Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B
- Conditions
- Hepatitis B, Chronic
- Interventions
- Registration Number
- NCT00410072
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to compare the effectiveness of entecavir plus tenofovir combination therapy with that of entecavir monotherapy. Safety will also be studied.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 669
- Chronic hepatitis B virus (HBV) infection (hepatitis B e antigen [HbeAg]-positive or negative) disease
- Nucleoside- and nucleotide-naive
- Males or females ≥16 years of age (or minimum age of consent in a given country)
- Compensated liver function
- HBV DNA >1.72*10*5*IU/mL (approximately 10*6*copies/mL) for HbeAg-positive participants
- HBV DNA >1.72*10*4*IU/mL (approximately 10*5*copies/mL) for Hbe-Ag-negative participants
- Alanine aminotransferase level ≥*upper limit of normal (ULN) and ≤10*ULN
- Evidence of decompensated cirrhosis
- Coinfection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
- Laboratory values out of protocol-specified range
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ETV 0.5 mg +TDF 300 mg Entecavir + Tenofovir ETV=entecavir; TDF=tenofovir TDF 0.5 mg Entecavir TDF=tenofovir
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96 At Week 96 HBV DNA levels \<50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status At Weeks 48 and 96 HBV DNA levels \<50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96 At Weeks 48 and 96 LOQ=lower limit of quantitation. LOQ=29 IU/mL, or approximately 169 copies/mL. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix-, method-, and analyte-specific.Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96 At Weeks 48 and 96 LOD=Lower limit of detection. LOD) LOD=10 IU/mL, or approximately 58 copies/mL. LOD is the lowest concentration level that can be determined to be statistically different from a blank (99% confidence). The LOD is typically determined to be in the region where the signal to noise ratio is greater than 5. Limits of detection are matrix-, method-, and analyte-specific.Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Mean Log 10 HBV DNA at Weeks 48 and 96 Baseline, Weeks 48 and 96 HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan - HPS assay. Reduction in Log 10 HBV count=reduced viral load.
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96 At Weeks 48 and 96 ALT normalization= ≤1\*upper limit of normal (ULN). Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96 At Weeks 48 and 96 HBeAg is a hepatitis B viral protein and is an indicator of active viral replication. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96 At Weeks 48 and 96 HBeAg seroconversion=HBeAg loss and presence of hepatitis B e antibody (HBeAb). HBeAg is a hepatitis B viral protein and is an indicator of active viral replication.
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96 At Weeks 48 and 96 HBsAg = A part of the hepatitis B virus. When found in the blood, HBsAg is an early marker of infection. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96 At Weeks 48 and 96 HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 At Weeks 48 and 96 Using the Roche COBAS TaqMan - HPS assay. Lower limit of Quantitation (LOQ) is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix-, method-, and analyte-specific.
Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities From enrollment through Week 100 + 24-week follow-up AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.
Number of Participants With HBV Resistance Through Week 48 Week 48 ETVr=entecavir resistance; TDFr=tenofovir resistance. HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used.
Number of Participants With HBV Resistance at Week 96 Week 96 ETVr=entecavir resistance; TFDr=tenofovir resistance. HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used.
Number of Participants With Virologic Breakthrough at Week 48 Week 48 ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough= confirmed \>= 1 log10 increase in HBV DNA from the on-treatment nadir
Number of Participants With Virologic Breakthrough at Week 96 Week 96 ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough=confirmed \>=1 log10 increase in HBV DNA from moving nadir
Trial Locations
- Locations (17)
University Of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Sergio E. Rojter
🇺🇸Los Angeles, California, United States
Tuan Nguyen, Md
🇺🇸San Diego, California, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
San Jose Gastroenterology
🇺🇸San Jose, California, United States
University Of Miami
🇺🇸Miami, Florida, United States
Digestive Healthcare Of Georgia
🇺🇸Atlanta, Georgia, United States
Digestive Disease Associates, P.A.
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
North Shore University
🇺🇸Manhasset, New York, United States
Maryland Digestive Disease Research, Llc
🇺🇸Laurel, Maryland, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
Concorde Medical Group
🇺🇸New York, New York, United States
Sing Chan, Md
🇺🇸Flushing, New York, United States
Local Institution
🇹🇷Trabzon, Turkey
Mount Sinai School Of Medicine
🇺🇸New York, New York, United States
Atlanta Gastroenterology Associates
🇺🇸Atlanta, Georgia, United States