Back to resultsStudy Comparing Tenofovir Disoproxil Fumarate (TDF), Emtricitabine (FTC)/TDF, and Entecavir (ETV) in the Treatment of Chronic HBV in Subjects With Decompensated Liver Disease.
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tenofovir disoproxil fumarate (tenofovir DF; TDF)
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
Entecavir (ETV)
TDF placebo
FTC/TDF placebo
ETV placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Hepatitis; Hepatitis B virus; Tenofovir
Eligibility Criteria
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 exclusion criteria could not be enrolled in the study: Pregnant women, women who were breastfeeding or who believed they may have wished to become pregnant during the course of the study Males and females of reproductive potential who were unwilling to use an effective method of contraception during the study Prior use of TDF or ETV History of variceal bleeding, hepatorenal syndrome, Grade 3 or 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 60 days of screening Grade 2 hepatic encephalopathy at screening History of solid organ or bone marrow transplant Current use of hepatotoxic drugs, nephrotoxic drugs, or drugs that interfere with renal tubular secretion Current therapy with immunomodulators (eg, corticosteroids, interleukin-2, etc.) or investigational drugs Diagnosis of proximal tubulopathy Use of investigational agent within 30 days prior to screening Known hypersensitivity to TDF, FTC, ETV, or formulation excipients of any of the study drug products
Sites / Locations
- Pfleger Liver Institute
- California Pacific Medical Center Research Institute
- University of Miami, Center for Liver Diseases
- Rush Presbyterian - St. Luke's Medical Center
- Henry Ford Hospital and Health System
- Mt. Sinai School of Medicine/ Mt. Sinai Medical Center
- Columbia Presbyterian Medical Center
- Metropolitan Research
- Virginia Mason Medical Center
- Heritage Medical Research Clinic
- Vancouver General Hospital
- The Gordon & Leslie Diamond Centre
- Toronto General Hospital
- Hopital Conception
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie
- Universitat Heidelberg
- Johannes Gutenberg-Universitat
- General Hospital of Athens "Ippokratio"
- Universita de Padova
- Policlinico Universitario
- Wojewodzki Szpital Specjalistyczny im Dluskeigo
- Wojewodzki Szpital Obserwacy
- Wojewodzki Szpital Zakazny
- National University Hospital Dept. of Gastroenterology & Hepatology
- Singapore General Hospital
- Tan Tock Seng Hospital
- Changi General Hospital
- Hospital General Universitari Vall d'Hebron
- Hospital Clinic i Provincial de Barcelona (HCPB)
- Hospital Universitario de Bellvitge
- Hospital General Universitario Gregorio Maranon
- Hospital Universitario y Politecnico la Fe
- Chang Gung Memorial Hospital - Kaohsiung
- National Cheng Kung University Hospital
- Chang-Gung Memorial Hospital
- Cathay General Hospital
- Marmara Universitesi School of Medicine
- Ege Universitesi Tip Fakultesi Hastanesi
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Tenofovir DF
FTC/TDF
Entecavir
Arm Description
TDF 300 mg + FTC/TDF placebo + ETV placebo once daily (QD)
FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo QD
ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo QD
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00298363
Brief Title
Study Comparing Tenofovir Disoproxil Fumarate (TDF), Emtricitabine (FTC)/TDF, and Entecavir (ETV) in the Treatment of Chronic HBV in Subjects With Decompensated Liver Disease.
