Chronic Hepatitis B
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety following the Roadmap Concept strategy with an initial monotherapy using either telbivudine or tenofovir in HBeAg negative CHB patients. The data from the study should allow for the validation of the Roadmap concept in a prospective manner, for both telbivudine and tenofovir treated HBeAg negative CHB patients. As part of a post-approval commitment to the European Health Authorities, the data will also be used to provide an optimized clinical treatment strategy for better clinical use of telbivudine in European HBeAg negative patients. Furthermore, the data from the study will contribute to a better scientific understanding, disease management and treatment of HBeAg negative CHB patients.
Interventions
DRUGtelbivudine
600 mg film-coated tablets taken as 600 mg once daily
DRUGtenofovir disoproxil fumarate
300 mg tablets taken as 300 mg once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male or female, at least 18 years of age Documented compensated HBeAg negative CHB defined by all of the following: * Detectable serum HBsAg at screening visit and at least 6 months prior; * HBeAg negative at the screening visit with positive HBeAb; * Serum HBV DNA \> 2000 IU/mL Serum ALT level \> 1×ULN and \<10×ULN at screening visit; patient with normal ALT ≤1xULN at screening are eligible, with moderate liver inflammation or fibrosis, complensated liver sirrhosis, ALT level \>1xULN wtihin last 6 months
Exclusion criteria
* Co-infected with HCV, HDV or HIV. * Received treatment of nucleoside or nucleotide drugs at any time * Received IFN or other immunomodulatory treatment within six months before Screening * Pregnant or nursing (lactating) women * Clinical signs/symptoms of hepatic decompensation * History of myopathy, myositis or persistent muscle weakness * history of clinical and laboratory evidence of chronic renal insufficency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | week 52 | The primary objective of the study is to compare the efficacy of Roadmap-Concept-based telbivudine treatment versus Roadmap-Concept-based tenofovir treatment in HBeAg-negative CHB patients. The rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 will be used for the comparison of the efficacy. The hypothesis is that the aggregated rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 of Telbivudine (ARM 1) is non-inferior to Tenofovir (ARM 2). For the treating missing as failure analysis, patients who came for their primary endpoint Week 52 visit within the ± 7-day window but not on the exact designated day of the visit were treated as missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | week 24, 52, 104 | To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA \<300 copies/mL (51 IU/mL), ALT normalization, HBsAg loss, HBsAg conversion, virologic breakthrough (VB) at study visit, cumulative VB by study defined study period, cumulative treatment-emergent resistance |
| Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | 156 weeks | To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA \<300 copies/mL (51 IU/mL) at Week156, ALT normalization, HBsAg loss, development of HBsAg conversion , cumulative tx emergent resistance, HBV DNA \<300 copies/mL with HBV DNA \<7 log at Baseline |
| eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeks | eGFR changes were calculated using the Modification of Diet in Renal Disease (MDRD) formula: GFR = 186 x (sCr)\^(-1.154) x (age)\^-0.203 with Female: Multiply GFR by 0.742; Black: Multiply GFR by 1.210. sCr is Serum Creatinine in mg/dl (measured at each scheduled visit). Age in years at visit (=\[sCr sample collection date -Date of birth\]/365.25). Weight in kilograms, as measured at the visit or the closest previous visit Safety population. |
Countries
Austria, Bulgaria, Germany, Greece, Italy, Russia, Spain, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LdT Mono at Week 24 Patients who had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 continued to receive 600 mg telbivudine daily after Week 24 | 99 |
| LdT+TDF at Week 24 Patients who were initially treated with telbivudine and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 600 mg telbivudine daily and additional 300 mg tenofovir after Week 24. | 22 |
| TDF Mono at Week 24 Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \< 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir daily after Week 24. | 109 |
