Hepatitis B, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine
Interventions
DRUGEntecavir
Tablets, Oral, 1mg, once daily, 100 weeks
DRUGTenofovir
Tablets, Oral, 300 mg, once daily
DRUGAdefovir
Tablets, Oral, 10mg, once daily, 100 weeks
DRUGLamivudine
Tablets, Oral, 100mg, once daily, 100 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of lamivudine (LVD) resistance * Subjects must have a history of previous LVD treatment at screening, and must have evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at reverse transcriptase codon 204 (M204V/I/S) * Nucleoside- and nucleotide-naive, except for LVD, and had chronic hepatitis B (HBV) infection * Compensated liver function and must have met ALL of the following criteria:International normalization ratio (INR) ≤ 1.5; Serum albumin ≥ 3 g/dL (≥ 30 g/L); Serum total bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L) * HBV DNA \> 1.72 x 10\*4\* IU/mL (approximately 10\*5\* copies/mL) * Documentation of hepatitis B e antigen (HBeAg) positive and hepatitis B e antibody (HBeAb) negative status at screening * alanine aminotransferase (ALT) ≤ 10 \* upper limit of normal (ULN) at screening * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized * WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Post menopausal is defined as: * Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential * WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 72 hours prior to the start of investigational product
Exclusion criteria
* Evidence of decompensated cirrhosis * Coinfection with human immunodeficiency virus, hepatitis C virus , or hepatitis D virus * Women who are pregnant or breastfeeding * Sexually active fertile men not using effective birth control if their partners were WOCBP * Laboratory values out of protocol-specified range
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48 | Week 48 | HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (\<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA \<50 IU/mL; N = number of participants analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48 | Week 48 | HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. 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. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed. |
| Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96 | Week 96 | HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. 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. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed. |
| Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48 | Week 48 | HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. 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. |
| Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96 | Week 96 | HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOD is the lowest amount or concentration of analyte in a sample, which can be reliably detected, but not necessarily quantified. |
| Percentage of Participants With HBV DNA by PCR Category at Week 48 | Week 48 | HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. |
| Percentage of Participants With HBV DNA by PCR Category at Week 96 | Week 96 | HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. |
| Change in Mean log10 From Baseline in HBV DNA at Week 48 | Baseline, Week 48 | HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load, negative values means reduction. |
| Change in Mean log10 From Baseline in HBV DNA at Week 96 | Baseline, Week 96 | HBV DNA was analyzed by PCR, using the Roche COBAS® TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load. |
| Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48 | Week 48 | ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 or 48 U/L. |
| Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96 | Baseline, Week 96 | ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 U/L. |
| Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only) | Week 48 | HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week |
| Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96 | Week 96 | HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. HBV DNA \< 50 IU/mL = approximately 300 copies/mL. Percentage n/N: n= number of participants with HBV DNA \<50 IU/mL; N = number of participants analyzed. |
| Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only) | Week 48 | HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb). |
| Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only) | Week 96 | HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb). |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 | Week 48 | HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week. |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96 | Week 96 | HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week. |
