Chronic Hepatitis B
Conditions
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching to tenofovir alafenamide (TAF) versus continuing tenofovir disoproxil fumarate (TDF) in virologically suppressed adults with chronic hepatitis B virus (HBV) infection.
Interventions
DRUGTAF
25 mg tablet administered orally once daily
DRUGTDF
300 mg tablet administered orally once daily
DRUGTAF Placebo
Tablet administered orally once daily
DRUGTDF Placebo
Tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures * Adult male and non-pregnant, non-lactating females * Documented evidence of chronic hepatitis B virus (HBV) infection previously * Maintained on tenofovir disoproxil fumarate (TDF) 300 mg once daily for at least 48 weeks, and as monotherapy for chronic hepatitis B for at least 24 weeks with viral suppression (HBV DNA \< lower limit of quantitation) for a minimum of 12 weeks prior to screening * Adequate renal function * Normal Electrocardiogram Key
Exclusion criteria
* Pregnant women or women who are breastfeeding * Males and females of reproductive potential who are unwilling to use an effective, protocol-specified method(s) of contraception during the study. * Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or human immunodeficiency virus (HIV) * Evidence of hepatocellular carcinoma * Current evidence of, or recent (≤ 5 year) history of clinical hepatic decompensation * Abnormal hematological and biochemical parameters, including: * Hemoglobin \< 10 g/dL * Absolute neutrophil count \< 750/mm\^3 * Platelets ≤ 50,000/mm\^3 * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 × upper limit of the normal (ULN) * Albumin \< 3.0 mg/ dL * International normalized ratio (INR) \> 1.5 × ULN (unless stable on anticoagulant regimen) * Total bilirubin \> 2.5 × ULN * Received solid organ or bone marrow transplant * Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (eg, basal cell skin cancer). Individuals under evaluation for possible malignancy are not eligible. * Currently receiving therapy with immunomodulators (eg, corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion * Individuals receiving ongoing therapy with drugs not to be used with TAF or TDF or individuals with a known hypersensitivity to study drugs, metabolites, or formulation excipients * Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance * Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements. * Use of investigational agents within 3 months of screening, unless allowed by the sponsor Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | Week 48 | The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and * Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48 | Weeks 48 | The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 48 analysis window. Missing=Failure (M = F) approach was used for analysis. |
| Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | Week 48 | The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 48 analysis window. The method of determining percentage of participants with HBV DNA levels \<20 IU/mL (target detected/not detected i.e., lower limit of detection) at Week 48, was handled by M = F, and Missing=Excluded (M = E) approaches. |
| Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96 | Week 96 | The percentage of participants with HBV DNA \< 20 IU/mL at Week 96 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 96 analysis window. M = F approach was used for analysis. |
| Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | Week 96 | The percentage of participants with HBV DNA \< 20 IU/mL at Week 96 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 96 analysis window. The method of determining percentage of participants with HBV DNA levels \<20 IU/mL (target detected/not detected i.e., lower limit of detection) at Week 96, was handled by Missing=Failure (M = F), and Missing=Excluded (M = E) approaches. |
| Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48 | Week 48 | HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline visit with baseline HBeAb negative or missing. The M = F approach was used for this analysis. |
| Percentage of Participants With HBeAg Seroconversion at Week 48 | Week 48 | HBeAg seroconversion was defined as HBeAg loss and HBeAb changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With HBeAg Loss at Week 96 | Week 96 | HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline visit with baseline HBeAb negative or missing. The M = F approach was used for this analysis. |
