Trial Outcomes & Findings for Study to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed (NCT NCT02979613)

Last Updated: 2020-09-14

Results Overview

The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and * Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

490 participants

Primary outcome timeframe

Week 48

Results posted on

2020-09-14

Participant Flow

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.

541 participants were screened.

Participant milestones

Participant milestones
Measure	TAF 25 mg 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.	TDF 300 mg Participants who were virologically suppressed and taking TDF 300 mg tablet orally once daily received TDF 300 mg tablet orally once daily, and placebo to match TAF once daily for up to 50 weeks in the DB phase. Participants who completed DB treatment and were willing to enter in the OLE phase, received TAF 25 mg tablet orally once daily for up to 52 weeks.
Double-Blind Phase STARTED	245	245
Double-Blind Phase COMPLETED	235	237
Double-Blind Phase NOT COMPLETED	10	8
Open-Label Extension (OLE) Phase STARTED	235	237
Open-Label Extension (OLE) Phase COMPLETED	232	231
Open-Label Extension (OLE) Phase NOT COMPLETED	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	TAF 25 mg 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.	TDF 300 mg Participants who were virologically suppressed and taking TDF 300 mg tablet orally once daily received TDF 300 mg tablet orally once daily, and placebo to match TAF once daily for up to 50 weeks in the DB phase. Participants who completed DB treatment and were willing to enter in the OLE phase, received TAF 25 mg tablet orally once daily for up to 52 weeks.
Double-Blind Phase Withdrew Consent	2	4
Double-Blind Phase Pregnancy	2	2
Double-Blind Phase Adverse Event	2	0
Double-Blind Phase Lost to Follow-up	1	1
Double-Blind Phase Protocol Violation	1	1
Double-Blind Phase Randomized but Never Treated	2	0
Open-Label Extension (OLE) Phase Withdrew Consent	2	4
Open-Label Extension (OLE) Phase Adverse Event	1	0
Open-Label Extension (OLE) Phase Death	0	1
Open-Label Extension (OLE) Phase Investigator's Discretion	0	1

