Chronic Hepatitis B
Conditions
Keywords
Hepatitis; Hepatitis B virus; Tenofovir
Brief summary
This study was designed to evaluate and compare the safety and tolerability of tenofovir disoproxil fumarate (TDF), emtricitabine (FTC)/TDF, and entecavir (ETV) in the treatment of hepatitis B patients with decompensated liver disease. Safety was assessed by evaluating adverse events (AEs) and laboratory abnormalities. Efficacy was assessed by evaluating reductions in Child-Pugh-Turcotte (CPT) and Model for End Stage Liver Disease (MELD) scores, reductions in hepatitis B virus (HBV) deoxyribonucleic acid (DNA), changes in liver enzymes, development of drug-resistant mutations, and generation of antibody to virus. A maximum randomized treatment duration of 168 weeks was planned. Since subjects with decompensated liver disease were enrolled into this study, it was necessary to provide early intervention strategies if profound viral suppression was not expeditiously achieved. For this reason, subjects with a decrease in plasma HBV DNA from baseline of \< 2 log\_10 copies/mL and plasma HBV DNA \> 10,000 copies/mL (or plasma HBV DNA \> 1,000 copies/mL for subjects who entered the study with HBV DNA \< 10,000 copies/mL) at Week 8 had the option to start open-label FTC/TDF and continue in the study. Subjects with a virologic breakthrough or who had plasma HBV DNA levels remaining \> 400 copies/mL (confirmed) at or after 24 weeks of treatment could have been unblinded at the investigator's discretion for selection of alternative anti-HBV therapy that may have included open-label FTC/TDF. If study drug was permanently discontinued, immediate initiation of another anti-HBV regimen was strongly recommended.
Interventions
DRUGTenofovir disoproxil fumarate (tenofovir DF; TDF)
300-mg tablet QD
FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet QD
DRUGEntecavir (ETV)
0.5-mg or 1-mg tablet QD
DRUGTDF placebo
Placebo to match TDF QD
DRUGFTC/TDF placebo
Placebo to match FTC/TDF QD
DRUGETV placebo
Placebo to match ETV QD
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
A participant was required to meet all of the following inclusion criteria to be eligible for participation in the study: * Chronic Hepatitis B infection * 18 through 69 years of age, inclusive * HBV DNA ≥ 1000 copies/mL * Decompensated liver disease with all of the following: * CPT score of 7-12 (inclusive) OR history of CPT score ≥ 7 and any CPT at screen ≤ 12 * Serum alanine aminotransferase (ALT) \< 10 x the upper limit of the normal range (ULN) * Hemoglobin ≥ 7.5 g/dL * Total white blood cell (WBC) count ≥ 1,500/mm\^3 * Platelet count ≥ 30,000/mm\^3 * Alpha-fetoprotein ≤ 20 ng/mL and ultrasound or other imaging with no evidence of hepatocellular carcinoma (HCC), or alpha-fetoprotein of 21-50 ng/mL and computed tomography (CT)/magnetic resonance imaging (MRI) scan with no evidence of HCC, within 6 months of screening * Calculated creatinine clearance ≥ 50 mL/min * Negative human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis D virus (HDV) serologies * Less than 24 months of total prior adefovir dipivoxil exposure * Willing and able to provide written informed consent
Exclusion criteria
A participant who met any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL | Baseline to Week 168 | Results are expressed as proportions of participants who experience a confirmed increase in serum creatinine of ≥ 0.5 mg/dL from baseline or a confirmed serum phosphorus level \< 2.0 mg/dL using the KM method of estimation. |
| Percent Probability of Tolerability Failure | Baseline to Week 168 | Tolerability failure was defined as permanent discontinuation of study drug due to a treatment-emergent adverse event (AE), including any subject who temporarily discontinued study drug due to an AE and did not restart. Results are expressed as proportions of participants who experience tolerability failure using the Kaplan-Meier (KM) method of estimation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline | Baseline to 144 weeks | Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 144 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value. |
| Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline | Baseline to 168 weeks | Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 168 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value. |
| Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48 | Week 48 | The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 48 was summarized. |
| Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96 | Week 96 | The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 96 was summarized. |
| Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144 | Week 144 | The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 144 was summarized. |
| Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168 | Week 168 | The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 168 was summarized. |
| Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48 | Baseline to Week 48 | CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline | Baseline to 96 weeks | Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 96 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value. |
| Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | Baseline to Week 144 | Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. |
| Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | Baseline to Week 168 | Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. |
| In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results | Baseline to Week 168 | — |
| Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48 | Baseline to Week 48 | Normalized ALT is defined as having a baseline ALT value \> the upper limit of the normal range (ULN), and a decrease in ALT value to ≤ ULN at the given time point. |
| Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96 | Baseline to Week 96 | Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point. |
| Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144 | Baseline to Week 144 | Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point. |
| Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168 | Baseline to Week 168 | Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point. |
| Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48 | Baseline to Week 48 | CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96 | Baseline to Week 96 | CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144 | Baseline to Week 144 | CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168 | Baseline to Week 168 | CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline | Baseline to 48 weeks | Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 48 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value. |
| Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96 | Baseline to Week 96 | CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144 | Baseline to Week 144 | CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168 | Baseline to Week 168 | CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48 | Baseline to Week 48 | MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity. |
| Median Change in MELD Score From Baseline at Week 96 | Baseline to Week 96 | MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity. |
| Median Change in MELD Score From Baseline at Week 144 | Baseline to Week 144 | MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity. |
| Median Change in MELD Score From Baseline at Week 168 | Baseline to Week 168 | MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity. |
| Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | Baseline to Week 48 | Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. |
| Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | Baseline to Week 96 | Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. |
| Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | Baseline to Week 144 | Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. |
| Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | Baseline to Week 168 | Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | Baseline to Week 48 | Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. |
| Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | Baseline to Week 96 | Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Baseline ADV-R + LAM-R Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | Baseline to Week 168 | ADV resistance mutation + LAM resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation, and the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation. |
| Percentage of Participants With Only Baseline Adefovir Dipivoxil Resistance (ADV-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | Baseline to Week 168 | ADV resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation. |
| Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | Baseline to Week 168 | LAM resistance mutations are defined as the presence of the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation. |
Countries
Canada, France, Germany, Greece, Italy, Poland, Singapore, Spain, Taiwan, Turkey (Türkiye), United States
Participant flow
Recruitment details
Of the 112 participants randomized, 43 were in Taiwan or Singapore, 43 were in Europe (Turkey, Spain, Germany, Greece, Poland, Italy, or France), and 26 were in the US or Canada. The first participant was screened on 04 April 2006, and the last participant was randomized on 03 January 2008. Last participant observation date was 12 April 2011.
Pre-assignment details
