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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
490
25 mg tablet administered orally once daily
300 mg tablet administered orally once daily
Tablet administered orally once daily
Unnamed facility
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
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
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
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48
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Tablet administered orally once daily
Los Angeles, California, United States
Unnamed facility
Palo Alto, California, United States
Unnamed facility
Pasadena, California, United States
Unnamed facility
San Diego, California, United States
Unnamed facility
San Francisco, California, United States
Unnamed facility
San Jose, California, United States
Unnamed facility
Baltimore, Maryland, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
Novi, Michigan, United States
Unnamed facility
Flushing, New York, United States
...and 29 more locations
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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