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Study to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02979613
Collaborator
(none)
490
Enrollment
39
Locations
2
Arms
37
Actual Duration (Months)
12.6
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
490 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Switching From Tenofovir Disoproxil Fumarate (TDF) 300 mg QD to Tenofovir Alafenamide (TAF) 25 mg QD in Subjects With Chronic Hepatitis B Who Are Virologically Suppressed
Actual Study Start Date :
Dec 29, 2016
Actual Primary Completion Date :
Sep 10, 2018
Actual Study Completion Date :
Jan 30, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: TAF 25 mg

Double-blind (DB) phase: TAF 25 mg + TDF placebo for up to 53 weeks. Open-label extension (OLE) phase: TAF 25 mg for up to 52 weeks.

Drug: TAF
25 mg tablet administered orally once daily
Other Names:
  • Vemlidy®
  • GS-7340

    • Drug: TDF Placebo
    Tablet administered orally once daily
    Active Comparator: TDF 300 mg

    DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.

    Drug: TAF
    25 mg tablet administered orally once daily
    Other Names:
  • Vemlidy®
  • GS-7340

    • Drug: TDF
    300 mg tablet administered orally once daily
    Other Names:
  • Viread®

    • Drug: TAF Placebo
    Tablet administered orally once daily

    Outcome Measures

    Primary Outcome Measures

    1. 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: 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 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 Outcome Measures

    1. 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: 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 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

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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.

    20. 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%.

    21. Percent Change From Baseline in Hip BMD at Week 96 [Baseline; Week 96]

      Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.

    22. Percent Change From Baseline in Spine BMD at Week 48 [Baseline; Week 48]

      Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.

    23. Percent Change From Baseline in Spine BMD at Week 96 [Baseline; Week 96]

      Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.

    24. 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.

    25. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Los Angeles California United States
    2 Palo Alto California United States
    3 Pasadena California United States
    4 San Diego California United States
    5 San Francisco California United States
    6 San Jose California United States
    7 Baltimore Maryland United States
    8 Boston Massachusetts United States
    9 Novi Michigan United States
    10 Flushing New York United States 11355
    11 Flushing New York United States
    12 New York New York United States 10029
    13 New York New York United States
    14 Philadelphia Pennsylvania United States 19107
    15 Philadelphia Pennsylvania United States
    16 Nashville Tennessee United States
    17 Sugar Land Texas United States 77478
    18 Edmonton Canada
    19 Toronto Canada
    20 Vancouver Canada
    21 Hong Kong Hong Kong
    22 Kowloon Hong Kong
    23 Milan Italy 20122
    24 Goyang Gyeonggi-d Korea, Republic of
    25 Daegu Korea, Republic of 700-721
    26 Seoul Korea, Republic of 03722
    27 Seoul Korea, Republic of 03830
    28 Seoul Korea, Republic of 05505
    29 Seoul Korea, Republic of 06973
    30 Seoul Korea, Republic of 135-710
    31 Seoul Korea, Republic of 152-703
    32 Seoul Korea, Republic of
    33 Barcelona Spain
    34 Majadahonda Spain
    35 Chiayi City Taiwan 60002
    36 Kaohsiung Taiwan
    37 Taipei City Taiwan 10002
    38 London United Kingdom E1 1BB
    39 London United Kingdom

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02979613
    Other Study ID Numbers:
    • GS-US-320-4018
    • 2016-003632-20
    First Posted:
    Dec 1, 2016
    Last Update Posted:
    Sep 14, 2020
    Last Verified:
    Aug 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis B, Chronic
    Hepatitis
    Hepatitis, Chronic