196 participants screened; 112 randomized and treated (full analysis set; randomized analysis set). Subjects without adequate decrease in HBV DNA at Week 8 could start open-label FTC/TDF. Subjects with virologic breakthrough or HBV DNA levels \> 400 copies/mL at ≥ 24 weeks could have received other therapy that may have included open-label FTC/TDF.
Participants by arm
| Arm | Count |
|---|---|
| Tenofovir DF Participants in this group were randomized to receive TDF 300 mg + FTC/TDF placebo + ETV placebo at baseline | 45 |
| FTC/TDF Participants in this group were randomized to receive FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo at baseline | 45 |
| Entecavir Participants in this group were randomized to receive ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo at baseline | 22 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 2 |
| Overall Study | Lack of Efficacy | 2 | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 4 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 3 |
Baseline characteristics
| Characteristic | Tenofovir DF | FTC/TDF | Entecavir | Total |
|---|---|---|---|---|
| Age Continuous | 53 years STANDARD_DEVIATION 8.8 | 49 years STANDARD_DEVIATION 10.1 | 52 years STANDARD_DEVIATION 12 | 51 years STANDARD_DEVIATION 10 |
| BMI | 27.6 kg/m^2 STANDARD_DEVIATION 5.67 | 26.2 kg/m^2 STANDARD_DEVIATION 5.07 | 27.6 kg/m^2 STANDARD_DEVIATION 5.27 | 27.0 kg/m^2 STANDARD_DEVIATION 5.35 |
| Ethnicity Hispanic or Latino | 2 participants | 1 participants | 0 participants | 3 participants |
| Ethnicity Not Hispanic or Latino | 39 participants | 39 participants | 21 participants | 99 participants |
| Ethnicity Not Permitted | 4 participants | 5 participants | 1 participants | 10 participants |
| Height | 168.3 cm STANDARD_DEVIATION 7.98 | 168.4 cm STANDARD_DEVIATION 8.47 | 167.1 cm STANDARD_DEVIATION 8.39 | 168.1 cm STANDARD_DEVIATION 8.2 |
| Race Asian | 23 participants | 24 participants | 13 participants | 60 participants |
| Race Black | 1 participants | 1 participants | 0 participants | 2 participants |
| Race Other | 2 participants | 0 participants | 1 participants | 3 participants |
| Race White | 19 participants | 20 participants | 8 participants | 47 participants |
| Region of Enrollment Canada | 4 participants | 7 participants | 1 participants | 12 participants |
| Region of Enrollment France | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Germany | 4 participants | 1 participants | 1 participants | 6 participants |
| Region of Enrollment Greece | 4 participants | 1 participants | 1 participants | 6 participants |
| Region of Enrollment Italy | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Poland | 2 participants | 2 participants | 2 participants | 6 participants |
| Region of Enrollment Singapore | 1 participants | 3 participants | 1 participants | 5 participants |
| Region of Enrollment Spain | 2 participants | 6 participants | 2 participants | 10 participants |
| Region of Enrollment Taiwan | 13 participants | 16 participants | 9 participants | 38 participants |
| Region of Enrollment Turkey | 4 participants | 6 participants | 2 participants | 12 participants |
| Region of Enrollment United States | 10 participants | 2 participants | 2 participants | 14 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Male | 37 Participants | 40 Participants | 17 Participants | 94 Participants |
| Weight | 78.1 kg STANDARD_DEVIATION 17.02 | 74.4 kg STANDARD_DEVIATION 15.41 | 77.3 kg STANDARD_DEVIATION 16.64 | 76.5 kg STANDARD_DEVIATION 16.26 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 41 / 45 | 44 / 45 | 20 / 22 | 9 / 12 | 89 / 93 |
| serious Total, serious adverse events | 21 / 45 | 25 / 45 | 11 / 22 | 4 / 12 | 50 / 93 |
Outcome results
Primary
Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL
Results are expressed as proportions of participants who experience a confirmed increase in serum creatinine of ≥ 0.5 mg/dL from baseline or a confirmed serum phosphorus level \< 2.0 mg/dL using the KM method of estimation.
Time frame: Baseline to Week 168
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL | 15 percent probability (KM estimate) |
| FTC/TDF | Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL | 14 percent probability (KM estimate) |
| TDF or FTC/TDF | Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL | 14 percent probability (KM estimate) |
| Entecavir | Percent Probability of a Confirmed Increase in Serum Creatinine of ≥ 0.5 mg/dL From Baseline or a Confirmed Serum Phosphorus Level < 2.0 mg/dL | 10 percent probability (KM estimate) |
Primary
Percent Probability of Tolerability Failure
Tolerability failure was defined as permanent discontinuation of study drug due to a treatment-emergent adverse event (AE), including any subject who temporarily discontinued study drug due to an AE and did not restart. Results are expressed as proportions of participants who experience tolerability failure using the Kaplan-Meier (KM) method of estimation.