| TDF + LdT at Week 24 Patients who were initially treated with tenofovir and had hepatitis B virus deoxyribonucleic acid \> 300 copies/mL in their blood at Week 24 and continued to receive 300 mg tenofovir and additional 600 mg telbivudine after Week 24. | 11 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Extension Period Weeks 109-156 | Administrative problems | 3 | 0 | 1 | 0 |
| Extension Period Weeks 109-156 | Lost to Follow-up | 6 | 1 | 5 | 0 |
| Extension Period Weeks 109-156 | Protocol Violation | 2 | 1 | 0 | 0 |
| Extension Period Weeks 109-156 | Withdrawal by Subject | 8 | 1 | 8 | 0 |
| Treatment to Week 104 | Abnormal lab value | 1 | 0 | 0 | 0 |
| Treatment to Week 104 | Abnormal test procedure result(s) | 1 | 0 | 0 | 0 |
| Treatment to Week 104 | Administrative problems | 3 | 1 | 0 | 0 |
| Treatment to Week 104 | Adverse Event | 2 | 0 | 5 | 0 |
| Treatment to Week 104 | Lost to Follow-up | 5 | 0 | 3 | 0 |
| Treatment to Week 104 | Protocol Violation | 1 | 1 | 1 | 0 |
| Treatment to Week 104 | Withdrawal by Subject | 6 | 1 | 4 | 0 |
Baseline characteristics
| Characteristic | LdT Mono at Week 24 | Total | TDF + LdT at Week 24 | TDF Mono at Week 24 | LdT+TDF at Week 24 |
|---|---|---|---|---|---|
| Age, Customized < 30 years | 17 Participants | 39 Participants | 0 Participants | 18 Participants | 4 Participants |
| Age, Customized > 50 years | 26 Participants | 67 Participants | 4 Participants | 32 Participants | 5 Participants |
| Age, Customized Between 30 and 50 years | 56 Participants | 135 Participants | 7 Participants | 59 Participants | 13 Participants |
| HBV DNA | 5.887 log10 copies/mL) STANDARD_DEVIATION 1.2862 | 5.887 log10 copies/mL) STANDARD_DEVIATION 1.2862 | 7.938 log10 copies/mL) STANDARD_DEVIATION 1.0709 | 5.838 log10 copies/mL) STANDARD_DEVIATION 1.2464 | 7.769 log10 copies/mL) STANDARD_DEVIATION 1.2502 |
| HBV DNA levels < or ≥ 7 log 10 copies/mL at baseline. < 7 log 10 copies/mL | 81 Participants | 171 Participants | 3 Participants | 83 Participants | 4 Participants |
| HBV DNA levels < or ≥ 7 log 10 copies/mL at baseline. ≥ 7 log 10 copies/mL | 18 Participants | 70 Participants | 8 Participants | 26 Participants | 18 Participants |
| Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN) > 1 × - < 2 × ULN | 35 Participants | 74 Participants | 5 Participants | 27 Participants | 7 Participants |
| Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN) ≤ 1 × ULN | 46 Participants | 105 Participants | 4 Participants | 52 Participants | 3 Participants |
| Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN) 2 × - < 5 × ULN | 13 Participants | 51 Participants | 1 Participants | 26 Participants | 11 Participants |
| Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN) 5 × or more ULN | 5 Participants | 11 Participants | 1 Participants | 4 Participants | 1 Participants |
| Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN) > 1 × - < 2 × ULN | 14 Participants | 51 Participants | 7 Participants | 23 Participants | 7 Participants |
| Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN) ≤ 1 × ULN | 70 Participants | 151 Participants | 2 Participants | 69 Participants | 10 Participants |
| Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN) 2 × - < 5 × ULN | 12 Participants | 33 Participants | 1 Participants | 16 Participants | 4 Participants |
| Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN) 5 × or more ULN | 3 Participants | 6 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 28 Participants | 73 Participants | 4 Participants | 34 Participants | 7 Participants |
| Sex: Female, Male Male | 71 Participants | 168 Participants | 7 Participants | 75 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 60 / 98 | 15 / 22 | 56 / 109 | 8 / 11 |
| serious Total, serious adverse events | 6 / 98 | 5 / 22 | 11 / 109 | 2 / 11 |
Outcome results
Primary
Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -
The primary objective of the study is to compare the efficacy of Roadmap-Concept-based telbivudine treatment versus Roadmap-Concept-based tenofovir treatment in HBeAg-negative CHB patients. The rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 will be used for the comparison of the efficacy. The hypothesis is that the aggregated rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 of Telbivudine (ARM 1) is non-inferior to Tenofovir (ARM 2). For the treating missing as failure analysis, patients who came for their primary endpoint Week 52 visit within the ± 7-day window but not on the exact designated day of the visit were treated as missing data.