    Study Results

    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 Detail 541 participants were screened.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description Participants who were virologically suppressed and taking tenofovir disoproxil fumarate (TDF) 300 mg tablet orally once daily received tenofovir alafenamide (TAF) 25 mg tablet orally once daily, and placebo to match TDF once daily for up to 53 weeks in the double-blind (DB) phase. Participants who completed DB treatment and were willing to enter in the open-label extension (OLE) phase, received TAF 25 mg tablet orally once daily for up to 52 weeks. 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.
    Period Title: Double-Blind Phase
    STARTED 245 245
    COMPLETED 235 237
    NOT COMPLETED 10 8
    Period Title: Double-Blind Phase
    STARTED 235 237
    COMPLETED 232 231
    NOT COMPLETED 3 6

    Baseline Characteristics

    Arm/Group Title TAF 25 mg TDF 300 mg Total
    Arm/Group Description 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. 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. Total of all reporting groups
    Overall Participants 243 245 488
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51
    (10.5)
    51
    (10.8)
    51
    (10.7)
    Age, Customized (Count of Participants)
    < 50 Years
    107
    44%
    109
    44.5%
    216
    44.3%
    ≥ 50 Years
    136
    56%
    136
    55.5%
    272
    55.7%
    Sex: Female, Male (Count of Participants)
    Female
    64
    26.3%
    79
    32.2%
    143
    29.3%
    Male
    179
    73.7%
    166
    67.8%
    345
    70.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    1.2%
    0
    0%
    3
    0.6%
    Not Hispanic or Latino
    240
    98.8%
    245
    100%
    485
    99.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    195
    80.2%
    205
    83.7%
    400
    82%
    Black or African American
    9
    3.7%
    8
    3.3%
    17
    3.5%
    Native Hawaiian or Pacific Islander
    0
    0%
    1
    0.4%
    1
    0.2%
    White
    38
    15.6%
    31
    12.7%
    69
    14.1%
    Other
    1
    0.4%
    0
    0%
    1
    0.2%
    Region of Enrollment (Count of Participants)
    Canada
    42
    17.3%
    47
    19.2%
    89
    18.2%
    South Korea
    61
    25.1%
    77
    31.4%
    138
    28.3%
    Hong Kong
    15
    6.2%
    13
    5.3%
    28
    5.7%
    United States
    63
    25.9%
    64
    26.1%
    127
    26%
    Taiwan
    28
    11.5%
    13
    5.3%
    41
    8.4%
    Italy
    9
    3.7%
    12
    4.9%
    21
    4.3%
    United Kingdom
    6
    2.5%
    7
    2.9%
    13
    2.7%
    Spain
    19
    7.8%
    12
    4.9%
    31
    6.4%
    Alanine Aminotransferase (ALT) (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    28
    (15.6)
    26
    (12.0)
    27
    (13.9)
    ALT Level Based on Central Lab Normal Range (Count of Participants)
    ≤ ULN
    211
    86.8%
    226
    92.2%
    437
    89.5%
    > ULN to 5xULN
    32
    13.2%
    19
    7.8%
    51
    10.5%
    > 5xULN
    0
    0%
    0
    0%
    0
    0%
    ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range (Count of Participants)
    ≤ ULN
    191
    78.6%
    192
    78.4%
    383
    78.5%
    > ULN to 5xULN
    52
    21.4%
    53
    21.6%
    105
    21.5%
    > 5xULN
    0
    0%
    0
    0%
    0
    0%
    Hepatitis B virus (HBV) DNA Category (Count of Participants)
    < 20 IU/mL
    238
    97.9%
    242
    98.8%
    480
    98.4%
    20 to < 69 IU/mL
    2
    0.8%
    3
    1.2%
    5
    1%
    ≥ 69 IU/mL
    3
    1.2%
    0
    0%
    3
    0.6%
    Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status (Count of Participants)
    Positive/Negative
    78
    32.1%
    78
    31.8%
    156
    32%
    Positive/Positive
    0
    0%
    1
    0.4%
    1
    0.2%
    Negative/Negative
    17
    7%
    28
    11.4%
    45
    9.2%
    Negative/Positive
    148
    60.9%
    138
    56.3%
    286
    58.6%
    FibroTest® Score (scores on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [scores on a scale]
    0.42
    (0.234)
    0.41
    (0.211)
    0.42
    (0.223)
    Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) (mL/min) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mL/min]
    95.0
    (25.58)
    93.8
    (25.16)
    94.4
    (25.35)
    Hip Bone Mineral Density (BMD) Status (Count of Participants)
    Normal (T-score ≥ -1.0)
    143
    58.8%
    124
    50.6%
    267
    54.7%
    Osteopenia (-2.5 ≤ T-score < -1.0)
    89
    36.6%
    116
    47.3%
    205
    42%
    Osteoporosis (T-score < -2.5)
    9
    3.7%
    4
    1.6%
    13
    2.7%
    Spine BMD Status (Count of Participants)
    Normal (T-score ≥ -1.0)
    125
    51.4%
    120
    49%
    245
    50.2%
    Osteopenia (-2.5 ≤ T-score < -1.0)
    90
    37%
    97
    39.6%
    187
    38.3%
    Osteoporosis (T-score < -2.5)
    28
    11.5%
    28
    11.4%
    56
    11.5%