| Percentage of Participants With HBsAg Seroconversion at Week 48 | Week 48 | HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb. |
| Percentage of Participants With HBsAg Seroconversion at Week 96 | Week 96 | HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb. |
| Cumulative Probability of Emergent Genotypic Resistance at Year 1 | Year 1 | yr=year. Cumulative probability (CP): Ptotal=1-(1-Pyr1)\*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An event is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only). |
| Cumulative Probability of Emergent Genotypic Resistance at Year 2 | Year 2 | Cumulative probability (CP): Ptotal=1-(1-Pyr1)\*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An event is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only). |
| Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | From start of study therapy through Week 100 + 5 days | 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. Grade 1 = mild, Grade 2= moderate, Grade 3 = severe, Grade 4 = life threatening/disabling, Grade 5 = death. |
| Number of Participants With Laboratory Abnormalities: Hematology | From start of study through Week 100 + 5 days | Criteria for hematology abnormalities were: Hemoglobin: \<=11.0 g/dL; White Blood Cells: \<4000/mm\^3; Absolute Neutrophils (includes absolute bands): \<1500/mm\^3; Platelets: \<=99,000/mm\^3; International Normalized Ratio: ≥ 1.5 and ≥ 0.5 from baseline. |
| Number of Participants With Laboratory Abnormalities: Serum Chemistry | On treatment : Day 1 through Week 100 + 5 days; Offtreatment = End of OT period through 24 weeks | ULN=upper limit of normal (Normal ranges are Central lab data and vary according to the site). ALT:\>1.25\*ULN, AST:\>1.25\*ULN, ALP:\>1.25\*ULN, Total Bilirubin:\>1.1\*ULN, Serum Lipase:\>1.10\*ULN, Creatinine:\>1.1\*ULN, Blood Urea Nitrogen:1.25\*ULN, Hyperglycemia:\>116 mg/dL, Hypoglycemia:\<64 mg/dL, Hyponatremia:\<132meq/L, Hypokalemia:\<3.4 meq/L, Albumin:≥1g/dL decrease from baseline, \<3 g/dL; Hypernatremia:\>148 meq/L, Hyperkalemia:\>5.6 meq/L, Hypokalemia:\<3.4 meq/L, Hyperchloremia:\>113 meq/L, Hypochloremia:\<93 meq/L; ALT flare: on treatment (OT), \>2\*Baseline and \>10\*ULN; off treatment (OF), 2\*end of dosing value and \>10\*ULN |
| Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only) | Week 96 | HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week |
Countries
Australia, Brazil, Canada, Greece, Hong Kong, India, Indonesia, Italy, Malaysia, Philippines, Poland, Russia, Singapore, South Korea, Taiwan, Thailand, Turkey (Türkiye), United States
Participant flow
Recruitment details
A total of 629 participants were enrolled at 60 sites.
Pre-assignment details
Of the 629 participants enrolled, 416 were randomized (195 no longer met study criteria, 9 withdrew consent, and 9 had other reason). One participant randomized to entecavir + adefovir (ADV+LVD) Arm withdrew consent before treatment.
Participants by arm
| Arm | Count |
|---|---|
| Entecavir + Adefovir (ETV+ADV) Combination Therapy ETV 1.0 mg + ADV 10 mg; Combination therapy given once daily (QD) for 100 weeks | 138 |
| Entecavir (ETV) Monotherapy ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees. | 140 |
| Adefovir + Lamivudine (ADV+LVD) Combination Therapy ADV 10 mg + LVD 100 mg; Combination therapy given QD for 100 weeks | 137 |
| Total | 415 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Off-treatment Follow up | Continuing off-treatment follow up | 10 | 8 | 11 |
| Off-treatment Follow up | Follow up not required per protocol | 3 | 0 | 1 |
| Off-treatment Follow up | Lost to Follow-up | 1 | 0 | 0 |
| On-Treatment | Adverse Event | 1 | 3 | 2 |
| On-Treatment | Continuing treatment | 69 | 71 | 66 |
| On-Treatment | Death | 1 | 0 | 0 |
| On-Treatment | Lack of Efficacy | 1 | 4 | 0 |
| On-Treatment | Lost to Follow-up | 1 | 0 | 1 |
| On-Treatment | Other Reason | 0 | 0 | 1 |
| On-Treatment | Withdrawal by Subject | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Adefovir + Lamivudine (ADV+LVD) Combination Therapy | Entecavir (ETV) Monotherapy | Entecavir + Adefovir (ETV+ADV) Combination Therapy |
|---|---|---|---|---|
| Age Continuous | 45.0 years | 43.0 years | 43.5 years | 46.0 years |
| Alanine Aminotransferase (ALT) | 47 U/L | 45 U/L | 50 U/L | 49 U/L |
| Albumin | 4.5 g/dL | 4.5 g/dL | 4.5 g/dL | 4.4 g/dL |
| Hepatitis B e antibody (HBeAb) at baseline Negative | 412 participants | 135 participants | 139 participants | 138 participants |
| Hepatitis B e antibody (HBeAb) at baseline Positive | 3 participants | 2 participants | 1 participants | 0 participants |
| Hepatitis B e antigen (HBeAg) status at baseline Negative | 3 participants | 2 participants | 1 participants | 0 participants |
| Hepatitis B e antigen (HBeAg) status at baseline Positive | 412 participants | 135 participants | 139 participants | 138 participants |