Time frame: week 52
Population: Roadmap intent-to-treat (rITT) population consisted of patients in the ITT population who did not discontinue before Wk 24 and did not receive add-on. The total of the mono and combination arms were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LdT Overall | Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | Imputing +/- 7 days DNA for Wk 52 | 91.9 percentage of participants |
| LdT Overall | Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | Missing DNA data at Wk 52=failure | 91.0 percentage of participants |
| LdT Overall | Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | Imputing LOCF DNA for Wk 52 | 95.4 percentage of participants |
| LdT Overall | Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | Imputing within +28d DNA for Wk 52 | 92.7 percentage of participants |
| TDF Overall | Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | Imputing within +28d DNA for Wk 52 | 95.0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | Imputing LOCF DNA for Wk 52 | 99.2 percentage of participants |
| TDF Overall | Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | Missing DNA data at Wk 52=failure | 95.0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - | Imputing +/- 7 days DNA for Wk 52 | 95.0 percentage of participants |
Comparison: Missing DNA data at Wk 52=failure: To evaluate the primary objective, Mantel-Haenszel weighted estimates approach (stratified by HBV DNA level (\< 7 log10 copies/mL or ≥ 7 log10 copies/mL) and ALT (\< 3×ULN or ≥ 3×ULN) at baseline) was employed to assess the proportion of patients (response rate) who achieve HBV DNA \< 300 copies/mL after 52 weeks treatment in each treatment arm, as well as the difference in proportions (telbivudine - tenofovir arm) and the 95% CI of the difference.95% CI: [-10.5, 2.5]
Comparison: Imputing +/- 7 days DNA for Wk 52: To evaluate the primary objective, Mantel-Haenszel weighted estimates approach (stratified by HBV DNA level (\< 7 log10 copies/mL or ≥ 7 log10 copies/mL) and ALT (\< 3×ULN or ≥ 3×ULN) at baseline) was employed to assess the proportion of patients (response rate) who achieve HBV DNA \< 300 copies/mL after 52 weeks treatment in each treatment arm, as well as the difference in proportions (telbivudine - tenofovir arm) and the 95% CI of the difference.95% CI: [-9.4, 3.1]
Comparison: Imputing LOCF DNA for wk 52: d/c for non response prior to Wk 52: Treating missing as failure for patients who discontinued prior to Week 52 due to unsatisfactory therapeutic effect and imputing missing with LOCF for other patients95% CI: [-7.9, 0.4]
Comparison: Imputing within +28d DNA for wk52: d/c for non response \<28 days from Wk 52:Treating missing as failure for patients who discontinued prior to Week 52 due to unsatisfactory therapeutic effect and imputing missing with the earliest available assessment within the 28-day window starting from the scheduled Week 52 date for other patients (if no such assessment is available, treated as failure)95% CI: [-8.3, 3.8]
Secondary
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
eGFR changes were calculated using the Modification of Diet in Renal Disease (MDRD) formula: GFR = 186 x (sCr)\^(-1.154) x (age)\^-0.203 with Female: Multiply GFR by 0.742; Black: Multiply GFR by 1.210. sCr is Serum Creatinine in mg/dl (measured at each scheduled visit). Age in years at visit (=\[sCr sample collection date -Date of birth\]/365.25). Weight in kilograms, as measured at the visit or the closest previous visit Safety population.