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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: 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 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Number [percentage of participants]
    0.4
    0.2%
    0.4
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments 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.
    Type of Statistical Test Non-Inferiority
    Comments Non-inferiority was assessed using a 95% confidence interval (CI) approach, with a non-inferiority margin of 4%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -1.9 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted Mantel-Haenszel (MH) percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    2. Secondary Outcome
    Title Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm
    Description 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: 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 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Number [percentage of participants]
    0.4
    0.2%
    0.4
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Non-Inferiority
    Comments Non-inferiority was assessed using a 95% confidence interval (CI) approach, with a non-inferiority margin of 4%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -1.9 to 1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9953
    Comments P-value for the superiority tests compared the percentage of each HBV DNA outcome was from CMH tests stratified by baseline age groups and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    3. Secondary Outcome
    Title Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Number [percentage of participants]
    96.3
    39.6%
    96.3
    39.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Non-Inferiority
    Comments Non-inferiority was assessed using a 95% CI approach, with a non-inferiority margin of 4%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -3.7 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.98
    Comments P-value for the superiority tests compared the percentage of each HBV DNA outcome was from CMH tests stratified by baseline age groups and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    4. Secondary Outcome
    Title Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    M = F Approach: < 20 IU/mL Target Not Detected
    63.4
    26.1%
    62.0
    25.3%
    M = F Approach: < 20 IU/mL Target Detected
    32.9
    13.5%
    34.3
    14%
    M = E Approach: < 20 IU/mL Target Not Detected
    65.5
    27%
    64.1
    26.2%
    M = E Approach: < 20 IU/mL Target Detected
    34.0
    14%
    35.4
    14.4%
    5. Secondary Outcome
    Title Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Number [percentage of participants]
    94.7
    39%
    93.9
    38.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Non-Inferiority
    Comments Non-inferiority was assessed using a 95% confidence interval (CI) approach, with a non-inferiority margin of 4%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95.0%
    -3.5 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6863
    Comments P-value for the superiority tests compared the percentage of each HBV DNA outcome was from CMH tests stratified by baseline age groups and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    6. Secondary Outcome
    Title Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    M = F Approach: < 20 IU/mL Target Not Detected
    65.8
    27.1%
    66.1
    27%
    M = F Approach: < 20 IU/mL Target Detected
    28.8
    11.9%
    27.8
    11.3%
    M = E Approach: < 20 IU/mL Target Not Detected
    69.3
    28.5%
    70.1
    28.6%
    M = E Approach: < 20 IU/mL Target Detected
    30.3
    12.5%
    29.4
    12%
    7. Secondary Outcome
    Title Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 78 78
    Number [percentage of participants]
    7.7
    3.2%
    6.4
    2.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7258
    Comments P-value was from the CMH test, stratified by baseline age groups (< 50, ≥ 50 years).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -7.2 to 10.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between the treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups.
    8. Secondary Outcome
    Title Percentage of Participants With HBeAg Seroconversion at Week 48
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 78 78
    Number [percentage of participants]
    2.6
    1.1%
    0.0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1348
    Comments P-value was from the CMH test, stratified by baseline age groups (< 50, ≥ 50 years).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 2.7
    Confidence Interval (2-Sided) 95%
    -2.3 to 7.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between the treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups.
    9. Secondary Outcome
    Title Percentage of Participants With HBeAg Loss at Week 96
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 78 78
    Number [percentage of participants]
    17.9
    7.4%
    9.0
    3.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1005
    Comments P-value was from CMH tests stratified by baseline age groups (< 50, ≥ 50 years).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 9.0
    Confidence Interval (2-Sided) 95%
    -2.0 to 20.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups.
    10. Secondary Outcome
    Title Percentage of Participants With HBeAg Seroconversion at Week 96
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 78 78
    Number [percentage of participants]
    5.1
    2.1%
    2.6
    1.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4154
    Comments P-value was from CMH tests stratified by baseline age groups (< 50, ≥ 50 years).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 2.5
    Confidence Interval (2-Sided) 95%
    -4.5 to 9.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups.
    11. Secondary Outcome
    Title Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Number [percentage of participants]
    0.0
    0%
    2.0
    0.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0281
    Comments P-value was from the CMH test, stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -4.4 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between the treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    12. Secondary Outcome
    Title Percentage of Participants With HBsAg Seroconversion at Week 48
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Number [percentage of participants]
    0.0
    0%
    0.0
    0%
    13. Secondary Outcome
    Title Percentage of Participants With HBsAg Loss at Week 96
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Number [percentage of participants]
    1.6
    0.7%
    2.4