| Percentage of Participants With HBeAg Seroconversion at Week 96 | Week 96 | HBeAg seroconversion was defined as HBeAg loss and HBeAb changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 | Week 48 | HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline visit with baseline HBsAb negative or missing. The M = F approach was used for this analysis. |
| Percentage of Participants With HBsAg Seroconversion at Week 48 | Week 48 | HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With HBsAg Loss at Week 96 | Week 96 | HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline visit with baseline HBsAb negative or missing. The M = F approach was used for this analysis. |
| Percentage of Participants With HBsAg Seroconversion at Week 96 | Week 96 | HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm | Week 96 | The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 96 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 96 analysis window (from Day 589 to Day 840, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 96 analysis window and * Discontinued study drug prior to or in the Week 96 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 96 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL |
| Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria) | Week 48 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis. |
| Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria) | Week 96 | Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis. |
| Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria) | Week 96 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis. |
| Change From Baseline in FibroTest® Score at Week 48 | Baseline; Week 48 | The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 48 minus the value at Baseline. |
| Change From Baseline in FibroTest® Score at Week 96 | Baseline; Week 96 | The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 96 minus the value at Baseline. |
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | Baseline; Week 48 | Percent Change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percent Change From Baseline in Hip BMD at Week 96 | Baseline; Week 96 | Percent Change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percent Change From Baseline in Spine BMD at Week 48 | Baseline; Week 48 | Percent Change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percent Change From Baseline in Spine BMD at Week 96 | Baseline; Week 96 | Percent Change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48 | Baseline; Week 48 | Cockcroft-Gault formula is as follows: * For men: Glomerular filtration rate (GFR) = (140 - age in years) \* body weight in kg / 72 \* serum creatinine (mg/dL) * For women: GFR = 0.85 \* (140 - age in years) \* body weight in kg / 72 \* serum creatinine (mg/dL). Change from baseline was calculated as the value at Week 48 minus the value at Baseline. |
| Change From Baseline in eGFR-CG at Week 96 | Baseline; Week 96 | Cockcroft-Gault formula is as follows: * For men: Glomerular filtration rate (GFR) = (140 - age in years) \* body weight in kg / 72 \* serum creatinine (mg/dL) * For women: GFR = 0.85 \* (140 - age in years) \* body weight in kg / 72 \* serum creatinine (mg/dL). Change from baseline was calculated as the value at Week 96 minus the value at Baseline. |
| Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria) | Week 48 | Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis. |
Countries
Canada, Hong Kong, Italy, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Europe, and Asia. The first participant was screened on 29 December 2016. The last study visit occurred on 30 January 2020.
Pre-assignment details
541 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| TAF 25 mg Participants who were virologically suppressed and taking TDF 300 mg tablet orally once daily received TAF 25 mg tablet orally once daily, and placebo to match TDF once daily for up to 53 weeks in the DB phase. Participants who completed DB treatment and were willing to enter in the OLE phase, received TAF 25 mg tablet orally once daily for up to 52 weeks. | 243 |
| TDF 300 mg Participants who were virologically suppressed and taking TDF 300 mg tablet orally once daily received TDF 300 mg tablet orally once daily, and placebo to match TAF once daily for up to 50 weeks in the DB phase. Participants who completed DB treatment and were willing to enter in the OLE phase, received TAF 25 mg tablet orally once daily for up to 52 weeks. | 245 |
| Total | 488 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Phase | Adverse Event | 2 | 0 |