Time frame: Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeks
Population: Safety population consisted of patients who received at least 1 dose of study drug and had 1 post-baseline safety assessment. Numbers in parentheses represent the number of participants who met the criteria for the measurement in the 2 LDT arms, LDT Overall, 2 TDF arms, TDF Overall, respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Baseline actual(98,22,120,109,11,120) | 94.71 mL/min/1.73 m2 | Standard Deviation 16.422 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 actual(97,22,119,108,11,119) | 100.18 mL/min/1.73 m2 | Standard Deviation 20.257 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 change(97,22,119,108,11,119) | 5.18 mL/min/1.73 m2 | Standard Deviation 18.842 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 change(97,22,119,108,11,119) | 5.19 mL/min/1.73 m2 | Standard Deviation 16.583 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 change(62,17,79,79,10,89) | 8.07 mL/min/1.73 m2 | Standard Deviation 16.777 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 actual(97,22,119,108,11,119) | 96.43 mL/min/1.73 m2 | Standard Deviation 16.434 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 change (97,22,119,108,11,119) | 1.43 mL/min/1.73 m2 | Standard Deviation 12.815 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 actual(62,17,79,79,10,89) | 101.33 mL/min/1.73 m2 | Standard Deviation 18.505 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 actual (97,22,119,108,11,119) | 100.20 mL/min/1.73 m2 | Standard Deviation 16.287 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Baseline actual(98,22,120,109,11,120) | 109.79 mL/min/1.73 m2 | Standard Deviation 19.56 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 actual(97,22,119,108,11,119) | 102.99 mL/min/1.73 m2 | Standard Deviation 19.425 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 change(62,17,79,79,10,89) | -10.89 mL/min/1.73 m2 | Standard Deviation 14.993 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 change(97,22,119,108,11,119) | -6.80 mL/min/1.73 m2 | Standard Deviation 17.229 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 actual (97,22,119,108,11,119) | 104.02 mL/min/1.73 m2 | Standard Deviation 18.201 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 change(97,22,119,108,11,119) | -5.77 mL/min/1.73 m2 | Standard Deviation 15.943 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 actual(97,22,119,108,11,119) | 97.73 mL/min/1.73 m2 | Standard Deviation 17.69 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 actual(62,17,79,79,10,89) | 100.70 mL/min/1.73 m2 | Standard Deviation 20.029 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 change (97,22,119,108,11,119) | -12.06 mL/min/1.73 m2 | Standard Deviation 14.394 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 actual (97,22,119,108,11,119) | 100.90 mL/min/1.73 m2 | Standard Deviation 16.643 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Baseline actual(98,22,120,109,11,120) | 97.47 mL/min/1.73 m2 | Standard Deviation 17.936 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 change(97,22,119,108,11,119) | 3.16 mL/min/1.73 m2 | Standard Deviation 16.947 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 change (97,22,119,108,11,119) | -1.07 mL/min/1.73 m2 | Standard Deviation 14.076 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 change(97,22,119,108,11,119) | 2.96 mL/min/1.73 m2 | Standard Deviation 19.064 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 change(62,17,79,79,10,89) | 3.99 mL/min/1.73 m2 | Standard Deviation 18.104 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 actual(97,22,119,108,11,119) | 96.67 mL/min/1.73 m2 | Standard Deviation 16.603 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 actual(97,22,119,108,11,119) | 100.70 mL/min/1.73 m2 | Standard Deviation 20.054 |
| LdT Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 actual(62,17,79,79,10,89) | 101.20 mL/min/1.73 m2 | Standard Deviation 18.712 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 actual(97,22,119,108,11,119) | 93.32 mL/min/1.73 m2 | Standard Deviation 18.88 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 actual(97,22,119,108,11,119) | 93.61 mL/min/1.73 m2 | Standard Deviation 18.5 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 actual(62,17,79,79,10,89) | 88.83 mL/min/1.73 m2 | Standard Deviation 16.773 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 actual (97,22,119,108,11,119) | 92.19 mL/min/1.73 m2 | Standard Deviation 18.24 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 change(97,22,119,108,11,119) | -3.83 mL/min/1.73 m2 | Standard Deviation 15.157 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Baseline actual(98,22,120,109,11,120) | 95.91 mL/min/1.73 m2 | Standard Deviation 16.396 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 change(97,22,119,108,11,119) | -2.70 mL/min/1.73 m2 | Standard Deviation 18.636 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 change(62,17,79,79,10,89) | -5.34 mL/min/1.73 m2 | Standard Deviation 13.393 |
| TDF Mono at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 change (97,22,119,108,11,119) | -2.41 mL/min/1.73 m2 | Standard Deviation 14.885 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Baseline actual(98,22,120,109,11,120) | 94.50 mL/min/1.73 m2 | Standard Deviation 17.558 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 change(97,22,119,108,11,119) | -8.39 mL/min/1.73 m2 | Standard Deviation 10.479 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 change(97,22,119,108,11,119) | -8.69 mL/min/1.73 m2 | Standard Deviation 15.632 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 change (97,22,119,108,11,119) | -7.17 mL/min/1.73 m2 | Standard Deviation 15.368 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 change(62,17,79,79,10,89) | -6.67 mL/min/1.73 m2 | Standard Deviation 11.905 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 actual(97,22,119,108,11,119) | 87.33 mL/min/1.73 m2 | Standard Deviation 16.854 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 actual(97,22,119,108,11,119) | 86.12 mL/min/1.73 m2 | Standard Deviation 14.233 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 actual (97,22,119,108,11,119) | 85.81 mL/min/1.73 m2 | Standard Deviation 13.099 |