    1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5373
    Comments P-value was from CMH tests stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -3.7 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    14. Secondary Outcome
    Title Percentage of Participants With HBsAg Seroconversion at Week 96
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Number [percentage of participants]
    0.8
    0.3%
    0.4
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5845
    Comments P-value was from CMH tests stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -1.7 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    15. Secondary Outcome
    Title 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)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Central Laboratory Criteria
    89.3
    36.7%
    84.9
    34.7%
    AASLD Criteria
    79.0
    32.5%
    75.1
    30.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments Central Laboratory Criteria
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1405
    Comments P-value was from the CMH test, stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 4.5
    Confidence Interval (2-Sided) 95%
    -1.6 to 10.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between the treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments AASLD Criteria
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3133
    Comments P-value was from the CMH test, stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 3.8
    Confidence Interval (2-Sided) 95%
    -3.7 to 11.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between the treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    16. Secondary Outcome
    Title Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 52 53
    Central Laboratory Criteria
    50.0
    20.6%
    36.8
    15%
    AASLD Criteria
    50.0
    20.6%
    26.4
    10.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments Central Laboratory criteria
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3381
    Comments P-value was from the CMH test, stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 14.1
    Confidence Interval (2-Sided) 95%
    -16.4 to 44.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between the treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments AASLD Criteria
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0136
    Comments P-value was from the CMH test, stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value 23.8
    Confidence Interval (2-Sided) 95%
    5.3 to 42.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentage of participants between the treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    17. Secondary Outcome
    Title Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 243 245
    Central Laboratory Criteria
    88.5
    36.4%
    91.4
    37.3%
    AASLD Criteria
    80.7
    33.2%
    86.5
    35.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments Central Laboratory Criteria
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2803
    Comments P-value was from CMH tests stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value -2.9
    Confidence Interval (2-Sided) 95%
    -8.4 to 2.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments AASLD Criteria
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0788
    Comments P-value was from CMH tests stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value -5.9
    Confidence Interval (2-Sided) 95%
    -12.6 to 0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    18. Secondary Outcome
    Title Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 52 53
    Central Laboratory Criteria
    56.3
    23.2%
    78.9
    32.2%
    AASLD Criteria
    55.8
    23%
    73.6
    30%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments Central Laboratory Criteria
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0880
    Comments P-value was from CMH tests stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value -23.9
    Confidence Interval (2-Sided) 95%
    -51.2 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments AASLD Criteria
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0510
    Comments P-value was from CMH tests stratified by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in the Percentages
    Estimated Value -18.6
    Confidence Interval (2-Sided) 95.0%
    -37.4 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in the percentages of participants between treatment groups and its 95% CI were calculated based on the stratum-adjusted MH percentage, adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata.
    19. Secondary Outcome
    Title Change From Baseline in FibroTest® Score at Week 48
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 234 236
    Mean (Standard Deviation) [scores on a scale]
    -0.02
    (0.082)
    -0.01
    (0.082)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0186
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -0.03 to 0.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    20. Secondary Outcome
    Title Change From Baseline in FibroTest® Score at Week 96
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed. Participants were analyzed according to the treatment to which they were randomized.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 231 232
    Mean (Standard Deviation) [scores on a scale]
    -0.03
    (0.080)
    -0.03
    (0.090)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6956
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value 0.00
    Confidence Interval (2-Sided) 95%
    -0.02 to 0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    21. Secondary Outcome
    Title Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
    Description Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 225 226
    Mean (Standard Deviation) [percent change]
    0.659
    (2.0818)
    -0.507
    (1.9051)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value 1.167
    Confidence Interval (2-Sided) 95%
    0.797 to 1.536
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    22. Secondary Outcome
    Title Percent Change From Baseline in Hip BMD at Week 96
    Description Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
    Time Frame Baseline; Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Hip DXA Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 227 224
    Mean (Standard Deviation) [percent change]
    1.157
    (2.8501)
    0.180
    (2.6813)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value 0.977
    Confidence Interval (2-Sided) 95%
    0.465 to 1.490
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    23. Secondary Outcome
    Title Percent Change From Baseline in Spine BMD at Week 48
    Description Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
    Time Frame Baseline; Week 48