| Double-Blind Phase | Lost to Follow-up | 1 | 1 |
| Double-Blind Phase | Pregnancy | 2 | 2 |
| Double-Blind Phase | Protocol Violation | 1 | 1 |
| Double-Blind Phase | Randomized but Never Treated | 2 | 0 |
| Double-Blind Phase | Withdrew Consent | 2 | 4 |
| Open-Label Extension (OLE) Phase | Adverse Event | 1 | 0 |
| Open-Label Extension (OLE) Phase | Death | 0 | 1 |
| Open-Label Extension (OLE) Phase | Investigator's Discretion | 0 | 1 |
| Open-Label Extension (OLE) Phase | Withdrew Consent | 2 | 4 |
Baseline characteristics
| Characteristic | Total | TAF 25 mg | TDF 300 mg |
|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 10.7 | 51 years STANDARD_DEVIATION 10.5 | 51 years STANDARD_DEVIATION 10.8 |
| Age, Customized < 50 Years | 216 Participants | 107 Participants | 109 Participants |
| Age, Customized ≥ 50 Years | 272 Participants | 136 Participants | 136 Participants |
| Alanine Aminotransferase (ALT) | 27 U/L STANDARD_DEVIATION 13.9 | 28 U/L STANDARD_DEVIATION 15.6 | 26 U/L STANDARD_DEVIATION 12 |
| ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range > 5xULN | 0 Participants | 0 Participants | 0 Participants |
| ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range ≤ ULN | 383 Participants | 191 Participants | 192 Participants |
| ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range > ULN to 5xULN | 105 Participants | 52 Participants | 53 Participants |
| ALT Level Based on Central Lab Normal Range > 5xULN | 0 Participants | 0 Participants | 0 Participants |
| ALT Level Based on Central Lab Normal Range ≤ ULN | 437 Participants | 211 Participants | 226 Participants |
| ALT Level Based on Central Lab Normal Range > ULN to 5xULN | 51 Participants | 32 Participants | 19 Participants |
| Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) | 94.4 mL/min STANDARD_DEVIATION 25.35 | 95.0 mL/min STANDARD_DEVIATION 25.58 | 93.8 mL/min STANDARD_DEVIATION 25.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 485 Participants | 240 Participants | 245 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| FibroTest® Score | 0.42 scores on a scale STANDARD_DEVIATION 0.223 | 0.42 scores on a scale STANDARD_DEVIATION 0.234 | 0.41 scores on a scale STANDARD_DEVIATION 0.211 |
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Negative/Negative | 45 Participants | 17 Participants | 28 Participants |
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Negative/Positive | 286 Participants | 148 Participants | 138 Participants |
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Positive/Negative | 156 Participants | 78 Participants | 78 Participants |
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Positive/Positive | 1 Participants | 0 Participants | 1 Participants |
| Hepatitis B virus (HBV) DNA Category < 20 IU/mL | 480 Participants | 238 Participants | 242 Participants |
| Hepatitis B virus (HBV) DNA Category 20 to < 69 IU/mL | 5 Participants | 2 Participants | 3 Participants |
| Hepatitis B virus (HBV) DNA Category ≥ 69 IU/mL | 3 Participants | 3 Participants | 0 Participants |
| Hip Bone Mineral Density (BMD) Status Normal (T-score ≥ -1.0) | 267 Participants | 143 Participants | 124 Participants |
| Hip Bone Mineral Density (BMD) Status Osteopenia (-2.5 ≤ T-score < -1.0) | 205 Participants | 89 Participants | 116 Participants |
| Hip Bone Mineral Density (BMD) Status Osteoporosis (T-score < -2.5) | 13 Participants | 9 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Asian | 400 Participants | 195 Participants | 205 Participants |
| Race/Ethnicity, Customized Race Black or African American | 17 Participants | 9 Participants | 8 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 69 Participants | 38 Participants | 31 Participants |
| Region of Enrollment Canada | 89 Participants | 42 Participants | 47 Participants |
| Region of Enrollment Hong Kong | 28 Participants | 15 Participants | 13 Participants |
| Region of Enrollment Italy | 21 Participants | 9 Participants | 12 Participants |
| Region of Enrollment South Korea | 138 Participants | 61 Participants | 77 Participants |
| Region of Enrollment Spain | 31 Participants | 19 Participants | 12 Participants |
| Region of Enrollment Taiwan | 41 Participants | 28 Participants | 13 Participants |
| Region of Enrollment United Kingdom | 13 Participants | 6 Participants | 7 Participants |
| Region of Enrollment United States | 127 Participants | 63 Participants | 64 Participants |
| Sex: Female, Male Female | 143 Participants | 64 Participants | 79 Participants |