Baseline Characteristics

Participants in Safety Analysis Set with available data were analyzed.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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 n=488 Participants Total of all reporting groups
Age, Continuous	51 years STANDARD_DEVIATION 10.5 • n=243 Participants	51 years STANDARD_DEVIATION 10.8 • n=245 Participants	51 years STANDARD_DEVIATION 10.7 • n=488 Participants
Age, Customized < 50 Years	107 Participants n=243 Participants	109 Participants n=245 Participants	216 Participants n=488 Participants
Age, Customized ≥ 50 Years	136 Participants n=243 Participants	136 Participants n=245 Participants	272 Participants n=488 Participants
Sex: Female, Male Female	64 Participants n=243 Participants	79 Participants n=245 Participants	143 Participants n=488 Participants
Sex: Female, Male Male	179 Participants n=243 Participants	166 Participants n=245 Participants	345 Participants n=488 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=243 Participants	0 Participants n=245 Participants	3 Participants n=488 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	240 Participants n=243 Participants	245 Participants n=245 Participants	485 Participants n=488 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=243 Participants	0 Participants n=245 Participants	0 Participants n=488 Participants
Race/Ethnicity, Customized Race · Asian	195 Participants n=243 Participants	205 Participants n=245 Participants	400 Participants n=488 Participants
Race/Ethnicity, Customized Race · Black or African American	9 Participants n=243 Participants	8 Participants n=245 Participants	17 Participants n=488 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Pacific Islander	0 Participants n=243 Participants	1 Participants n=245 Participants	1 Participants n=488 Participants
Race/Ethnicity, Customized Race · White	38 Participants n=243 Participants	31 Participants n=245 Participants	69 Participants n=488 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=243 Participants	0 Participants n=245 Participants	1 Participants n=488 Participants
Region of Enrollment Canada	42 Participants n=243 Participants	47 Participants n=245 Participants	89 Participants n=488 Participants
Region of Enrollment South Korea	61 Participants n=243 Participants	77 Participants n=245 Participants	138 Participants n=488 Participants
Region of Enrollment Hong Kong	15 Participants n=243 Participants	13 Participants n=245 Participants	28 Participants n=488 Participants
Region of Enrollment United States	63 Participants n=243 Participants	64 Participants n=245 Participants	127 Participants n=488 Participants
Region of Enrollment Taiwan	28 Participants n=243 Participants	13 Participants n=245 Participants	41 Participants n=488 Participants
Region of Enrollment Italy	9 Participants n=243 Participants	12 Participants n=245 Participants	21 Participants n=488 Participants
Region of Enrollment United Kingdom	6 Participants n=243 Participants	7 Participants n=245 Participants	13 Participants n=488 Participants
Region of Enrollment Spain	19 Participants n=243 Participants	12 Participants n=245 Participants	31 Participants n=488 Participants
Alanine Aminotransferase (ALT)	28 U/L STANDARD_DEVIATION 15.6 • n=243 Participants	26 U/L STANDARD_DEVIATION 12.0 • n=245 Participants	27 U/L STANDARD_DEVIATION 13.9 • n=488 Participants
ALT Level Based on Central Lab Normal Range ≤ ULN	211 Participants n=243 Participants	226 Participants n=245 Participants	437 Participants n=488 Participants
ALT Level Based on Central Lab Normal Range > ULN to 5xULN	32 Participants n=243 Participants	19 Participants n=245 Participants	51 Participants n=488 Participants
ALT Level Based on Central Lab Normal Range > 5xULN	0 Participants n=243 Participants	0 Participants n=245 Participants	0 Participants n=488 Participants
ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range ≤ ULN	191 Participants n=243 Participants	192 Participants n=245 Participants	383 Participants n=488 Participants
ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range > ULN to 5xULN	52 Participants n=243 Participants	53 Participants n=245 Participants	105 Participants n=488 Participants
ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range > 5xULN	0 Participants n=243 Participants	0 Participants n=245 Participants	0 Participants n=488 Participants
Hepatitis B virus (HBV) DNA Category < 20 IU/mL	238 Participants n=243 Participants	242 Participants n=245 Participants	480 Participants n=488 Participants
Hepatitis B virus (HBV) DNA Category 20 to < 69 IU/mL	2 Participants n=243 Participants	3 Participants n=245 Participants	5 Participants n=488 Participants
Hepatitis B virus (HBV) DNA Category ≥ 69 IU/mL	3 Participants n=243 Participants	0 Participants n=245 Participants	3 Participants n=488 Participants
Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Positive/Negative	78 Participants n=243 Participants	78 Participants n=245 Participants	156 Participants n=488 Participants
Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Positive/Positive	0 Participants n=243 Participants	1 Participants n=245 Participants	1 Participants n=488 Participants
Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Negative/Negative	17 Participants n=243 Participants	28 Participants n=245 Participants	45 Participants n=488 Participants
Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Negative/Positive	148 Participants n=243 Participants	138 Participants n=245 Participants	286 Participants n=488 Participants
FibroTest® Score	0.42 scores on a scale STANDARD_DEVIATION 0.234 • n=241 Participants • Participants in Safety Analysis Set with available data were analyzed.	0.41 scores on a scale STANDARD_DEVIATION 0.211 • n=245 Participants • Participants in Safety Analysis Set with available data were analyzed.	0.42 scores on a scale STANDARD_DEVIATION 0.223 • n=486 Participants • Participants in Safety Analysis Set with available data were analyzed.
Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)	95.0 mL/min STANDARD_DEVIATION 25.58 • n=243 Participants	93.8 mL/min STANDARD_DEVIATION 25.16 • n=245 Participants	94.4 mL/min STANDARD_DEVIATION 25.35 • n=488 Participants
Hip Bone Mineral Density (BMD) Status Normal (T-score ≥ -1.0)	143 Participants n=241 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.	124 Participants n=244 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.	267 Participants n=485 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.
Hip Bone Mineral Density (BMD) Status Osteopenia (-2.5 ≤ T-score < -1.0)	89 Participants n=241 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.	116 Participants n=244 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.	205 Participants n=485 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.
Hip Bone Mineral Density (BMD) Status Osteoporosis (T-score < -2.5)	9 Participants n=241 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.	4 Participants n=244 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.	13 Participants n=485 Participants • Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, and had nonmissing baseline hip BMD values.
Spine BMD Status Normal (T-score ≥ -1.0)	125 Participants n=243 Participants	120 Participants n=245 Participants	245 Participants n=488 Participants
Spine BMD Status Osteopenia (-2.5 ≤ T-score < -1.0)	90 Participants n=243 Participants	97 Participants n=245 Participants	187 Participants n=488 Participants
Spine BMD Status Osteoporosis (T-score < -2.5)	28 Participants n=243 Participants	28 Participants n=245 Participants	56 Participants n=488 Participants

PRIMARY outcome

Timeframe: Week 48

Population: The Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug. Participants were analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm	0.4 percentage of participants	0.4 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.

