Chronic Hepatitis B
Conditions
Brief summary
The purpose of this study is to show that the combination of entecavir and tenofovir, is effective and well tolerated in chronic hepatitis B patients who have failed previous treatment.
Interventions
DRUGEntecavir
Tablets, Oral, 1 mg, once daily, 96 weeks
DRUGTenofovir
Tablets, Oral, 300 mg, once daily, 96 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with chronic hepatitis B virus (HBV) infection; either hepatitis B-e antigen(HBeAg)-negative or HBeAg-positive * Subjects must have a treatment failure to their current nucleoside/ nucleotide treatment regimen * Prior entecavir and/or tenofovir monotherapy is allowed * Subjects must have compensated liver function
Exclusion criteria
* Women who are pregnant or breastfeeding * Evidence of decompensated cirrhosis * Co-infection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV) * Moderate or severe renal impairment * Recent history of pancreatitis * Therapy with interferon, thymosin alpha or other immuno-stimulators within 24 weeks of being assigned to study drug into this study * Prior entecavir/tenofovir combination therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Virologic Response at Week 48 - Treated Population | Week 48 | Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population | Baseline to Weeks 12, 24, 48, 96 | HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay. The results were reported in log 10 IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ. Baseline was Day 1, prior to study drug administration. |
| Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population | Weeks 24, 48, 96 | HBV DNA less than (\<) LLD (6 IU/mL) was defined/measured by the COBAS(REGISTERED) TaqMan HPS assay at Weeks 24, 48, and 96. Percentage was calculated as number of participants with HBV DNA \< LLD at Weeks 24, 48, 96 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). |
| Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline | Baseline to Weeks 24, 48, and 96 | Loss of HBeAg was defined as being HBeAg-negative at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline. Method used for HBeAg was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples. Percentage was calculated as number of participants with HBeAg loss at Weeks 24 and 48 divided by the number of treated participants who were HBeAg-positive at baseline. Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug. |
| Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline | Baseline, Weeks 24, 48, and 96 | HBe seroconversion was defined as being both HBeAg-negative and HBeAb-positive at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline. Method used was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples. Percentage was calculated as number of participants with HBe seroconversion at Weeks 24, 48, and 96 divided by the number of treated participants who were HBeAg-positive at baseline. Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug. |
| Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population | Week 24, Week 96 | Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 24, Week 96 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ. |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline | Baseline, Weeks 24, 48, and 96 | HBsAg seroconversion was defined as being both HBsAg-negative and HBsAb-positive at Weeks 24, 48, and 96 in those participants who had been HBsAg-positive at baseline. Percentage was calculated as number of participants with HBs seroconversion at Weeks 24 and 48 divided by the number of treated participants who were HBsAg-positive at baseline. Positive result for HBsAg was one of the inclusion criteria. Treated participants (HBsAg positive at baseline) were evaluated using NC=F. The method used was an Immunoassay testing - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma \[potassium ethylenediaminetetraacetic acid (EDTA), lithium or sodium heparinized\]. Baseline was Day 1, before start of study drug. |
| Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population | Day 1 to last dose of study drug plus 5 days; up to Week 96 | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. On-treatment = on Day 1 through last dose of study therapy + 5 days. |
| Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population | Baseline to Weeks 48, 96 | Testing of HBV genotype was performed at baseline for all treated patients and for participants at Weeks 48 and 96 with primary non-response or virologic breakthrough. Emergent genotypic resistance to study drugs was defined as follows: Emergent = not detected at baseline; entecavir (ETV) resistance (ETVr): participant's sample was to have rtM204V/I/S and any substitution at rtT184, rtS202, or rtM250; tenofovir (TDF) resistance (TDFr) which was based on adefovir (ADV)-mutations: participant's sample was to have rtA181T/V, rtN236T, or (rtA194T and rtM204V/I/S). Primary non-response was defined as \< 1 log10 decrease in HBV DNA from baseline on treatment at or after Week 12. Virologic breakthrough was defined as ≥ 1 log10 increase in HBV DNA over nadir on treatment, either confirmed or last on-treatment followed by discontinuation of study therapy. |
| Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Day 1 to last dose of study drug plus 5 days; up to Week 96 | Selected criteria presented in each category. Upper limit of normal among all laboratory ranges (ULN); Baseline (BL); alanine transaminase (ALT); milligram per deciliter (mg/dL); milliliters per minute (mL/min); greater than (\>);greater than, equal to (\>=); less than (\<). Creatinine data presented below were confirmed, ie, at least 2 consecutive values. On-treatment = after Day 1 through last dose of study therapy + 5 days. |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline | Baseline, Weeks 24, 48, 96 | Loss of HBsAg was defined as being HBsAg-negative at Weeks 24, 48, 96 in those participants who had been HBsAg-positive at baseline. The method used: Immunoassay - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma (potassium ethylene diamine tetraacetic acid, lithium or sodium heparinized). Percentage calculated as number of participants with a HBsAg loss at Weeks 24, 48, and 96 divided by the number of treated participants who were HBsAg-positive at baseline (participants were not enrolled into the study unless they were positive for HBsAg). Treated participants (HBsAg-positive at baseline) were evaluated using NC=F. Baseline was Day 1, before start of study drug. |
Countries
France, Germany, Italy, Netherlands, Poland, Romania, Spain
Participant flow
Recruitment details
Study initiated 17 May 2010; Week 48 Primary Endpoint 27 November 2012; Week 96 Study Completed18 February 2014. Participants with chronic Hepatitis B with surface antigen (HBsAg) who have been currently treated and experienced treatment failure were enrolled.