| Sex: Female, Male Male | 345 Participants | 179 Participants | 166 Participants |
| Spine BMD Status Normal (T-score ≥ -1.0) | 245 Participants | 125 Participants | 120 Participants |
| Spine BMD Status Osteopenia (-2.5 ≤ T-score < -1.0) | 187 Participants | 90 Participants | 97 Participants |
| Spine BMD Status Osteoporosis (T-score < -2.5) | 56 Participants | 28 Participants | 28 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 | 0 / 243 | 0 / 245 | 0 / 235 | 1 / 237 |
| other Total, other adverse events | 31 / 243 | 28 / 245 | 15 / 235 | 15 / 237 |
| serious Total, serious adverse events | 11 / 243 | 3 / 245 | 8 / 235 | 5 / 237 |
Outcome results
Primary
Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and * Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
Time frame: Week 48
Population: The Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 0.4 percentage of participants |
| TDF 300 mg | Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 0.4 percentage of participants |
Comparison: The null hypothesis was that the TAF group is at least 4% worse than the TDF group with respect to the percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48. The alternative hypothesis was that the TAF group is less than 4% worse than the TDF group with respect to the percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48.95% CI: [-1.9, 2]
Secondary
Change From Baseline in eGFR-CG at Week 96
Cockcroft-Gault formula is as follows: * For men: Glomerular filtration rate (GFR) = (140 - age in years) \* body weight in kg / 72 \* serum creatinine (mg/dL) * For women: GFR = 0.85 \* (140 - age in years) \* body weight in kg / 72 \* serum creatinine (mg/dL). Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Time frame: Baseline; Week 96
Population: Participants in the Safety Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAF 25 mg | Change From Baseline in eGFR-CG at Week 96 | 1.626 mL/min |
| TDF 300 mg | Change From Baseline in eGFR-CG at Week 96 | 0.544 mL/min |
p-value: 0.7535Wilcoxon rank sum test
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48
Cockcroft-Gault formula is as follows: * For men: Glomerular filtration rate (GFR) = (140 - age in years) \* body weight in kg / 72 \* serum creatinine (mg/dL) * For women: GFR = 0.85 \* (140 - age in years) \* body weight in kg / 72 \* serum creatinine (mg/dL). Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Time frame: Baseline; Week 48
Population: Participants in the Safety Analysis Set (included all randomized participants who received at least 1 dose of study drug) with available data were analyzed. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAF 25 mg | Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48 | 2.240 mL/min |
| TDF 300 mg | Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48 | -1.722 mL/min |
p-value: <0.0001Wilcoxon rank sum test
Secondary
Change From Baseline in FibroTest® Score at Week 48
The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Time frame: Baseline; Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAF 25 mg | Change From Baseline in FibroTest® Score at Week 48 | -0.02 scores on a scale | Standard Deviation 0.082 |
| TDF 300 mg | Change From Baseline in FibroTest® Score at Week 48 | -0.01 scores on a scale | Standard Deviation 0.082 |
Comparison: P-value, difference in least squares mean (LSM), and its 95% CI were derived from analysis of variance (ANOVA) model with baseline age groups (\< 50, ≥ 50 years), baseline HBeAg status, and treatment group as fixed effects in the model.p-value: 0.018695% CI: [-0.03, 0]ANOVA
Secondary
Change From Baseline in FibroTest® Score at Week 96
The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Time frame: Baseline; Week 96
Population: Participants in the Full Analysis Set with available data were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAF 25 mg | Change From Baseline in FibroTest® Score at Week 96 | -0.03 scores on a scale | Standard Deviation 0.08 |
| TDF 300 mg | Change From Baseline in FibroTest® Score at Week 96 | -0.03 scores on a scale | Standard Deviation 0.09 |
Comparison: P-value, difference in LSM, and its 95% CI were from ANOVA with baseline age groups (\<50, ≥ 50 years), baseline HBeAg status, and treatment group as fixed effects in the model.p-value: 0.695695% CI: [-0.02, 0.01]ANOVA
Secondary
Percentage of Participants With HBeAg Loss at Week 96
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline visit with baseline HBeAb negative or missing. The M = F approach was used for this analysis.