Time frame: Baseline to Week 168
Population: Full analysis set (all randomized subjects who received at least one dose of study drug)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percent Probability of Tolerability Failure | 18 percent probability (KM estimate) |
| FTC/TDF | Percent Probability of Tolerability Failure | 4 percent probability (KM estimate) |
| TDF or FTC/TDF | Percent Probability of Tolerability Failure | 11 percent probability (KM estimate) |
| Entecavir | Percent Probability of Tolerability Failure | 14 percent probability (KM estimate) |
Secondary
In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results
Time frame: Baseline to Week 168
Population: Liver transplantation analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results | NA Days |
| FTC/TDF | In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results | NA Days |
| TDF or FTC/TDF | In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results | NA Days |
| Entecavir | In the Subset of Participants Undergoing Liver Transplantation, Time to Recurrence of Hepatitis B, Defined as 2 Consecutive Plasma HBV DNA Concentrations ≥ 400 Copies/mL or 2 Consecutive HBsAg(+) Results | NA Days |
Secondary
Median Change in MELD Score From Baseline at Week 144
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline to Week 144
Population: Subjects in the full analysis set with an available score at the visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Median Change in MELD Score From Baseline at Week 144 | -2.0 units on a scale |
| FTC/TDF | Median Change in MELD Score From Baseline at Week 144 | -1.5 units on a scale |
| TDF or FTC/TDF | Median Change in MELD Score From Baseline at Week 144 | -2.0 units on a scale |
| Entecavir | Median Change in MELD Score From Baseline at Week 144 | -2.0 units on a scale |
Secondary
Median Change in MELD Score From Baseline at Week 168
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline to Week 168
Population: Subjects in the full analysis set with an available score at the visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Median Change in MELD Score From Baseline at Week 168 | -2.0 units on a scale |
| FTC/TDF | Median Change in MELD Score From Baseline at Week 168 | -2.0 units on a scale |
| TDF or FTC/TDF | Median Change in MELD Score From Baseline at Week 168 | -2.0 units on a scale |
| Entecavir | Median Change in MELD Score From Baseline at Week 168 | -2.0 units on a scale |
Secondary
Median Change in MELD Score From Baseline at Week 96
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline to Week 96
Population: Subjects in the full analysis set with an available score at the visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Median Change in MELD Score From Baseline at Week 96 | -2.0 units on a scale |
| FTC/TDF | Median Change in MELD Score From Baseline at Week 96 | -3.0 units on a scale |
| TDF or FTC/TDF | Median Change in MELD Score From Baseline at Week 96 | -3.0 units on a scale |
| Entecavir | Median Change in MELD Score From Baseline at Week 96 | -2.0 units on a scale |
Secondary
Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48
MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline to Week 48
Population: Subjects in the full analysis set with an available score at the visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48 | -2.0 units on a scale |
| FTC/TDF | Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48 | -2.0 units on a scale |
| TDF or FTC/TDF | Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48 | -2.0 units on a scale |
| Entecavir | Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48 | -2.0 units on a scale |
Secondary
Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline
Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 144 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Time frame: Baseline to 144 weeks
Population: Full analysis set; data collected for participants who underwent liver transplant prior to Week 144 were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline | -3.07 log _10 copies/mL |
| FTC/TDF | Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline | -3.82 log _10 copies/mL |
| TDF or FTC/TDF | Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline | -3.76 log _10 copies/mL |
| Entecavir | Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline | -3.49 log _10 copies/mL |
Secondary
Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline
Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 168 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Time frame: Baseline to 168 weeks
Population: Full analysis set; data collected for participants who underwent liver transplant prior to Week 168 were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline | -3.16 log_10 copies/mL |
| FTC/TDF | Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline | -4.06 log_10 copies/mL |
| TDF or FTC/TDF | Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline | -3.77 log_10 copies/mL |
| Entecavir | Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline | -3.66 log_10 copies/mL |
Secondary
Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline
Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 96 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Time frame: Baseline to 96 weeks
Population: Full analysis set; data collected for participants who underwent liver transplant prior to Week 96 were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline | -3.06 log_10 copies/mL |
| FTC/TDF | Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline | -4.06 log_10 copies/mL |
| TDF or FTC/TDF | Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline | -3.32 log_10 copies/mL |
| Entecavir | Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline | -3.40 log_10 copies/mL |
Secondary
Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline
Change from baseline was evaluated by subtracting baseline HBV DNA log\_10 copies/mL from Week 48 HBV DNA log\_10 copies/mL. DAVG is defined as the area of the trapezoid under the response-time curve divided by time to the last available evaluation of the patient minus the baseline value.