| Hepatitis B surface antigen (HBsAg) status at baseline Negative | 0 participants | 0 participants | 0 participants | 0 participants |
| Hepatitis B surface antigen (HBsAg) status at baseline Positive | 415 participants | 137 participants | 140 participants | 138 participants |
| International Normalization Ratio | 1.07 ratio | 1.05 ratio | 1.07 ratio | 1.07 ratio |
| log10 HBV DNA by PCR | 7.6 IU/mL | 7.6 IU/mL | 7.5 IU/mL | 7.6 IU/mL |
| LVD-Resistance Substitution Absent | 8 participants | 3 participants | 3 participants | 2 participants |
| LVD-Resistance Substitution Present | 407 participants | 134 participants | 137 participants | 136 participants |
| Race/Ethnicity, Customized Asian | 389 participants | 126 participants | 131 participants | 132 participants |
| Race/Ethnicity, Customized White | 26 participants | 11 participants | 9 participants | 6 participants |
| Region of Enrollment Australia | 2 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Canada | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Hong Kong | 17 participants | 5 participants | 7 participants | 5 participants |
| Region of Enrollment India | 12 participants | 5 participants | 3 participants | 4 participants |
| Region of Enrollment Indonesia | 1 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment Italy | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Korea, Republic of | 315 participants | 102 participants | 105 participants | 108 participants |
| Region of Enrollment Malaysia | 5 participants | 2 participants | 0 participants | 3 participants |
| Region of Enrollment Philippines | 2 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Poland | 23 participants | 9 participants | 9 participants | 5 participants |
| Region of Enrollment Russian Federation | 2 participants | 2 participants | 0 participants | 0 participants |
| Region of Enrollment Singapore | 2 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Taiwan | 26 participants | 9 participants | 9 participants | 8 participants |
| Region of Enrollment Thailand | 5 participants | 1 participants | 3 participants | 1 participants |
| Region of Enrollment Turkey | 1 participants | 0 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 139 Participants | 40 Participants | 52 Participants | 47 Participants |
| Sex: Female, Male Male | 276 Participants | 97 Participants | 88 Participants | 91 Participants |
| Total Bilirubin | 0.6 mg/dL | 0.6 mg/dL | 0.6 mg/dL | 0.6 mg/dL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 62 / 137 | 75 / 140 | 63 / 138 |
| serious Total, serious adverse events | 13 / 137 | 21 / 140 | 14 / 138 |
Outcome results
Primary
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (\<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA \<50 IU/mL; N = number of participants analyzed.
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48 | 25.4 percentage of participants |
| ETV Monotherapy | Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48 | 16.4 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48 | 19.7 percentage of participants |
p-value: 0.133695% CI: [-2, 19.9]Hochberg procedure
p-value: 0.261995% CI: [-4.2, 15.5]Hochberg procedure
Secondary
Change in Mean log10 From Baseline in HBV DNA at Week 48
HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load, negative values means reduction.
Time frame: Baseline, Week 48
Population: Participants who received at least 1 dose of study therapy and had both baseline and post-baseline values. n=participants with baseline and Week 48 values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETV+ADV Combination Therapy | Change in Mean log10 From Baseline in HBV DNA at Week 48 | HBV DNA at Week 48 | 2.79 log10 (IU/mL | Standard Error 0.093 |
| ETV+ADV Combination Therapy | Change in Mean log10 From Baseline in HBV DNA at Week 48 | Change from baseline | -4.65 log10 (IU/mL | Standard Error 0.077 |
| ETV Monotherapy | Change in Mean log10 From Baseline in HBV DNA at Week 48 | HBV DNA at Week 48 | 4.01 log10 (IU/mL | Standard Error 0.128 |
| ETV Monotherapy | Change in Mean log10 From Baseline in HBV DNA at Week 48 | Change from baseline | -3.35 log10 (IU/mL | Standard Error 0.117 |
| ADV+LVD Combination Therapy | Change in Mean log10 From Baseline in HBV DNA at Week 48 | HBV DNA at Week 48 | 3.36 log10 (IU/mL | Standard Error 0.111 |
| ADV+LVD Combination Therapy | Change in Mean log10 From Baseline in HBV DNA at Week 48 | Change from baseline | -4.11 log10 (IU/mL | Standard Error 0.108 |
95% CI: [-1.534, -0.994]Regression, Linear
95% CI: [-0.824, -0.281]Regression, Linear
Secondary
Change in Mean log10 From Baseline in HBV DNA at Week 96
HBV DNA was analyzed by PCR, using the Roche COBAS® TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load.
