Trial Outcomes & Findings for Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Positive for Hepatitis B e Antigen (NCT NCT01940471)

NCT ID: NCT01940471

Last Updated: 2023-10-10

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

875 participants

Primary outcome timeframe

Week 48

Results posted on

2023-10-10

Participant Flow

Participants were enrolled at study sites in East Asia, Europe, North America, Australia, India, and New Zealand.

1396 participants were screened.

Participant milestones

Participant milestones
Measure	TAF 25 mg Tenofovir alafenamide (Vemlidy®; TAF) 25 mg tablet + tenofovir disoproxil fumarate (Viread®; TDF) placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TDF 300 mg TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TAF 25 mg to TAF 25 mg After Week 96 or 144 in the Blinded Treatment Phase, participants were given the option to continue with Open-label (OL) TAF 25 mg for additional 288 or 240 weeks (Up to Week 384), respectively. After the completion of OL TAF Extension Phase treatment or when there was early discontinuation of treatment, participants either switched to commercially available anti-HBV treatments in their country or entered follow-up phase and were followed-up every 4 weeks for 24 weeks off treatment (treatment-free follow-up \[TFFU\]) for the assessment of safety.	TDF 300 mg to TAF 25 mg After Week 96 or 144 in the Blinded Treatment Phase, participants were given the option to switch to OL TAF 25 mg for additional 288 or 240 weeks (Up to Week 384), respectively. After the completion of OL TAF Extension Phase treatment or when there was early discontinuation of treatment, participants either switched to commercially available anti-HBV treatments in their country or entered follow-up phase and were followed-up every 4 weeks for 24 weeks off treatment (TFFU) for the assessment of safety.
Period 1: Double-blind Phase STARTED	582	293	0	0
Period 1: Double-blind Phase COMPLETED	515	253	0	0
Period 1: Double-blind Phase NOT COMPLETED	67	40	0	0
Period 2: Open-Label TAF Extension Phase STARTED	0	0	514	253
Period 2: Open-Label TAF Extension Phase COMPLETED	0	0	422	213
Period 2: Open-Label TAF Extension Phase NOT COMPLETED	0	0	92	40

Reasons for withdrawal

Reasons for withdrawal
Measure	TAF 25 mg Tenofovir alafenamide (Vemlidy®; TAF) 25 mg tablet + tenofovir disoproxil fumarate (Viread®; TDF) placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TDF 300 mg TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TAF 25 mg to TAF 25 mg After Week 96 or 144 in the Blinded Treatment Phase, participants were given the option to continue with Open-label (OL) TAF 25 mg for additional 288 or 240 weeks (Up to Week 384), respectively. After the completion of OL TAF Extension Phase treatment or when there was early discontinuation of treatment, participants either switched to commercially available anti-HBV treatments in their country or entered follow-up phase and were followed-up every 4 weeks for 24 weeks off treatment (treatment-free follow-up \[TFFU\]) for the assessment of safety.	TDF 300 mg to TAF 25 mg After Week 96 or 144 in the Blinded Treatment Phase, participants were given the option to switch to OL TAF 25 mg for additional 288 or 240 weeks (Up to Week 384), respectively. After the completion of OL TAF Extension Phase treatment or when there was early discontinuation of treatment, participants either switched to commercially available anti-HBV treatments in their country or entered follow-up phase and were followed-up every 4 weeks for 24 weeks off treatment (TFFU) for the assessment of safety.
Period 1: Double-blind Phase Withdrew Consent	31	18	0	0
Period 1: Double-blind Phase Lost to Follow-up	8	6	0	0
Period 1: Double-blind Phase Investigator's Discretion	8	5	0	0
Period 1: Double-blind Phase Pregnancy	9	2	0	0
Period 1: Double-blind Phase Non-Compliance with Study Drug	3	2	0	0
Period 1: Double-blind Phase Adverse Event	2	2	0	0
Period 1: Double-blind Phase Death	2	1	0	0
Period 1: Double-blind Phase Lack of Efficacy	1	1	0	0
Period 1: Double-blind Phase Protocol-Specified Criteria for Withdrawal	1	1	0	0
Period 1: Double-blind Phase Randomized but Never Treated	1	1	0	0
Period 1: Double-blind Phase HbsAg Seroconversion	1	0	0	0
Period 1: Double-blind Phase Protocol Violation	0	1	0	0
Period 2: Open-Label TAF Extension Phase Withdrew Consent	0	0	48	22
Period 2: Open-Label TAF Extension Phase Lost to Follow-up	0	0	13	8
Period 2: Open-Label TAF Extension Phase Investigator's Discretion	0	0	9	4
Period 2: Open-Label TAF Extension Phase Protocol-specified Criteria for Withdrawal	0	0	5	4
Period 2: Open-Label TAF Extension Phase Adverse Event	0	0	5	1
Period 2: Open-Label TAF Extension Phase Non-compliance with Study Drug	0	0	4	1
Period 2: Open-Label TAF Extension Phase Pregnancy	0	0	5	0
Period 2: Open-Label TAF Extension Phase Lack of Efficacy	0	0	2	0
Period 2: Open-Label TAF Extension Phase HbsAg Seroconversion	0	0	1	0

