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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
669
Tablets, Oral, ETV = 0.5 mg, once daily, 100 weeks
Tablets, Oral, ETV = 0.5 mg + TFV = 300 mg, once daily, 100 weeks
Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) 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.
Time frame: At Week 96
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
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.
Time frame: At Weeks 48 and 96
Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR 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.
Time frame: At Weeks 48 and 96
Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96
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Sergio E. Rojter
Los Angeles, California, United States
Tuan Nguyen, Md
San Diego, California, United States
San Jose Gastroenterology
San Jose, California, United States
Yale University School Of Medicine
New Haven, Connecticut, United States
University Of Miami
Miami, Florida, United States
Atlanta Gastroenterology Associates
Atlanta, Georgia, United States
Digestive Healthcare Of Georgia
Atlanta, Georgia, United States
Digestive Disease Associates, P.A.
Baltimore, Maryland, United States
Maryland Digestive Disease Research, Llc
Laurel, Maryland, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
...and 58 more locations
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.
Time frame: At Weeks 48 and 96
Mean Log 10 HBV DNA at 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.
Time frame: Baseline, Weeks 48 and 96
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization 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.
Time frame: At Weeks 48 and 96
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss 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.
Time frame: At Weeks 48 and 96
Percentage of Participants With HBeAg Seroconversion [( 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.
Time frame: At Weeks 48 and 96
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss 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.
Time frame: At Weeks 48 and 96
Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.
Time frame: At Weeks 48 and 96
Number of Participants With HBV DNA in Relevant Categories 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.
Time frame: At Weeks 48 and 96
Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities
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.
Time frame: From enrollment through Week 100 + 24-week follow-up
Number of Participants With HBV Resistance Through 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.
Time frame: Week 48
Number of Participants With HBV Resistance at 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.
Time frame: Week 96
Number of Participants With Virologic Breakthrough at Week 48
ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough= confirmed \>= 1 log10 increase in HBV DNA from the on-treatment nadir
Time frame: Week 48
Number of Participants With Virologic Breakthrough at Week 96
ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough=confirmed \>=1 log10 increase in HBV DNA from moving nadir
Time frame: Week 96