Time frame: Baseline, Week 96
Population: Participants who received at least 1 dose of study therapy and had both baseline and post-baseline values were analyzed. n= participants with baseline and Week 96 values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETV+ADV Combination Therapy | Change in Mean log10 From Baseline in HBV DNA at Week 96 | -5.06 participants | Standard Error 0.09 |
| ETV Monotherapy | Change in Mean log10 From Baseline in HBV DNA at Week 96 | -4.17 participants | Standard Error 0.163 |
| ADV+LVD Combination Therapy | Change in Mean log10 From Baseline in HBV DNA at Week 96 | -4.49 participants | Standard Error 0.116 |
Secondary
Cumulative Probability of Emergent Genotypic Resistance at Year 1
yr=year. Cumulative probability (CP): Ptotal=1-(1-Pyr1)\*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An event is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only).
Time frame: Year 1
Population: Treated participants who were tested for resistance, ie. met the following selection criteria. 1) participants with HBV DNA ≥ 50 IU/mL at Week 48 or at the last on-treatment visit and 2) who developed VBT . n=participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr : n=134, 134, 134 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ADVr /TDFr : n=137, 137, 135 | 0.7 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr or TDFr/ADVr : n=133, 132, 132 | 0.8 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr and TDFr/ADVr : n=138, 139, 137 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr with VBT: n=134, 134, 134 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ADVr /TDFr with VBT: n=137, 137, 135 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr or ADVr/TDFr with VBT: n=133, 132, 132 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr and ADVr/TDFr with VBT: n=138, 139, 137 | 0 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr or TDFr/ADVr : n=133, 132, 132 | 3.8 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr or ADVr/TDFr with VBT: n=133, 132, 132 | 0.8 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr and TDFr/ADVr : n=138, 139, 137 | 0 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr with VBT: n=134, 134, 134 | 0.7 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ADVr /TDFr with VBT: n=137, 137, 135 | 0 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr : n=134, 134, 134 | 3 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ADVr /TDFr : n=137, 137, 135 | 0.7 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr and ADVr/TDFr with VBT: n=138, 139, 137 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr or TDFr/ADVr : n=133, 132, 132 | 2.3 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ADVr /TDFr : n=137, 137, 135 | 1.5 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr : n=134, 134, 134 | 0.7 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr and TDFr/ADVr : n=138, 139, 137 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr or ADVr/TDFr with VBT: n=133, 132, 132 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ADVr /TDFr with VBT: n=137, 137, 135 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr with VBT: n=134, 134, 134 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 1 | ETVr and ADVr/TDFr with VBT: n=138, 139, 137 | 0 percentage of participants |
Secondary
Cumulative Probability of Emergent Genotypic Resistance at Year 2
Cumulative probability (CP): Ptotal=1-(1-Pyr1)\*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An event is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only).
Time frame: Year 2
Population: Treated participants who were tested for resistance were analyzed, ie. They met the following selection criteria: 1) participants with HBV DNA ≥ 50 IU/mL at Week 96 or at the last on-treatment visit and 2) who developed VBT. n=participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr with VBT: n=130, 128, 131 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ADVr/TDFr : n=132, 134, 131 | 0.7 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr or ADVr/TDFr with VBT: n=128, 125, 127 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ADVr/TDFr with VBT: n=132, 134, 131 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr : n=130, 128, 131 | 0.8 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr and ADVr/TDFr : n=134, 137, 135 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr or ADVr/TDFr : n=128, 125, 127 | 1.5 percentage of participants |
| ETV+ADV Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr and ADVr/TDFr with VBT: n=134, 137, 135 | 0 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ADVr/TDFr with VBT: n=132, 134, 131 | 0.7 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr or ADVr/TDFr : n=128, 125, 127 | 10.7 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr and ADVr/TDFr : n=134, 137, 135 | 0.7 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr with VBT: n=130, 128, 131 | 6.2 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ADVr/TDFr : n=132, 134, 131 | 1.5 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr or ADVr/TDFr with VBT: n=128, 125, 127 | 6.3 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr and ADVr/TDFr with VBT: n=134, 137, 135 | 0.7 percentage of participants |
| ETV Monotherapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr : n=130, 128, 131 | 9.8 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr or ADVr/TDFr with VBT: n=128, 125, 127 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr and ADVr/TDFr : n=134, 137, 135 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr : n=130, 128, 131 | 1.5 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr and ADVr/TDFr with VBT: n=134, 137, 135 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr or ADVr/TDFr : n=128, 125, 127 | 3.8 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ADVr/TDFr with VBT: n=132, 134, 131 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ETVr with VBT: n=130, 128, 131 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Cumulative Probability of Emergent Genotypic Resistance at Year 2 | ADVr/TDFr : n=132, 134, 131 | 2.2 percentage of participants |
Secondary
Number of Participants With Laboratory Abnormalities: Hematology
Criteria for hematology abnormalities were: Hemoglobin: \<=11.0 g/dL; White Blood Cells: \<4000/mm\^3; Absolute Neutrophils (includes absolute bands): \<1500/mm\^3; Platelets: \<=99,000/mm\^3; International Normalized Ratio: ≥ 1.5 and ≥ 0.5 from baseline.