Time frame: Baseline to 48 weeks
Population: Participants with HBV DNA measurements at Week 48 were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline | -2.93 log_10 copies/mL |
| FTC/TDF | Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline | -3.45 log_10 copies/mL |
| TDF or FTC/TDF | Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline | -3.61 log_10 copies/mL |
| Entecavir | Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline | -3.19 log_10 copies/mL |
Secondary
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 144
Population: CPT evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144 | 25.9 percentage of participants |
| FTC/TDF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144 | 51.9 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144 | 45.5 percentage of participants |
| Entecavir | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144 | 40.0 percentage of participants |
Secondary
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 168
Population: CPT evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168 | 24.0 percentage of participants |
| FTC/TDF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168 | 45.8 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168 | 45.5 percentage of participants |
| Entecavir | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168 | 36.7 percentage of participants |
Secondary
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 48
Population: CPT evaluable analysis set (subjects with CPT scores ≥ 7 at baseline; because the minimum CPT score was 5, only these subjects were evaluable for analyses of ≥ 2-point decrease in CPT score); noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48 | 25.9 percentage of participants |
| FTC/TDF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48 | 48.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48 | 41.7 percentage of participants |
| Entecavir | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48 | 37.5 percentage of participants |
Secondary
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 96
Population: CPT evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96 | 23.1 percentage of participants |
| FTC/TDF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96 | 52.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96 | 50.0 percentage of participants |
| Entecavir | Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96 | 39.3 percentage of participants |
Secondary
Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 48
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48 | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48 | 2.6 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48 | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48 | 1.0 percentage of participants |
Secondary
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 144
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144 | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144 | 2.5 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144 | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144 | 1.0 percentage of participants |
Secondary
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 168
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168 | 2.4 percentage of participants |
| FTC/TDF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168 | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168 | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168 | 1.0 percentage of participants |
Secondary
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96
CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline to Week 96
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96 | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96 | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96 | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96 | 0.0 percentage of participants |
Secondary
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline)
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline to Week 144
Population: Serologically evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 14.3 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 14.3 percentage of participants |
| FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 13.3 percentage of participants |
| FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 33.3 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 16.7 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 22.9 percentage of participants |
| Entecavir | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 11.4 percentage of participants |
Secondary
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline)
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline to Week 168
Population: Serologically evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 23.1 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 23.1 percentage of participants |
| FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 21.4 percentage of participants |
| FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 35.7 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 16.7 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 27.3 percentage of participants |
| Entecavir | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 18.2 percentage of participants |
Secondary
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline)
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline to Week 96
Population: Serologically evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 14.3 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 14.3 percentage of participants |
| FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 13.3 percentage of participants |
| FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 33.3 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 20.0 percentage of participants |
| Entecavir | Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 11.4 percentage of participants |
Secondary
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline to Week 144
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | HBsAg Loss | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | HBsAg Seroconversion | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | HBsAg Seroconversion | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | HBsAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | HBsAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | HBsAg Seroconversion | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | HBsAg Loss | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144 | HBsAg Seroconversion | 0.0 percentage of participants |
Secondary
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline to Week 168
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | HBsAg Loss | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | HBsAg Seroconversion | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | HBsAg Seroconversion | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | HBsAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | HBsAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | HBsAg Seroconversion | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | HBsAg Loss | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168 | HBsAg Seroconversion | 0.0 percentage of participants |
Secondary
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline to Week 96
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | HBsAg Loss | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | HBsAg Seroconversion | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | HBsAg Seroconversion | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | HBsAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | HBsAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | HBsAg Seroconversion | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | HBsAg Loss | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96 | HBsAg Seroconversion | 0.0 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline)
Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive.
Time frame: Baseline to Week 48
Population: Serologically evaluable analysis set (subjects in full analysis set with positive hepatitis B early antigen \[HBeAg\] at baseline); noncompleters/switch = failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 21.4 percentage of participants |
| Tenofovir DF | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 21.4 percentage of participants |
| FTC/TDF | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 13.3 percentage of participants |
| FTC/TDF | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 26.7 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Loss | 19.4 percentage of participants |
| Entecavir | Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline) | HBeAg Seroconversion | 13.9 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive.
Time frame: Baseline to Week 48
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | HBsAg Loss | 0.0 percentage of participants |
| Tenofovir DF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | HBsAg Seroconversion | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | HBsAg Seroconversion | 0.0 percentage of participants |
| FTC/TDF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | HBsAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | HBsAg Loss | 0.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | HBsAg Seroconversion | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | HBsAg Loss | 0.0 percentage of participants |
| Entecavir | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48 | HBsAg Seroconversion | 0.0 percentage of participants |
Secondary
Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48
Normalized ALT is defined as having a baseline ALT value \> the upper limit of the normal range (ULN), and a decrease in ALT value to ≤ ULN at the given time point.