Official Title
A Phase 2, Double-Blind, Multi-center, Randomized Study Comparing Tenofovir Disoproxil Fumarate, Emtricitabine Plus Tenofovir Disoproxil Fumarate, and Entecavir in the Treatment of Chronic Hepatitis B Subjects With Decompensated Liver Disease and in the Prevention of Hepatitis B Recurrence Post-Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Hepatitis; Hepatitis B virus; Tenofovir
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
112 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tenofovir DF
Arm Type
Experimental
Arm Description
TDF 300 mg + FTC/TDF placebo + ETV placebo once daily (QD)
Arm Title
FTC/TDF
Arm Type
Experimental
Arm Description
FTC 200 mg/TDF 300 mg + TDF placebo + ETV placebo QD
Arm Title
Entecavir
Arm Type
Experimental
Arm Description
ETV 0.5 mg or 1 mg + TDF placebo + FTC/TDF placebo QD
Intervention Type
Drug
Intervention Name(s)
Tenofovir disoproxil fumarate (tenofovir DF; TDF)
Other Intervention Name(s)
Viread
Intervention Description
300-mg tablet QD
Intervention Type
Drug
Intervention Name(s)
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
Other Intervention Name(s)
Truvada
Intervention Description
FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet QD
Intervention Type
Drug
Intervention Name(s)
Entecavir (ETV)
Other Intervention Name(s)
Baraclude
Intervention Description
0.5-mg or 1-mg tablet QD
Intervention Type
Drug
Intervention Name(s)
TDF placebo
Intervention Description
Placebo to match TDF QD
Intervention Type
Drug
Intervention Name(s)
FTC/TDF placebo
Intervention Description
Placebo to match FTC/TDF QD
Intervention Type
Drug
Intervention Name(s)
ETV placebo
Intervention Description
Placebo to match ETV QD
Primary Outcome Measure Information:
Title
Percent Probability of Tolerability Failure
Description
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
Title
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
Description
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
Secondary Outcome Measure Information:
Title
Median Time-averaged Change (DAVG) in Plasma Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels at 48 Weeks Relative to Baseline
Description
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
Title
Median DAVG in Plasma HBV DNA Levels at 96 Weeks Relative to Baseline
Description
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
Title
Median DAVG in Plasma HBV DNA Levels at 144 Weeks Relative to Baseline
Description
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
Title
Median DAVG in Plasma HBV DNA Levels at 168 Weeks Relative to Baseline
Description
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
Title
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48
Description
The percentage of participants with plasma HBV DNA < 400 copies/mL at Week 48 was summarized.
Time Frame
Week 48
Title
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 96
Description
The percentage of participants with plasma HBV DNA < 400 copies/mL at Week 96 was summarized.
Time Frame
Week 96
Title
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 144
Description
The percentage of participants with plasma HBV DNA < 400 copies/mL at Week 144 was summarized.
Time Frame
Week 144
Title
Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168
Description
The percentage of participants with plasma HBV DNA < 400 copies/mL at Week 168 was summarized.
Time Frame
Week 168
Title
Percentage of Participants With Normalized Alanine Aminotransferase (ALT) (for Subjects With Elevated ALT at Baseline) at Week 48
Description
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
Title
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 96
Description
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
Title
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 144
Description
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
Title
Percentage of Participants With Normalized ALT (for Subjects With Elevated ALT at Baseline) at Week 168
Description
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
Title
Percentage of Participants With an Increase in Child-Pugh Turcotte (CPT) Score of ≥ 2 Points at Weeks 48
Description
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
Title
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 96
Description
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
Title
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 144
Description
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
Title
Percentage of Participants With an Increase in CPT Score of ≥ 2 Points at Week 168
Description
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
Title
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 48
Description
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
Title
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 96
Description
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
Title
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 144
Description
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
Title
Percentage of Participants With a Decrease in CPT Score of ≥ 2 Points From Baseline at Week 168
Description
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
Title
Median Change in Model for End-Stage Liver Disease (MELD) Score From Baseline at Week 48
Description
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
Title
Median Change in MELD Score From Baseline at Week 96
Description
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
Title
Median Change in MELD Score From Baseline at Week 144
Description
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
Title
Median Change in MELD Score From Baseline at Week 168
Description
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
Title
Percentage of Participants With Hepatitis B Early Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 48 (for Participants Who Were HBeAg Positive at Baseline)
Description
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
Title
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 96 (for Participants Who Were HBeAg Positive at Baseline)
Description
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
Title
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 144 (for Participants Who Were HBeAg Positive at Baseline)
Description
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