Baseline Characteristics

Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Positive for Hepatitis B e Antigen

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAF 25 mg n=581 Participants Double-blind Phase: Tenofovir alafenamide (Vemlidy®; TAF) 25 mg + tenofovir disoproxil fumarate (TDF) placebo tablets administered once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3). Open-label TAF extension Phase: After Week 96 or 144 in the Blinded Treatment Phase, participants were given the option to continue with OL TAF 25 mg for additional 288 or 240 weeks (Up to Week 384), respectively. After the completion of OL TAF Extension Phase treatment or when there was early discontinuation of treatment, participants either switched to commercially available anti-HBV treatments in their country or entered follow-up phase and were followed-up every 4 weeks for 24 weeks off treatment (TFFU) for the assessment of safety.	TDF 300 mg n=292 Participants Double-blind Phase: TDF 300 mg + TAF placebo tablets administered once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3). Open-label TAF extension Phase: After Week 96 or 144 in the Blinded Treatment Phase, participants were given the option to continue with OL TAF 25 mg for additional 288 or 240 weeks (Up to Week 384), respectively. After the completion of OL TAF Extension Phase treatment or when there was early discontinuation of treatment, participants either switched to commercially available anti-HBV treatments in their country or entered follow-up phase and were followed-up every 4 weeks for 24 weeks off treatment (TFFU) for the assessment of safety.	Total n=873 Participants Total of all reporting groups
Age, Continuous	38 Years STANDARD_DEVIATION 11.0 • n=93 Participants	38 Years STANDARD_DEVIATION 11.7 • n=4 Participants	38 Years STANDARD_DEVIATION 11.3 • n=27 Participants
Age, Customized < 50 years	493 Participants n=93 Participants	234 Participants n=4 Participants	727 Participants n=27 Participants
Age, Customized >= 50 years	88 Participants n=93 Participants	58 Participants n=4 Participants	146 Participants n=27 Participants
Sex: Female, Male Female	210 Participants n=93 Participants	103 Participants n=4 Participants	313 Participants n=27 Participants
Sex: Female, Male Male	371 Participants n=93 Participants	189 Participants n=4 Participants	560 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	575 Participants n=93 Participants	290 Participants n=4 Participants	865 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=93 Participants	1 Participants n=4 Participants	5 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	482 Participants n=93 Participants	232 Participants n=4 Participants	714 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants
Race (NIH/OMB) White	96 Participants n=93 Participants	52 Participants n=4 Participants	148 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment Russia	33 Participants n=93 Participants	16 Participants n=4 Participants	49 Participants n=27 Participants
Region of Enrollment Romania	24 Participants n=93 Participants	9 Participants n=4 Participants	33 Participants n=27 Participants
Region of Enrollment Singapore	7 Participants n=93 Participants	2 Participants n=4 Participants	9 Participants n=27 Participants
Region of Enrollment Hong Kong	71 Participants n=93 Participants	50 Participants n=4 Participants	121 Participants n=27 Participants
Region of Enrollment United States	33 Participants n=93 Participants	21 Participants n=4 Participants	54 Participants n=27 Participants
Region of Enrollment Japan	35 Participants n=93 Participants	11 Participants n=4 Participants	46 Participants n=27 Participants
Region of Enrollment United Kingdom	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants
Region of Enrollment India	77 Participants n=93 Participants	33 Participants n=4 Participants	110 Participants n=27 Participants
Region of Enrollment Spain	4 Participants n=93 Participants	0 Participants n=4 Participants	4 Participants n=27 Participants
Region of Enrollment New Zealand	11 Participants n=93 Participants	6 Participants n=4 Participants	17 Participants n=27 Participants
Region of Enrollment Canada	55 Participants n=93 Participants	28 Participants n=4 Participants	83 Participants n=27 Participants
Region of Enrollment Turkey	15 Participants n=93 Participants	11 Participants n=4 Participants	26 Participants n=27 Participants
Region of Enrollment Taiwan	54 Participants n=93 Participants	29 Participants n=4 Participants	83 Participants n=27 Participants
Region of Enrollment South Korea	120 Participants n=93 Participants	53 Participants n=4 Participants	173 Participants n=27 Participants
Region of Enrollment Poland	7 Participants n=93 Participants	5 Participants n=4 Participants	12 Participants n=27 Participants
Region of Enrollment Italy	9 Participants n=93 Participants	5 Participants n=4 Participants	14 Participants n=27 Participants
Region of Enrollment Australia	14 Participants n=93 Participants	6 Participants n=4 Participants	20 Participants n=27 Participants
Region of Enrollment Bulgaria	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Region of Enrollment France	3 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants
HBV DNA	7.6 log10 IU/mL STANDARD_DEVIATION 1.34 • n=93 Participants	7.6 log10 IU/mL STANDARD_DEVIATION 1.41 • n=4 Participants	7.6 log10 IU/mL STANDARD_DEVIATION 1.36 • n=27 Participants
Plasma HBV DNA Level < 8 log10 IU/mL	309 Participants n=93 Participants	150 Participants n=4 Participants	459 Participants n=27 Participants
Plasma HBV DNA Level ≥ 8 log10 IU/mL	272 Participants n=93 Participants	142 Participants n=4 Participants	414 Participants n=27 Participants
IL28B Genotype CC	442 Participants n=93 Participants	210 Participants n=4 Participants	652 Participants n=27 Participants
IL28B Genotype CT	112 Participants n=93 Participants	69 Participants n=4 Participants	181 Participants n=27 Participants
IL28B Genotype TT	23 Participants n=93 Participants	10 Participants n=4 Participants	33 Participants n=27 Participants
IL28B Genotype Missing	4 Participants n=93 Participants	3 Participants n=4 Participants	7 Participants n=27 Participants
Oral Antiviral Treatment Status Treatment Experienced	151 Participants n=93 Participants	77 Participants n=4 Participants	228 Participants n=27 Participants
Oral Antiviral Treatment Status Treatment Naive	430 Participants n=93 Participants	215 Participants n=4 Participants	645 Participants n=27 Participants
Proteinuria by Urinalysis (dipstick) Grade 0	538 Participants n=93 Participants	259 Participants n=4 Participants	797 Participants n=27 Participants
Proteinuria by Urinalysis (dipstick) Grade 1	40 Participants n=93 Participants	31 Participants n=4 Participants	71 Participants n=27 Participants
Proteinuria by Urinalysis (dipstick) Grade 2	3 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants
Proteinuria by Urinalysis (dipstick) Grade 3	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 48