Time frame: Week 96
Population: Participants in the Serologically Evaluable Full Analysis Set for HBeAg loss and seroconversion were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBeAg Loss at Week 96 | 17.9 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBeAg Loss at Week 96 | 9.0 percentage of participants |
p-value: 0.100595% CI: [-2, 20.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HBeAg Seroconversion at Week 48
HBeAg seroconversion was defined as HBeAg loss and HBeAb changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 48
Population: Participants in the Serologically Evaluable Full Analysis Set for HBeAg loss and seroconversion were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBeAg Seroconversion at Week 48 | 2.6 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBeAg Seroconversion at Week 48 | 0.0 percentage of participants |
p-value: 0.134895% CI: [-2.3, 7.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HBeAg Seroconversion at Week 96
HBeAg seroconversion was defined as HBeAg loss and HBeAb changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 96
Population: Participants in the Serologically Evaluable Full Analysis Set for HBeAg loss and seroconversion were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBeAg Seroconversion at Week 96 | 5.1 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBeAg Seroconversion at Week 96 | 2.6 percentage of participants |
p-value: 0.415495% CI: [-4.5, 9.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HBsAg Loss at Week 96
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline visit with baseline HBsAb negative or missing. The M = F approach was used for this analysis.
Time frame: Week 96
Population: Participants in the Serologically Evaluable Full Analysis Set for HBsAg loss and seroconversion were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBsAg Loss at Week 96 | 1.6 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBsAg Loss at Week 96 | 2.4 percentage of participants |
p-value: 0.537395% CI: [-3.7, 2.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HBsAg Seroconversion at Week 48
HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 48
Population: Participants in the Serologically Evaluable Full Analysis Set for HBsAg loss and seroconversion were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBsAg Seroconversion at Week 48 | 0.0 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBsAg Seroconversion at Week 48 | 0.0 percentage of participants |
Secondary
Percentage of Participants With HBsAg Seroconversion at Week 96
HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 96
Population: Participants in the Serologically Evaluable Full Analysis Set for HBsAg loss and seroconversion were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBsAg Seroconversion at Week 96 | 0.8 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBsAg Seroconversion at Week 96 | 0.4 percentage of participants |
p-value: 0.584595% CI: [-1.7, 2.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48
The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 48 analysis window. Missing=Failure (M = F) approach was used for analysis.
Time frame: Weeks 48
Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48 | 96.3 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48 | 96.3 percentage of participants |
95% CI: [-3.7, 3.7]
p-value: 0.98Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96
The percentage of participants with HBV DNA \< 20 IU/mL at Week 96 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 96 analysis window. M = F approach was used for analysis.
Time frame: Week 96
Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96 | 94.7 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96 | 93.9 percentage of participants |
95% CI: [-3.5, 5.2]
p-value: 0.6863Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm
The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 96 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 96 analysis window (from Day 589 to Day 840, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 96 analysis window and * Discontinued study drug prior to or in the Week 96 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 96 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
Time frame: Week 96
Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm | 0.4 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm | 0.4 percentage of participants |
95% CI: [-1.9, 1.9]
p-value: 0.9953Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48
The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 48 analysis window. The method of determining percentage of participants with HBV DNA levels \<20 IU/mL (target detected/not detected i.e., lower limit of detection) at Week 48, was handled by M = F, and Missing=Excluded (M = E) approaches.
Time frame: Week 48
Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | M = F Approach: < 20 IU/mL Target Not Detected | 63.4 percentage of participants |
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | M = F Approach: < 20 IU/mL Target Detected | 32.9 percentage of participants |
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | M = E Approach: < 20 IU/mL Target Not Detected | 65.5 percentage of participants |
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | M = E Approach: < 20 IU/mL Target Detected | 34.0 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | M = E Approach: < 20 IU/mL Target Detected | 35.4 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | M = F Approach: < 20 IU/mL Target Not Detected | 62.0 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | M = E Approach: < 20 IU/mL Target Not Detected | 64.1 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 | M = F Approach: < 20 IU/mL Target Detected | 34.3 percentage of participants |
Secondary
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96
The percentage of participants with HBV DNA \< 20 IU/mL at Week 96 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 96 analysis window. The method of determining percentage of participants with HBV DNA levels \<20 IU/mL (target detected/not detected i.e., lower limit of detection) at Week 96, was handled by Missing=Failure (M = F), and Missing=Excluded (M = E) approaches.