Title
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 168 (for Participants Who Were HBeAg Positive at Baseline)
Description
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
Title
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 48
Description
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
Title
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 96
Description
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
Title
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 144
Description
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
Title
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 168
Description
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
Title
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
Other Pre-specified Outcome Measures:
Title
Percentage of Participants With Only Baseline Adefovir Dipivoxil Resistance (ADV-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
Description
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
Title
Percentage of Participants With Only Baseline Lamivudine-resistance (LAM-R) Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
Description
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
Title
Percentage of Participants With Baseline ADV-R + LAM-R Mutations Achieving HBV DNA < 400 Copies/mL by 168 Weeks
Description
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
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:
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 exclusion criteria could not be enrolled in the study:
Pregnant women, women who were breastfeeding or who believed they may have wished to become pregnant during the course of the study
Males and females of reproductive potential who were unwilling to use an effective method of contraception during the study
Prior use of TDF or ETV
History of variceal bleeding, hepatorenal syndrome, Grade 3 or 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 60 days of screening
Grade 2 hepatic encephalopathy at screening
History of solid organ or bone marrow transplant
Current use of hepatotoxic drugs, nephrotoxic drugs, or drugs that interfere with renal tubular secretion
Current therapy with immunomodulators (eg, corticosteroids, interleukin-2, etc.) or investigational drugs
Diagnosis of proximal tubulopathy
Use of investigational agent within 30 days prior to screening
Known hypersensitivity to TDF, FTC, ETV, or formulation excipients of any of the study drug products
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Flaherty, PharmD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Pfleger Liver Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
California Pacific Medical Center Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Miami, Center for Liver Diseases
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Rush Presbyterian - St. Luke's Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Henry Ford Hospital and Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mt. Sinai School of Medicine/ Mt. Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia Presbyterian Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Metropolitan Research
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Heritage Medical Research Clinic
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N4N1
Country
Canada
Facility Name
Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z1H2
Country
Canada
Facility Name
The Gordon & Leslie Diamond Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z3M9
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Hopital Conception
City
Marseille
ZIP/Postal Code
13005
Country
France
Facility Name
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Universitat Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Johannes Gutenberg-Universitat
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
General Hospital of Athens "Ippokratio"
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Universita de Padova
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Policlinico Universitario
City
Udine
ZIP/Postal Code
33100
Country
Italy
Facility Name
Wojewodzki Szpital Specjalistyczny im Dluskeigo
City
Bialystok
ZIP/Postal Code
15-540
Country
Poland
Facility Name
Wojewodzki Szpital Obserwacy
City
Bydgoszcz
ZIP/Postal Code
85-030
Country
Poland
Facility Name
Wojewodzki Szpital Zakazny
City
Warsaw
ZIP/Postal Code
01-201
Country
Poland
Facility Name
National University Hospital Dept. of Gastroenterology & Hepatology
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Tan Tock Seng Hospital
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
Facility Name
Changi General Hospital
City
Singapore
ZIP/Postal Code
529889
Country
Singapore
Facility Name
Hospital General Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic i Provincial de Barcelona (HCPB)
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario de Bellvitge
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital General Universitario Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Universitario y Politecnico la Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Chang Gung Memorial Hospital - Kaohsiung
City
Kaoshiung Hsien
ZIP/Postal Code
833
Country
Taiwan
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
70428
Country
Taiwan
Facility Name
Chang-Gung Memorial Hospital
City
Taipei City
ZIP/Postal Code
114
Country
Taiwan
Facility Name
Cathay General Hospital
City
Taipei
ZIP/Postal Code
10650
Country
Taiwan
Facility Name
Marmara Universitesi School of Medicine
City
Istanbul
ZIP/Postal Code
34899
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi Hastanesi
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
12. IPD Sharing Statement
Citations:
PubMed Identifier
21254162
Citation
Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F, Chang TT, Horban A, Wang C, Kwan P, Buti M, Prieto M, Berg T, Kitrinos K, Peschell K, Mondou E, Frederick D, Rousseau F, Schiff ER. Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology. 2011 Jan;53(1):62-72. doi: 10.1002/hep.23952. Epub 2010 Oct 27.
Results Reference
result
Learn more about this trial
Study Comparing Tenofovir Disoproxil Fumarate (TDF), Emtricitabine (FTC)/TDF, and Entecavir (ETV) in the Treatment of Chronic HBV in Subjects With Decompensated Liver Disease.
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