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 227 229
    Mean (Standard Deviation) [percent change]
    1.743
    (3.4674)
    -0.138
    (3.1072)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value 1.881
    Confidence Interval (2-Sided) 95%
    1.275 to 2.486
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    24. Secondary Outcome
    Title Percent Change From Baseline in Spine BMD at Week 96
    Description Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
    Time Frame Baseline; Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Spine DXA Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 229 227
    Mean (Standard Deviation) [percent change]
    2.330
    (3.9301)
    1.726
    (3.8224)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0970
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value 0.604
    Confidence Interval (2-Sided) 95%
    -0.110 to 1.317
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    25. Secondary Outcome
    Title Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 234 237
    Median (Inter-Quartile Range) [mL/min]
    2.240
    -1.722
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-values were from the 2-sided Wilcoxon rank sum test to compare the 2 treatment groups.
    Method Wilcoxon rank sum test
    Comments
    26. Secondary Outcome
    Title Change From Baseline in eGFR-CG at Week 96
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.
    Arm/Group Title TAF 25 mg TDF 300 mg
    Arm/Group Description 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. 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.
    Measure Participants 232 232
    Median (Inter-Quartile Range) [mL/min]
    1.626
    0.544
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TAF 25 mg, TDF 300 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7535
    Comments P-values were from the 2-sided Wilcoxon rank sum test to compare the 2 treatment groups.
    Method Wilcoxon rank sum test
    Comments