Time frame: Week 96
Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | M = F Approach: < 20 IU/mL Target Not Detected | 65.8 percentage of participants |
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | M = F Approach: < 20 IU/mL Target Detected | 28.8 percentage of participants |
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | M = E Approach: < 20 IU/mL Target Not Detected | 69.3 percentage of participants |
| TAF 25 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | M = E Approach: < 20 IU/mL Target Detected | 30.3 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | M = E Approach: < 20 IU/mL Target Detected | 29.4 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | M = F Approach: < 20 IU/mL Target Not Detected | 66.1 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | M = E Approach: < 20 IU/mL Target Not Detected | 70.1 percentage of participants |
| TDF 300 mg | Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 | M = F Approach: < 20 IU/mL Target Detected | 27.8 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline visit with baseline HBeAb negative or missing. The M = F approach was used for this analysis.
Time frame: Week 48
Population: The Serologically Evaluable Full Analysis Set for HBeAg loss and seroconversion included all participants who were randomized and received at least 1 dose of study drug and were HBeAg-positive and HBeAb-negative or had a missing value at baseline. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48 | 7.7 percentage of participants |
| TDF 300 mg | Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48 | 6.4 percentage of participants |
p-value: 0.725895% CI: [-7.2, 10.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline visit with baseline HBsAb negative or missing. The M = F approach was used for this analysis.
Time frame: Week 48
Population: The Serologically Evaluable Full Analysis Set for HBsAg loss and seroconversion included all participants who were randomized and received at least 1 dose of study drug and were HBsAg-positive and HBsAb-negative or had a missing value at baseline. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAF 25 mg | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 | 0.0 percentage of participants |
| TDF 300 mg | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 | 2.0 percentage of participants |
p-value: 0.028195% CI: [-4.4, 0.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria)
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Time frame: Week 48
Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAF 25 mg | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria) | Central Laboratory Criteria | 89.3 percentage of participants |
| TAF 25 mg | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria) | AASLD Criteria | 79.0 percentage of participants |
| TDF 300 mg | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria) | Central Laboratory Criteria | 84.9 percentage of participants |
| TDF 300 mg | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria) | AASLD Criteria | 75.1 percentage of participants |
Comparison: Central Laboratory Criteriap-value: 0.140595% CI: [-1.6, 10.6]Cochran-Mantel-Haenszel
Comparison: AASLD Criteriap-value: 0.313395% CI: [-3.7, 11.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria)
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Time frame: Week 96
Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAF 25 mg | Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria) | Central Laboratory Criteria | 88.5 percentage of participants |
| TAF 25 mg | Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria) | AASLD Criteria | 80.7 percentage of participants |
| TDF 300 mg | Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria) | Central Laboratory Criteria | 91.4 percentage of participants |
| TDF 300 mg | Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria) | AASLD Criteria | 86.5 percentage of participants |
Comparison: Central Laboratory Criteriap-value: 0.280395% CI: [-8.4, 2.6]Cochran-Mantel-Haenszel
Comparison: AASLD Criteriap-value: 0.078895% CI: [-12.6, 0.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria)
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Time frame: Week 48
Population: Participants in the Full Analysis Set with Baseline ALT \> ULN were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAF 25 mg | Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria) | Central Laboratory Criteria | 50.0 percentage of participants |
| TAF 25 mg | Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria) | AASLD Criteria | 50.0 percentage of participants |