Pre-assignment details
144 enrolled; 92 treated. Reasons for 52 never treated: physical/laboratory test findings 30; not in target population 21; no signed consent 7; medical history/concurrent disease 2; other exclusion criteria 1; unknown 3.
Participants by arm
| Arm | Count |
|---|---|
| Entecavir + Tenofovir Entecavir (ETV): Tablets, Oral, 1 mg, once daily, 96 weeks
Tenofovir disoproxil fumarate (TDF): Tablets, Oral, 300 mg, once daily, 96 weeks | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Participants Treated With Study Drug | Adverse Event | 1 |
| Participants Treated With Study Drug | Lost to Follow-up | 1 |
| Participants Treated With Study Drug | Pregnancy | 1 |
| Participants Treated With Study Drug | Protocol Violation | 1 |
| Participants Treated With Study Drug | Withdrawal by Subject | 2 |
| Post Dosing Follow-up Through 24 Weeks | Alternative therapy started | 32 |
| Post Dosing Follow-up Through 24 Weeks | Lost to Follow-up | 1 |
| Post Dosing Follow-up Through 24 Weeks | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Entecavir + Tenofovir |
|---|---|
| Age, Continuous | 42.0 years |
| Baseline HBV Subtype HBV Subtype A | 21 Participants |
| Baseline HBV Subtype HBV Subtype B | 2 Participants |
| Baseline HBV Subtype HBV Subtype C | 1 Participants |
| Baseline HBV Subtype HBV Subtype D | 35 Participants |
| Baseline HBV Subtype HBV Subtype E | 4 Participants |
| Baseline HBV Subtype HBV Subtype G | 1 Participants |
| Baseline HBV Subtype HBV Subtype H | 1 Participants |
| Baseline HBV Subtype HBV Subtype Indeterminate | 3 Participants |
| Baseline HBV Subtype Insufficient HBV DNA | 23 Participants |
| Baseline HBV Subtype Missing HBV DNA test | 1 Participants |
| Baseline Hepatitis B e Antibody Intermediate Hepatitis B e antibody | 2 participants |
| Baseline Hepatitis B e Antibody missing Hepatitis B e antibody test | 2 participants |
| Baseline Hepatitis B e Antibody Negative for Hepatitis B e antibody | 56 participants |
| Baseline Hepatitis B e Antibody Positive for Hepatitis B e antibody | 32 participants |
| Baseline Hepatitis B e Antigen missing Hepatitis B e antigen test | 2 participants |
| Baseline Hepatitis B e Antigen Negative for Hepatitis B e antigen | 34 participants |
| Baseline Hepatitis B e Antigen Positive for Hepatitis B e antigen | 56 participants |
| Baseline Hepatitis B Surface Antigen Negative for Hepatitis B Surface Antigen | 0 participants |
| Baseline Hepatitis B Surface Antigen Positive for Hepatitis B Surface Antigen | 92 participants |
| HBV DNA by PCR (log10 IU/mL) | 3.674 log10 IU/mL |
| Region of Enrollment France | 10 participants |
| Region of Enrollment Germany | 23 participants |
| Region of Enrollment Italy | 1 participants |
| Region of Enrollment Netherlands | 6 participants |
| Region of Enrollment Poland | 32 participants |
| Region of Enrollment Romania | 20 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 69 Participants |
| Treatment Failure Prior to Baseline Missing | 1 participants |
| Treatment Failure Prior to Baseline Partial Virological Breakthrough | 52 participants |
| Treatment Failure Prior to Baseline Primary Non-Response | 9 participants |
| Treatment Failure Prior to Baseline Virological Breakthrough | 30 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 92 |
| serious Total, serious adverse events | 6 / 92 |
Outcome results
Primary
Percentage of Participants With a Virologic Response at Week 48 - Treated Population
Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
Time frame: Week 48
Population: All treated participants were analyzed (NC = F). An exact binomial 95% confidence interval was constructed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir + Tenofovir | Percentage of Participants With a Virologic Response at Week 48 - Treated Population | 76.1 percentage of participants |
Secondary
Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population
HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay. The results were reported in log 10 IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ. Baseline was Day 1, prior to study drug administration.