| TDF + LdT at Week 24 | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 actual(62,17,79,79,10,89) | 87.93 mL/min/1.73 m2 | Standard Deviation 13.28 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 actual(62,17,79,79,10,89) | 88.73 mL/min/1.73 m2 | Standard Deviation 16.355 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 actual (97,22,119,108,11,119) | 91.60 mL/min/1.73 m2 | Standard Deviation 17.879 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 156 change(62,17,79,79,10,89) | -5.49 mL/min/1.73 m2 | Standard Deviation 13.178 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 104 change(97,22,119,108,11,119) | -4.28 mL/min/1.73 m2 | Standard Deviation 15.2 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 change(97,22,119,108,11,119) | -3.22 mL/min/1.73 m2 | Standard Deviation 18.082 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 change (97,22,119,108,11,119) | -2.85 mL/min/1.73 m2 | Standard Deviation 14.928 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Baseline actual(98,22,120,109,11,120) | 95.78 mL/min/1.73 m2 | Standard Deviation 16.433 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 52 actual(97,22,119,108,11,119) | 92.66 mL/min/1.73 m2 | Standard Deviation 18.569 |
| TDF Overall | eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study | Week 24 actual(97,22,119,108,11,119) | 93.03 mL/min/1.73 m2 | Standard Deviation 18.378 |
Secondary
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA \<300 copies/mL (51 IU/mL) at Week156, ALT normalization, HBsAg loss, development of HBsAg conversion , cumulative tx emergent resistance, HBV DNA \<300 copies/mL with HBV DNA \<7 log at Baseline
Time frame: 156 weeks
Population: The modified ITT (mITT) population consisted of all patients in ITT population who were eligible and enrolled into the extension.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB Wk104-156 LOCF | 16.1 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx emerg resist Week 156 LOCF | 14.0 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB BL to Wk 156 LOCF | 21.0 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx-emerg resist Wk156 <7log LOCF | 8.7 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 LOCF | 88.7 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 | 14.3 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA <300 Wk156 <7 log LOCF | 88.2 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 LOCF | 85.7 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 <7 log at BL | 17.6 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBSAg loss/ seroconversion | 0 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Week 156 | 17.7 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx emerg resist Week 156 LOCF | 0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA <300 Wk156 <7 log LOCF | 100.0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 | 6.7 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBSAg loss/ seroconversion | 0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 LOCF | 93.3 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB Wk104-156 LOCF | 0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx-emerg resist Wk156 <7log LOCF | 0.0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB BL to Wk 156 LOCF | 0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 <7 log at BL | 0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Week 156 | 11.8 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 LOCF | 100.0 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB BL to Wk 156 LOCF | 16.5 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 LOCF | 91.1 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx-emerg resist Wk156 <7log LOCF | 8.2 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA <300 Wk156 <7 log LOCF | 88.9 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Week 156 | 16.5 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx emerg resist Week 156 LOCF | 10.8 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB Wk104-156 LOCF | 12.7 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 | 12.0 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 LOCF | 88.0 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 <7 log at BL | 16.7 percentage of participants |
| LdT Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBSAg loss/ seroconversion | 0 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA <300 Wk156 <7 log LOCF | 100.0 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 | 10.5 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB Wk104-156 LOCF | 1.3 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Week 156 | 13.9 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 LOCF | 100.0 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 LOCF | 86.8 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBSAg loss/ seroconversion | 0 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB BL to Wk 156 LOCF | 1.3 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx emerg resist Week 156 LOCF | 0 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 <7 log at BL | 11.7 percentage of participants |
| TDF Mono at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx-emerg resist Wk156 <7log LOCF | 0.0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 LOCF | 85.7 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 LOCF | 100.0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBSAg loss/ seroconversion | 0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA <300 Wk156 <7 log LOCF | 100.0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx-emerg resist Wk156 <7log LOCF | 0.0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Week 156 | 20.0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 <7 log at BL | 50.0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB Wk104-156 LOCF | 0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB BL to Wk 156 LOCF | 0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx emerg resist Week 156 LOCF | 0 percentage of participants |