| TDF 300 mg | Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria) | Central Laboratory Criteria | 36.8 percentage of participants |
| TDF 300 mg | Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria) | AASLD Criteria | 26.4 percentage of participants |
Comparison: Central Laboratory criteriap-value: 0.338195% CI: [-16.4, 44.6]Cochran-Mantel-Haenszel
Comparison: AASLD Criteriap-value: 0.013695% CI: [5.3, 42.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria)
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Time frame: Week 96
Population: Participants in the Full Analysis Set with Baseline ALT \> ULN were analyzed. Participants were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAF 25 mg | Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria) | Central Laboratory Criteria | 56.3 percentage of participants |
| TAF 25 mg | Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria) | AASLD Criteria | 55.8 percentage of participants |
| TDF 300 mg | Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria) | Central Laboratory Criteria | 78.9 percentage of participants |
| TDF 300 mg | Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria) | AASLD Criteria | 73.6 percentage of participants |
Comparison: Central Laboratory Criteriap-value: 0.08895% CI: [-51.2, 3.4]Cochran-Mantel-Haenszel
Comparison: AASLD Criteriap-value: 0.05195% CI: [-37.4, 0.2]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Hip BMD at Week 96
Percent Change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline; Week 96
Population: Participants in the Hip DXA Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAF 25 mg | Percent Change From Baseline in Hip BMD at Week 96 | 1.157 percent change | Standard Deviation 2.8501 |
| TDF 300 mg | Percent Change From Baseline in Hip BMD at Week 96 | 0.180 percent change | Standard Deviation 2.6813 |
Comparison: P-value, difference in LSM, and its 95% CI were from ANOVA with baseline age groups (\<50, ≥ 50 years), baseline HBeAg status, and treatment group as fixed effects in the model.p-value: 0.000295% CI: [0.465, 1.49]ANOVA
Secondary
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Percent Change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline; Week 48
Population: Participants in the Hip DXA Analysis Set (included all participants who were randomized into the study, received at least 1 dose of study drug, and had non-missing baseline hip BMD values) with available data were analysed. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAF 25 mg | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | 0.659 percent change | Standard Deviation 2.0818 |
| TDF 300 mg | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | -0.507 percent change | Standard Deviation 1.9051 |
Comparison: P-value, difference in LSM, and its 95% CI were from ANOVA with baseline age groups (\<50, ≥ 50 years), baseline HBeAg status, and treatment group as fixed effects in the model.p-value: <0.000195% CI: [0.797, 1.536]ANOVA
Secondary
Percent Change From Baseline in Spine BMD at Week 48
Percent Change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline; Week 48
Population: Participants in the Spine DXA Analysis Set (included all participants who were randomized into the study, received at least 1 dose of study drug, and had non-missing baseline spine BMD values) with available data were analysed. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAF 25 mg | Percent Change From Baseline in Spine BMD at Week 48 | 1.743 percent change | Standard Deviation 3.4674 |
| TDF 300 mg | Percent Change From Baseline in Spine BMD at Week 48 | -0.138 percent change | Standard Deviation 3.1072 |
Comparison: P-value, difference in LSM, and its 95% CI were from ANOVA with baseline age groups (\<50, ≥ 50 years), baseline HBeAg status, and treatment group as fixed effects in the model.p-value: <0.000195% CI: [1.275, 2.486]ANOVA
Secondary
Percent Change From Baseline in Spine BMD at Week 96
Percent Change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline; Week 96
Population: Participants in the Spine DXA Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAF 25 mg | Percent Change From Baseline in Spine BMD at Week 96 | 2.330 percent change | Standard Deviation 3.9301 |
| TDF 300 mg | Percent Change From Baseline in Spine BMD at Week 96 | 1.726 percent change | Standard Deviation 3.8224 |
Comparison: P-value, difference in LSM, and its 95% CI were from ANOVA with baseline age groups (\<50, ≥ 50 years), baseline HBeAg status, and treatment group as fixed effects in the model.p-value: 0.09795% CI: [-0.11, 1.317]ANOVA