Time frame: From start of study through Week 100 + 5 days
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | Platelets | 13 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | Neutrophils | 14 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | Hemoglobin | 8 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | White Blood Cells | 53 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | International Normalized Ratio | 8 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Hematology | Neutrophils | 17 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Hematology | Hemoglobin | 9 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Hematology | White Blood Cells | 48 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Hematology | Platelets | 14 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Hematology | International Normalized Ratio | 7 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | International Normalized Ratio | 9 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | Platelets | 12 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | Hemoglobin | 11 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | Neutrophils | 15 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Hematology | White Blood Cells | 38 participants |
Secondary
Number of Participants With Laboratory Abnormalities: Serum Chemistry
ULN=upper limit of normal (Normal ranges are Central lab data and vary according to the site). ALT:\>1.25\*ULN, AST:\>1.25\*ULN, ALP:\>1.25\*ULN, Total Bilirubin:\>1.1\*ULN, Serum Lipase:\>1.10\*ULN, Creatinine:\>1.1\*ULN, Blood Urea Nitrogen:1.25\*ULN, Hyperglycemia:\>116 mg/dL, Hypoglycemia:\<64 mg/dL, Hyponatremia:\<132meq/L, Hypokalemia:\<3.4 meq/L, Albumin:≥1g/dL decrease from baseline, \<3 g/dL; Hypernatremia:\>148 meq/L, Hyperkalemia:\>5.6 meq/L, Hypokalemia:\<3.4 meq/L, Hyperchloremia:\>113 meq/L, Hypochloremia:\<93 meq/L; ALT flare: on treatment (OT), \>2\*Baseline and \>10\*ULN; off treatment (OF), 2\*end of dosing value and \>10\*ULN
Time frame: On treatment : Day 1 through Week 100 + 5 days; Offtreatment = End of OT period through 24 weeks
Population: All treated participants. n = number of participants in the OF period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | ALT flare - Ontreatment | 3 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperkalemia | 3 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Blood Urea Nitrogen | 0 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Alkaline Phosphatase (ALP) | 8 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyponatremia | 0 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperglycemia | 39 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | ALT flare - Offtreatment | 0 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypernatremia | 10 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypoglycemia | 9 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypochloremia | 1 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Albumin | 1 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Aspartate aminotransferase (AST) | 60 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperchloremia | 1 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Serum Lipase | 24 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Alanine aminotransferase (ALT) | 76 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypokalemia | 4 participants |
| ETV+ADV Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Creatinine | 2 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypokalemia | 2 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Alanine aminotransferase (ALT) | 83 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Aspartate aminotransferase (AST) | 62 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Alkaline Phosphatase (ALP) | 4 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Albumin | 1 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Serum Lipase | 33 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Creatinine | 2 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Blood Urea Nitrogen | 1 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperglycemia | 46 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypoglycemia | 5 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypernatremia | 10 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyponatremia | 0 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperkalemia | 4 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperchloremia | 1 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypochloremia | 0 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | ALT flare - Ontreatment | 2 participants |
| ETV Monotherapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | ALT flare - Offtreatment | 0 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Creatinine | 4 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Aspartate aminotransferase (AST) | 53 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperkalemia | 5 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Serum Lipase | 24 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | ALT flare - Ontreatment | 2 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypokalemia | 2 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Albumin | 1 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | ALT flare - Offtreatment | 0 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperchloremia | 1 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Alkaline Phosphatase (ALP) | 6 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypoglycemia | 9 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyperglycemia | 37 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Alanine aminotransferase (ALT) | 74 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypernatremia | 10 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Blood Urea Nitrogen | 2 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hypochloremia | 0 participants |
| ADV+LVD Combination Therapy | Number of Participants With Laboratory Abnormalities: Serum Chemistry | Hyponatremia | 0 participants |
Secondary
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
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. Grade 1 = mild, Grade 2= moderate, Grade 3 = severe, Grade 4 = life threatening/disabling, Grade 5 = death.