    Adverse Events

    Time Frame All-Cause Mortality: First dose date up to 161 weeks (up to approximately 3 years); Adverse Events: First dose date up to the last dose (maximum: 105 weeks) plus 3 days
    Adverse Event Reporting Description The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title TAF 25 mg TDF 300 mg OLE TAF 25 mg From TAF 25 mg OLE TAF 25 mg From TDF 300 mg
    Arm/Group Description Adverse events reported in this group occurred during the DB phase. 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. Adverse events reported in this group occurred during the DB phase. 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. Adverse events reported in this group occurred during the OLE phase. Participants who completed TAF treatment in the DB phase and were willing to enter in the OLE phase, received TAF 25 mg tablet orally once daily for up to 52 weeks. Adverse events reported in this group occurred during the OLE phase. Participants who completed TDF treatment in the DB phase and were willing to enter in the OLE phase, received TAF 25 mg tablet orally once daily for up to 52 weeks.
    All Cause Mortality
    TAF 25 mg TDF 300 mg OLE TAF 25 mg From TAF 25 mg OLE TAF 25 mg From TDF 300 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/243 (0%) 0/245 (0%) 0/235 (0%) 1/237 (0.4%)
    Serious Adverse Events
    TAF 25 mg TDF 300 mg OLE TAF 25 mg From TAF 25 mg OLE TAF 25 mg From TDF 300 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/243 (4.5%) 3/245 (1.2%) 8/235 (3.4%) 5/237 (2.1%)
    Cardiac disorders
    Acute myocardial infarction 0/243 (0%) 0/245 (0%) 0/235 (0%) 1/237 (0.4%)
    Angina pectoris 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Atrial fibrillation 0/243 (0%) 0/245 (0%) 0/235 (0%) 1/237 (0.4%)
    Cardiac arrest 0/243 (0%) 0/245 (0%) 0/235 (0%) 1/237 (0.4%)
    Gastrointestinal disorders
    Pancreatic mass 0/243 (0%) 0/245 (0%) 1/235 (0.4%) 0/237 (0%)
    Pancreatitis 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Immune system disorders
    Anaphylactic reaction 0/243 (0%) 0/245 (0%) 1/235 (0.4%) 0/237 (0%)
    Infections and infestations
    Herpes zoster 0/243 (0%) 1/245 (0.4%) 0/235 (0%) 0/237 (0%)
    Necrotising fasciitis 0/243 (0%) 0/245 (0%) 1/235 (0.4%) 0/237 (0%)
    Pneumonia necrotising 0/243 (0%) 0/245 (0%) 0/235 (0%) 1/237 (0.4%)
    Injury, poisoning and procedural complications
    Muscle rupture 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Tendon injury 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Wrist fracture 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/243 (0%) 0/245 (0%) 1/235 (0.4%) 0/237 (0%)
    Rotator cuff syndrome 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Hepatocellular carcinoma 1/243 (0.4%) 1/245 (0.4%) 2/235 (0.9%) 0/237 (0%)
    Lipoma 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Lung squamous cell carcinoma stage II 0/243 (0%) 0/245 (0%) 1/235 (0.4%) 0/237 (0%)
    Testicular neoplasm 0/243 (0%) 0/245 (0%) 0/235 (0%) 1/237 (0.4%)
    Psychiatric disorders
    Bipolar I disorder 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Homicidal ideation 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Suicidal ideation 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Renal and urinary disorders
    Calculus bladder 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Reproductive system and breast disorders
    Cervical dysplasia 1/243 (0.4%) 0/245 (0%) 0/235 (0%) 0/237 (0%)
    Prostatitis 0/243 (0%) 0/245 (0%) 1/235 (0.4%) 0/237 (0%)
    Vascular disorders
    Varicose vein 0/243 (0%) 1/245 (0.4%) 0/235 (0%) 0/237 (0%)
    Other (Not Including Serious) Adverse Events
    TAF 25 mg TDF 300 mg OLE TAF 25 mg From TAF 25 mg OLE TAF 25 mg From TDF 300 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 31/243 (12.8%) 28/245 (11.4%) 15/235 (6.4%) 15/237 (6.3%)
    Infections and infestations
    Upper respiratory tract infection 18/243 (7.4%) 16/245 (6.5%) 11/235 (4.7%) 12/237 (5.1%)
    Nasopharyngitis 13/243 (5.3%) 12/245 (4.9%) 4/235 (1.7%) 3/237 (1.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02979613
    Other Study ID Numbers:
    • GS-US-320-4018
    • 2016-003632-20
    First Posted:
    Dec 1, 2016
    Last Update Posted:
    Sep 14, 2020
    Last Verified:
    Aug 1, 2020