| TDF + LdT at Week 24 | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 | 28.6 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB Wk104-156 LOCF | 1.1 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx-emerg resist Wk156 <7log LOCF | 0.0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum tx emerg resist Week 156 LOCF | 0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 LOCF | 86.7 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | ALT normalization Wk 156 | 13.3 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 <7 log at BL | 12.9 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Wk156 LOCF | 100.00 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA < 300 Week 156 | 14.6 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBV DNA <300 Wk156 <7 log LOCF | 100.0 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | Cum VB BL to Wk 156 LOCF | 1.1 percentage of participants |
| TDF Overall | Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) | HBSAg loss/ seroconversion | 0 percentage of participants |
Secondary
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA \<300 copies/mL (51 IU/mL), ALT normalization, HBsAg loss, HBsAg conversion, virologic breakthrough (VB) at study visit, cumulative VB by study defined study period, cumulative treatment-emergent resistance
Time frame: week 24, 52, 104
Population: Roadmap intent-to-treat (rITT) population was analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 104 | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 52 | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 104 LOCF | 92.0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 LOCF | 88.0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Week 104 | 70.0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk104 | 68.4 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk 104 LOCF | 9.2 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk52 LOCF | 3.3 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 104 | 69.6 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 | 98.9 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Ccum tx emergent resistance Wk 104 | 9.2 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resistance Wk 52 | 3.3 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BLto Wk 104 LOCF | 14.1 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk52-Wk104 LOCF | 12.0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 LOCF | 100.0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 104 LOCF | 92.1 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 LOCF | 3.3 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum vir break BL to Wk24 LOCF | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseLto Wk 104 | 14.1 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 52 to Wk 104 | 12.0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Wk104 LOCF | 92.4 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log at BL HBV DNA <300 Wk52 | 93.4 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 | 3.3 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseL to Wk 24 | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 104 | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 52 | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 | 84.0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 52 LOCF | 97.4 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Wk104 LOCF | 100.0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 | 0.0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 104 | 76.2 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 | 83.3 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Week 104 | 72.2 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 LOCF | 83.3 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 104 LOCF | 83.3 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 104 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 104 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseL to Wk 24 | 4.8 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 52 to Wk 104 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseLto Wk 104 | 4.8 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum vir break BL to Wk24 LOCF | 4.8 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk52-Wk104 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BLto Wk 104 LOCF | 4.8 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resistance Wk 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Ccum tx emergent resistance Wk 104 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk52 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk 104 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log at BL HBV DNA <300 Wk52 | 75.0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk104 | 50.0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 52 LOCF | 100.0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 104 LOCF | 100.0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk52-Wk104 LOCF | 9.7 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 52 LOCF | 97.5 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 LOCF | 2.7 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 104 | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 52 to Wk 104 | 9.7 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Week 104 | 70.6 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 LOCF | 81.4 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum vir break BL to Wk24 LOCF | 0.9 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 | 80.5 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 | 83.8 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseLto Wk 104 | 12.4 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk 104 LOCF | 7.4 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk52 LOCF | 2.7 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 52 | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 104 | 0 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 104 LOCF | 89.7 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Ccum tx emergent resistance Wk 104 | 7.4 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 104 | 70.8 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log at BL HBV DNA <300 Wk52 | 92.5 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 LOCF | 86.8 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseL to Wk 24 | 0.9 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 104 LOCF | 92.5 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resistance Wk 52 | 2.7 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BLto Wk 104 LOCF | 12.4 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Wk104 LOCF | 93.8 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk104 | 67.5 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 | 2.7 percentage of particiipants |