Time frame: Baseline to Week 48
Population: Biochemically evaluable analysis set (subjects in full analysis set with abnormal baseline alanine aminotransferase \[ALT\] values); noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48 | 46.2 percentage of participants |
| FTC/TDF | Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48 | 64.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48 | 41.2 percentage of participants |
| Entecavir | Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48 | 51.5 percentage of participants |
Secondary
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Time frame: Baseline to Week 144
Population: Biochemically evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144 | 34.6 percentage of participants |
| FTC/TDF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144 | 64.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144 | 37.5 percentage of participants |
| Entecavir | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144 | 46.3 percentage of participants |
Secondary
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Time frame: Baseline to Week 168
Population: Biochemically evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168 | 29.2 percentage of participants |
| FTC/TDF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168 | 60.0 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168 | 37.5 percentage of participants |
| Entecavir | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168 | 43.1 percentage of participants |
Secondary
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96
Normalized ALT is defined as having a baseline ALT value \> ULN, and a decrease in ALT value to ≤ ULN at the given time point.
Time frame: Baseline to Week 96
Population: Biochemically evaluable analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96 | 50.0 percentage of participants |
| FTC/TDF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96 | 58.3 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96 | 31.3 percentage of participants |
| Entecavir | Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96 | 48.5 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 144 was summarized.
Time frame: Week 144
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144 | 50.0 percentage of participants |
| FTC/TDF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144 | 77.5 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144 | 52.4 percentage of participants |
| Entecavir | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144 | 61.0 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 168 was summarized.
Time frame: Week 168
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168 | 50.0 percentage of participants |
| FTC/TDF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168 | 75.7 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168 | 52.4 percentage of participants |
| Entecavir | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168 | 60.0 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 48 was summarized.
Time frame: Week 48
Population: Full analysis set; noncompleters/switch = failure analysis (participants who did not complete treatment or changed from double-blind to open-label treatment up to the time point were considered as failing to meet efficacy response criteria \[defined as not achieving viral suppression of \< 400 copies/mL\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48 | 70.5 percentage of participants |
| FTC/TDF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48 | 87.8 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48 | 72.7 percentage of participants |
| Entecavir | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48 | 77.6 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96
The percentage of participants with plasma HBV DNA \< 400 copies/mL at Week 96 was summarized.
Time frame: Week 96
Population: Full analysis set; noncompleters/switch = failure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96 | 59.1 percentage of participants |
| FTC/TDF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96 | 79.5 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96 | 57.1 percentage of participants |
| Entecavir | Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96 | 66.3 percentage of participants |
Other Pre-specified
Percentage of Participants With Baseline ADV-R + LAM-R Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
ADV resistance mutation + LAM resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation, and the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation.
Time frame: Baseline to Week 168
Population: Participants in the full analysis set with both ADV and LAM resistance mutations at baseline were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Baseline ADV-R + LAM-R Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 50 percentage of participants |
Other Pre-specified
Percentage of Participants With Only Baseline Adefovir Dipivoxil Resistance (ADV-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
ADV resistance mutations are defined as the presence of the rtA181T/V HBV gene mutation and/or the rtN236T HBV gene mutation.
Time frame: Baseline to Week 168
Population: Participants in the full analysis set with ADV resistance mutation at baseline were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Only Baseline Adefovir Dipivoxil Resistance (ADV-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 100 percentage of participants |
| FTC/TDF | Percentage of Participants With Only Baseline Adefovir Dipivoxil Resistance (ADV-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 100 percentage of participants |
Other Pre-specified
Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
LAM resistance mutations are defined as the presence of the rtM204V/I HBV gene mutation with or without the rtL180M HBV gene mutation.
Time frame: Baseline to Week 168
Population: Patients in the full analysis set with LAM resistance mutation at baseline were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 100 percentage of participants |
| FTC/TDF | Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 100 percentage of participants |
| TDF or FTC/TDF | Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks | 100 percentage of participants |