The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 96 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 96 analysis window (from Day 589 to Day 840, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 96 analysis window and * Discontinued study drug prior to or in the Week 96 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 96 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm	0.4 percentage of participants	0.4 percentage of participants

SECONDARY outcome

Timeframe: Weeks 48

Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48	96.3 percentage of participants	96.3 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 M = F Approach: < 20 IU/mL Target Not Detected	63.4 percentage of participants	62.0 percentage of participants
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 M = F Approach: < 20 IU/mL Target Detected	32.9 percentage of participants	34.3 percentage of participants
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 M = E Approach: < 20 IU/mL Target Not Detected	65.5 percentage of participants	64.1 percentage of participants
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48 M = E Approach: < 20 IU/mL Target Detected	34.0 percentage of participants	35.4 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96	94.7 percentage of participants	93.9 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 M = F Approach: < 20 IU/mL Target Not Detected	65.8 percentage of participants	66.1 percentage of participants
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 M = F Approach: < 20 IU/mL Target Detected	28.8 percentage of participants	27.8 percentage of participants
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 M = E Approach: < 20 IU/mL Target Not Detected	69.3 percentage of participants	70.1 percentage of participants
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96 M = E Approach: < 20 IU/mL Target Detected	30.3 percentage of participants	29.4 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: The Serologically Evaluable Full Analysis Set for HBeAg loss and seroconversion included all participants who were randomized and received at least 1 dose of study drug and were HBeAg-positive and HBeAb-negative or had a missing value at baseline. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=78 Participants 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.	TDF 300 mg n=78 Participants 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.
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48	7.7 percentage of participants	6.4 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Serologically Evaluable Full Analysis Set for HBeAg loss and seroconversion were analyzed. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=78 Participants 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.	TDF 300 mg n=78 Participants 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.
Percentage of Participants With HBeAg Seroconversion at Week 48	2.6 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=78 Participants 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.	TDF 300 mg n=78 Participants 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.
Percentage of Participants With HBeAg Loss at Week 96	17.9 percentage of participants	9.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=78 Participants 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.	TDF 300 mg n=78 Participants 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.
Percentage of Participants With HBeAg Seroconversion at Week 96	5.1 percentage of participants	2.6 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: The Serologically Evaluable Full Analysis Set for HBsAg loss and seroconversion included all participants who were randomized and received at least 1 dose of study drug and were HBsAg-positive and HBsAb-negative or had a missing value at baseline. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48	0.0 percentage of participants	2.0 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Serologically Evaluable Full Analysis Set for HBsAg loss and seroconversion were analyzed. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With HBsAg Seroconversion at Week 48	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With HBsAg Loss at Week 96	1.6 percentage of participants	2.4 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With HBsAg Seroconversion at Week 96	0.8 percentage of participants	0.4 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria) Central Laboratory Criteria	89.3 percentage of participants	84.9 percentage of participants
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria) AASLD Criteria	79.0 percentage of participants	75.1 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Full Analysis Set with Baseline ALT \> ULN were analyzed. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=52 Participants 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.	TDF 300 mg n=53 Participants 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.
Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria) Central Laboratory Criteria	50.0 percentage of participants	36.8 percentage of participants
Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria) AASLD Criteria	50.0 percentage of participants	26.4 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set were analyzed. Participants were analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=243 Participants 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.	TDF 300 mg n=245 Participants 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.
Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria) Central Laboratory Criteria	88.5 percentage of participants	91.4 percentage of participants
Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria) AASLD Criteria	80.7 percentage of participants	86.5 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set with Baseline ALT \> ULN were analyzed. Participants were analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=52 Participants 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.	TDF 300 mg n=53 Participants 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.
Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria) Central Laboratory Criteria	56.3 percentage of participants	78.9 percentage of participants
Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria) AASLD Criteria	55.8 percentage of participants	73.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Full Analysis Set with available data were analyzed. Participants were analyzed according to the treatment to which they were randomized.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=234 Participants 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.	TDF 300 mg n=236 Participants 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.
Change From Baseline in FibroTest® Score at Week 48	-0.02 scores on a scale Standard Deviation 0.082	-0.01 scores on a scale Standard Deviation 0.082