Time frame: Baseline to Weeks 12, 24, 48, 96
Population: All treated participants with results at both baseline and on-treatment were analyzed. n=Number of treated participants with results at baseline and Week 12, Week 24, Week 48 and Week 96.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir + Tenofovir | Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population | Week 24 (n=89) | -2.581 log10 IU/mL | Standard Deviation 1.8019 |
| Entecavir + Tenofovir | Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population | Week 12 (n=89) | -2.230 log10 IU/mL | Standard Deviation 1.5339 |
| Entecavir + Tenofovir | Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population | Week 48 (n=88) | -2.829 log10 IU/mL | Standard Deviation 2.0537 |
| Entecavir + Tenofovir | Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population | Week 96 (n=84) | -2.965 log10 IU/mL | Standard Deviation 2.1431 |
Secondary
Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Selected criteria presented in each category. Upper limit of normal among all laboratory ranges (ULN); Baseline (BL); alanine transaminase (ALT); milligram per deciliter (mg/dL); milliliters per minute (mL/min); greater than (\>);greater than, equal to (\>=); less than (\<). Creatinine data presented below were confirmed, ie, at least 2 consecutive values. On-treatment = after Day 1 through last dose of study therapy + 5 days.
Time frame: Day 1 to last dose of study drug plus 5 days; up to Week 96
Population: N=treated participants with on-treatment laboratory test results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | ALT > 2*Baseline(N=90) | 9 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | ALT > 3*Baseline(N=90) | 2 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Total bilirubin >2*Baseline (N=90) | 11 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Total bilirubin >3*Baseline (N=90) | 3 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Lipase > 3*Baseline (N=90) | 4 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Creatinine increase from BL >= 20%(N=91) | 4 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Creatinine >1.5 mg/dL (N=91) | 2 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Creatinine clearance < 50 mL/min (N=91) | 1 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Phosphate < 2.0 mg/dL (N=90) | 2 participants |
| Entecavir + Tenofovir | Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population | Phosphate < 2.3 mg/dL (N=90) | 8 participants |
Secondary
Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population
Testing of HBV genotype was performed at baseline for all treated patients and for participants at Weeks 48 and 96 with primary non-response or virologic breakthrough. Emergent genotypic resistance to study drugs was defined as follows: Emergent = not detected at baseline; entecavir (ETV) resistance (ETVr): participant's sample was to have rtM204V/I/S and any substitution at rtT184, rtS202, or rtM250; tenofovir (TDF) resistance (TDFr) which was based on adefovir (ADV)-mutations: participant's sample was to have rtA181T/V, rtN236T, or (rtA194T and rtM204V/I/S). Primary non-response was defined as \< 1 log10 decrease in HBV DNA from baseline on treatment at or after Week 12. Virologic breakthrough was defined as ≥ 1 log10 increase in HBV DNA over nadir on treatment, either confirmed or last on-treatment followed by discontinuation of study therapy.
Time frame: Baseline to Weeks 48, 96
Population: All treated participants who met resistance testing criteria (primary non-response or virologic breakthrough) and were tested for resistance to both study drugs were analyzed. n = number of participants analyzed at Weeks 48 and 96.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population | Week 48 (n=5) | 0 participants |
| Entecavir + Tenofovir | Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population | Week 96 (n=7) | 0 participants |
Secondary
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. On-treatment = on Day 1 through last dose of study therapy + 5 days.