Time frame: From start of study therapy through Week 100 + 5 days
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ETV+ADV Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Deaths | 0 participants |
| ETV+ADV Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | SAEs | 11 participants |
| ETV+ADV Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Discontinuations due to AEs | 1 participants |
| ETV+ADV Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | AEs | 101 participants |
| ETV+ADV Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Grade 2-4 Related AEs | 2 participants |
| ETV+ADV Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Grade 3-4 Related AEs | 5 participants |
| ETV Monotherapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Grade 3-4 Related AEs | 7 participants |
| ETV Monotherapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Deaths | 0 participants |
| ETV Monotherapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | AEs | 109 participants |
| ETV Monotherapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Grade 2-4 Related AEs | 12 participants |
| ETV Monotherapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | SAEs | 17 participants |
| ETV Monotherapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Discontinuations due to AEs | 2 participants |
| ADV+LVD Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | SAEs | 12 participants |
| ADV+LVD Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Discontinuations due to AEs | 2 participants |
| ADV+LVD Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Grade 3-4 Related AEs | 9 participants |
| ADV+LVD Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | AEs | 92 participants |
| ADV+LVD Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Deaths | 1 participants |
| ADV+LVD Combination Therapy | Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment | Grade 2-4 Related AEs | 1 participants |
Secondary
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. 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.
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48 | 20.3 percentage of participants |
| ETV Monotherapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48 | 11.4 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48 | 11.7 percentage of participants |
95% CI: [0.3, 17.4]
95% CI: [-0.1, 17.3]
Secondary
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOD is the lowest amount or concentration of analyte in a sample, which can be reliably detected, but not necessarily quantified.
Time frame: Week 96
Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96 | 33.3 percentage of participants |
| ETV Monotherapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96 | 27.1 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96 | 20.4 percentage of participants |
95% CI: [2.4, 23.4]
Secondary
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. 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. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed.
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48 | 25.4 percentage of participants |
| ETV Monotherapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48 | 13.6 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48 | 16.8 percentage of participants |
95% CI: [2.5, 21.1]
95% CI: [-1.1, 18.2]
Secondary
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. 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. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed.
Time frame: Week 96
Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96 | 38.4 Percentage of participants |
| ETV Monotherapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96 | 36.4 Percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96 | 25.5 Percentage of participants |
95% CI: [1.8, 23.9]
Secondary
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48
ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 or 48 U/L.
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy and had ALT \> 1 x ULN at baseline (day 1). Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48 | 75.6 percentage of participants |
| ETV Monotherapy | Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48 | 78.0 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48 | 76.8 percentage of participants |
95% CI: [-15.5, 10.7]
95% CI: [-15, 12.6]
Secondary
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96
ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 U/L.