| LdT Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 52 | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 LOCF | 100.0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 104 | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 52 | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 | 99.1 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 104 | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Wk104 LOCF | 99.1 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 104 LOCF | 98.8 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseL to Wk 24 | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk104 | 76.3 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 52 to Wk 104 | 1.9 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseLto Wk 104 | 1.9 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum vir break BL to Wk24 LOCF | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 LOCF | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk52-Wk104 LOCF | 1.9 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 52 LOCF | 100.0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BLto Wk 104 LOCF | 1.9 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 104 | 74.5 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resistance Wk 52 | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Ccum tx emergent resistance Wk 104 | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk52 LOCF | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk 104 LOCF | 0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Week 104 | 61.4 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 LOCF | 87.7 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 104 LOCF | 86.0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 | 82.5 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log at BL HBV DNA <300 Wk52 | 95.0 percentage of particiipants |
| TDF Mono at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 52 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 104 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resistance Wk 52 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 LOCF | 85.7 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk 104 LOCF | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 | 85.7 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 52 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BLto Wk 104 LOCF | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Week 104 | 85.7 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 104 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log at BL HBV DNA <300 Wk52 | 100.0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Ccum tx emergent resistance Wk 104 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseLto Wk 104 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 104 | 81.8 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk104 | 66.7 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 LOCF | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk52-Wk104 LOCF | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 52 LOCF | 100.0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum vir break BL to Wk24 LOCF | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Wk104 LOCF | 100.0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 52 to Wk 104 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 104 LOCF | 100.0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 104 LOCF | 85.7 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 52 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 LOCF | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk52 LOCF | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseL to Wk 24 | 0 percentage of particiipants |
| TDF + LdT at Week 24 | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk52-Wk104 LOCF | 1.7 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 LOCF | 87.5 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseL to Wk 24 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BLto Wk 104 LOCF | 1.7 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 104 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resistance Wk 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 104 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 52 LOCF | 100.0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Ccum tx emergent resistance Wk 104 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 | 89.7 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk104 | 75.9 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk52 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log HBV DNA <300 Wk 104 LOCF | 98.8 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg conversion Week 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 104 LOCF | 85.9 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum tx emergent resist Wk 104 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBsAg loss Week 52 | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Week 104 | 64.1 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | ALT Normalization Wk 52 | 82.8 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | <7 log at BL HBV DNA <300 Wk52 | 95.2 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break BaseLto Wk 104 | 1.7 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 52 to Wk 104 | 1.7 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Wk104 LOCF | 99.1 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum vir break BL to Wk24 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 24 LOCF | 90.6 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | Cum virol break Wk 24 to Wk 52 LOCF | 0 percentage of particiipants |
| TDF Overall | Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) | HBV DNA <300 Week 104 | 75.2 percentage of particiipants |