Time frame: Day 1 to last dose of study drug plus 5 days; up to Week 96
Population: All Treated participants were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population | Treatment emergent SAE | 6 participants |
| Entecavir + Tenofovir | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population | Discontinuation of treatment due to AE | 1 participants |
Secondary
Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population
Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 24, Week 96 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
Time frame: Week 24, Week 96
Population: All treated participants were analyzed at Weeks 24 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population | Week 24 (n=92) | 64.1 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population | Week 96 (n=92) | 84.8 percentage of participants |
Secondary
Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline
HBe seroconversion was defined as being both HBeAg-negative and HBeAb-positive at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline. Method used was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples. Percentage was calculated as number of participants with HBe seroconversion at Weeks 24, 48, and 96 divided by the number of treated participants who were HBeAg-positive at baseline. Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
Time frame: Baseline, Weeks 24, 48, and 96
Population: All treated participants who were HBeAg-positive at baseline were analyzed at Weeks 24, 48 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline | Week 24 (n=56) | 3.6 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline | Week 48 (n=56) | 3.6 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline | Week 96 (n=56) | 1.8 percentage of participants |
Secondary
Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population
HBV DNA less than (\<) LLD (6 IU/mL) was defined/measured by the COBAS(REGISTERED) TaqMan HPS assay at Weeks 24, 48, and 96. Percentage was calculated as number of participants with HBV DNA \< LLD at Weeks 24, 48, 96 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F).
Time frame: Weeks 24, 48, 96
Population: All treated participants were analyzed at Weeks 24, 48 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population | Week 24 (n=92) | 12.0 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population | Week 48 (n=92) | 18.5 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population | Week 96 (n=92) | 16.3 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline
Loss of HBeAg was defined as being HBeAg-negative at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline. Method used for HBeAg was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples. Percentage was calculated as number of participants with HBeAg loss at Weeks 24 and 48 divided by the number of treated participants who were HBeAg-positive at baseline. Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
Time frame: Baseline to Weeks 24, 48, and 96
Population: All treated participants who were HBeAg-positive at baseline were analyzed at Weeks 24, 48 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline | Week 96 (n=56) | 8.9 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline | Week 24 (n=56) | 3.6 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline | Week 48 (n=56) | 5.4 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline
Loss of HBsAg was defined as being HBsAg-negative at Weeks 24, 48, 96 in those participants who had been HBsAg-positive at baseline. The method used: Immunoassay - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma (potassium ethylene diamine tetraacetic acid, lithium or sodium heparinized). Percentage calculated as number of participants with a HBsAg loss at Weeks 24, 48, and 96 divided by the number of treated participants who were HBsAg-positive at baseline (participants were not enrolled into the study unless they were positive for HBsAg). Treated participants (HBsAg-positive at baseline) were evaluated using NC=F. Baseline was Day 1, before start of study drug.
Time frame: Baseline, Weeks 24, 48, 96
Population: All treated participants who were HBsAg-positive at baseline and were analyzed at Weeks 24, 48, and 96 (NC = F). An exact binomial 95% Confidence Interval was constructed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline | Week 24 (n=92) | 1.1 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline | Week 48 (n=92) | 0 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline | Week 96 (n=92) | 2.2 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline
HBsAg seroconversion was defined as being both HBsAg-negative and HBsAb-positive at Weeks 24, 48, and 96 in those participants who had been HBsAg-positive at baseline. Percentage was calculated as number of participants with HBs seroconversion at Weeks 24 and 48 divided by the number of treated participants who were HBsAg-positive at baseline. Positive result for HBsAg was one of the inclusion criteria. Treated participants (HBsAg positive at baseline) were evaluated using NC=F. The method used was an Immunoassay testing - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma \[potassium ethylenediaminetetraacetic acid (EDTA), lithium or sodium heparinized\]. Baseline was Day 1, before start of study drug.
Time frame: Baseline, Weeks 24, 48, and 96
Population: All treated participants who were HBsAg-positive at baseline and were analyzed at Weeks 24, 48 and 96 (NC = F). An exact binomial 95% confidence interval was constructed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline | Week 24 (n=92) | 1.1 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline | Week 48 (n=92) | 0 percentage of participants |
| Entecavir + Tenofovir | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline | Week 96 (n=92) | 1.1 percentage of participants |