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Full Analysis Set with available data were analyzed. Participants were analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=231 Participants 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.	TDF 300 mg n=232 Participants 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.
Change From Baseline in FibroTest® Score at Week 96	-0.03 scores on a scale Standard Deviation 0.080	-0.03 scores on a scale Standard Deviation 0.090

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Hip DXA Analysis Set (included all participants who were randomized into the study, received at least 1 dose of study drug, and had non-missing baseline hip BMD values) with available data were analysed. Participants were analyzed according to the treatment they actually received.

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

Outcome measures

Outcome measures
Measure	TAF 25 mg n=225 Participants 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.	TDF 300 mg n=226 Participants 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.
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	0.659 percent change Standard Deviation 2.0818	-0.507 percent change Standard Deviation 1.9051

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Hip DXA Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.

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

Outcome measures

Outcome measures
Measure	TAF 25 mg n=227 Participants 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.	TDF 300 mg n=224 Participants 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.
Percent Change From Baseline in Hip BMD at Week 96	1.157 percent change Standard Deviation 2.8501	0.180 percent change Standard Deviation 2.6813

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Spine DXA Analysis Set (included all participants who were randomized into the study, received at least 1 dose of study drug, and had non-missing baseline spine BMD values) with available data were analysed. Participants were analyzed according to the treatment they actually received.

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

Outcome measures

Outcome measures
Measure	TAF 25 mg n=227 Participants 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.	TDF 300 mg n=229 Participants 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.
Percent Change From Baseline in Spine BMD at Week 48	1.743 percent change Standard Deviation 3.4674	-0.138 percent change Standard Deviation 3.1072

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Spine DXA Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.

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

Outcome measures

Outcome measures
Measure	TAF 25 mg n=229 Participants 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.	TDF 300 mg n=227 Participants 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.
Percent Change From Baseline in Spine BMD at Week 96	2.330 percent change Standard Deviation 3.9301	1.726 percent change Standard Deviation 3.8224

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Safety Analysis Set (included all randomized participants who received at least 1 dose of study drug) with available data were analyzed. Participants were analyzed according to the treatment they actually received.

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.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=234 Participants 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.	TDF 300 mg n=237 Participants 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.
Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48	2.240 mL/min Interval -3.957 to 7.704	-1.722 mL/min Interval -7.02 to 2.634

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Safety Analysis Set with available data were analyzed. Participants were analyzed according to the treatment they actually received.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=232 Participants 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.	TDF 300 mg n=232 Participants 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.
Change From Baseline in eGFR-CG at Week 96	1.626 mL/min Interval -4.58 to 6.952	0.544 mL/min Interval -5.227 to 7.678

Adverse Events

TAF 25 mg

Serious events: 11 serious events

Other events: 31 other events

Deaths: 0 deaths

TDF 300 mg

Serious events: 3 serious events

Other events: 28 other events

Deaths: 0 deaths

OLE TAF 25 mg From TAF 25 mg

Serious events: 8 serious events

Other events: 15 other events

Deaths: 0 deaths

OLE TAF 25 mg From TDF 300 mg

Serious events: 5 serious events

Other events: 15 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	TAF 25 mg n=243 participants at risk 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.	TDF 300 mg n=245 participants at risk 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.	OLE TAF 25 mg From TAF 25 mg n=235 participants at risk 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.	OLE TAF 25 mg From TDF 300 mg n=237 participants at risk 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.
Infections and infestations Upper respiratory tract infection	7.4% 18/243 • 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 The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.	6.5% 16/245 • 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 The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.	4.7% 11/235 • 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 The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.	5.1% 12/237 • 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 The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	5.3% 13/243 • 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 The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.	4.9% 12/245 • 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 The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.	1.7% 4/235 • 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 The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.	1.3% 3/237 • 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 The Safety Analysis Set included all randomized participants who received at least 1 dose of study drug.

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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
Publication restrictions are in place

Restriction type: OTHER