive for immunoglobulin G antibody against hepatitis B core antigen
18 through 69 years of age, inclusive
Hepatitis B e antigen (HBeAg) positive
HBV DNA ≥ 10^8 copies/mL
ALT ≤ the upper limit of the normal range (ULN)
Willing and able to provide written informed consent
Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)
Calculated creatinine clearance ≥ 70 mL/min
Hemoglobin ≥ 10 g/dL
Neutrophils ≥ 1,500/mm^3
No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
Exclusion Criteria:
Pregnant women, women who were breast feeding, or who believed they may have wished to become pregnant during the course of the study
Males and females of reproductive potential unwilling to use an effective method of contraception during the study
Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, prothrombin time > 1.2 x ULN, platelets < 150,000/mm^3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, or variceal hemorrhage)
Received interferon (pegylated or not) therapy within 6 months of the screening visit
Alpha-fetoprotein > 50 ng/mL
Evidence of hepatocellular carcinoma
Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus
Significant renal, cardiovascular, pulmonary, or neurological disease
Received solid organ or bone marrow transplantation
Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
Had proximal tubulopathy
Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
Facility Information:
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92115
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
11355
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029-6574
Country
United States
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98111
Country
United States
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
City
Heidelburg
State/Province
Victoria
ZIP/Postal Code
3081
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N4N1
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z1H2
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
City
Lille
ZIP/Postal Code
59037
Country
France
City
Lyon
ZIP/Postal Code
69288
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
Duesseldorf
ZIP/Postal Code
40237
Country
Germany
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
City
Hamburg
ZIP/Postal Code
20251
Country
Germany
City
Hannover
ZIP/Postal Code
30623
Country
Germany
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
City
Herne
ZIP/Postal Code
44623
Country
Germany
City
Mainz
ZIP/Postal Code
55131
Country
Germany
City
Pokfulam
Country
Hong Kong
City
Shatin
Country
Hong Kong
City
Tai Po
Country
Hong Kong
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1150
Country
New Zealand
City
Hamilton
Country
New Zealand
City
Bydgoszcz
ZIP/Postal Code
85-030
Country
Poland
City
Chorzow
ZIP/Postal Code
41-500
Country
Poland
City
Warszawa
ZIP/Postal Code
01-201
Country
Poland
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
City
Singapore
ZIP/Postal Code
529889
Country
Singapore
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
City
Kaoshiung
ZIP/Postal Code
833
Country
Taiwan
City
Tainan
ZIP/Postal Code
107
Country
Taiwan
City
Taipei
Country
Taiwan
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)
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