Time frame: Baseline, Week 96
Population: Participants who received at least 1 dose of study therapy and had ALT \> 1 x ULN at baseline (day 1) were analyzed. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96 | 76.9 percentage of participants |
| ETV Monotherapy | Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96 | 74.4 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96 | 79.7 percentage of participants |
95% CI: [-16.2, 10.6]
Secondary
Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only)
HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only) | 7.2 percentage of participants |
| ETV Monotherapy | Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only) | 6.5 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only) | 5.9 percentage of participants |
95% CI: [-5.2, 6.7]
95% CI: [-4.6, 7.2]
Secondary
Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only)
HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Time frame: Week 96
Population: Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only) | 12.3 percentage of participants |
| ETV Monotherapy | Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only) | 10.7 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only) | 13.9 percentage of participants |
95% CI: [-9.5, 6.4]
Secondary
Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only)
HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only) | 5.1 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only) | 2.9 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only) | 3.7 percentage of participants |
95% CI: [-2.4, 6.8]
95% CI: [-3.5, 6.2]
Secondary
Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only)
HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Time frame: Week 96
Population: Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only) | 7.2 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only) | 3.6 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only) | 5.1 percentage of participants |
95% CI: [-3.6, 7.8]
Secondary
Percentage of Participants With HBsAg Seroconversion at Week 48
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With HBsAg Seroconversion at Week 48 | 0.7 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBsAg Seroconversion at Week 48 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBsAg Seroconversion at Week 48 | 0 percentage of participants |
95% CI: [-0.7, 2.1]
95% CI: [-0.7, 2.1]
Secondary
Percentage of Participants With HBsAg Seroconversion at Week 96
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Time frame: Week 96
Population: Participants who received at least 1 dose of study therapy were analyzed. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With HBsAg Seroconversion at Week 96 | 0 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBsAg Seroconversion at Week 96 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBsAg Seroconversion at Week 96 | 0 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. HBV DNA \< 50 IU/mL = approximately 300 copies/mL. Percentage n/N: n= number of participants with HBV DNA \<50 IU/mL; N = number of participants analyzed.
Time frame: Week 96
Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96 | 43.5 Percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96 | 39.3 Percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96 | 28.5 Percentage of participants |
p-value: 0.009595% CI: [3.7, 26.4]Hochberg procedure
Secondary
Percentage of Participants With HBV DNA by PCR Category at Week 48
HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay.
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 50 to < 172 | 8.0 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | < LOQ (29 IU/mL) | 25.4 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 172 to < 1,720 | 26.1 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | Missing | 3.6 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | LOQ to < 50 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 1,720 to < 17,200 | 28.3 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | >= 172,000 | 0.7 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 17,200 to < 172,000 | 8.0 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | LOQ to < 50 | 2.9 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 17,200 to < 172,000 | 25.7 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | < LOQ (29 IU/mL) | 13.6 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | >= 172,000 | 23.6 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | Missing | 1.4 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 50 to < 172 | 2.9 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 172 to < 1,720 | 7.9 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 1,720 to < 17,200 | 22.1 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | Missing | 1.5 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | < LOQ (29 IU/mL) | 16.8 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | LOQ to < 50 | 2.9 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 50 to < 172 | 5.8 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 172 to < 1,720 | 12.4 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 1,720 to < 17,200 | 31.4 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | 17,200 to < 172,000 | 24.8 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 48 | >= 172,000 | 4.4 percentage of participants |
Secondary
Percentage of Participants With HBV DNA by PCR Category at Week 96
HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay.
Time frame: Week 96
Population: Participants who received at least 1 dose of study therapy were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | < LOQ (29 IU/mL) | 38.4 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | LOQ to < 50 | 5.1 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 50 to < 172 | 10.1 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 172 to < 1,720 | 15.2 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 1,720 to < 17,200 | 20.3 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 17,200 to < 172,000 | 5.8 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | >= 172,000 | 0 percentage of participants |
| ETV+ADV Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | Missing | 5.1 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 50 to < 172 | 3.6 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | >= 172,000 | 16.4 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 172 to < 1,720 | 6.4 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 1,720 to < 17,200 | 10.0 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 17,200 to < 172,000 | 15.7 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | < LOQ (29 IU/mL) | 36.4 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | LOQ to < 50 | 2.9 percentage of participants |
| ETV Monotherapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | Missing | 8.6 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 50 to < 172 | 5.8 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | LOQ to < 50 | 2.9 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | < LOQ (29 IU/mL) | 25.5 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 172 to < 1,720 | 18.2 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | >= 172,000 | 2.9 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 17,200 to < 172,000 | 13.9 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | 1,720 to < 17,200 | 24.8 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With HBV DNA by PCR Category at Week 96 | Missing | 5.8 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Time frame: Week 48
Population: Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 | 0.7 percentage of participants |
| ETV Monotherapy | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 | 0.7 percentage of participants |
95% CI: [-0.7, 2.1]
95% CI: [-2, 2]
Secondary
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96
HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Time frame: Week 96
Population: Participants who received at least 1 dose of study therapy were analyzed. Participants with missing efficacy assessments were considered as a failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETV+ADV Combination Therapy | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96 | 0 percentage of participants |
| ETV Monotherapy | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96 | 0 percentage of participants |
| ADV+LVD Combination Therapy | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96 | 0 percentage of participants |