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

Outcome measures

Outcome measures
Measure	TAF 25 mg n=581 Participants TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TDF 300 mg n=292 Participants TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks per amendment 1 \& 2) or 144 weeks (per amendment 3).
Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48	63.9 percentage of participants	66.8 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Serologically Evaluable Full Analysis Set: participants who were randomized, had received at least 1 dose of study drug, and were HBeAg positive and anti-HBe negative or had a value missing value at baseline. Participants were analyzed according to their randomized treatment group. All missing data were treated as no HBeAg seroconversion.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=565 Participants TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TDF 300 mg n=285 Participants TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks per amendment 1 \& 2) or 144 weeks (per amendment 3).
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48	10.3 percentage of participants	8.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: Participants in the Hip Dual-Energy X-ray Absorptiometry (DXA) Analysis Set (participants who were randomized, received at least 1 dose of study drugs, and had nonmissing baseline hip BMD values) with available data were analyzed. Participants were analyzed according to the treatment they actually received. Missing data were excluded from analysis.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=537 Participants TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TDF 300 mg n=271 Participants TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks per amendment 1 \& 2) or 144 weeks (per amendment 3).
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	-0.100 percentage change Standard Deviation 2.2912	-1.715 percentage change Standard Deviation 2.5723

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: Participants in the Spine DXA Analysis Set (participants who were randomized, received at least 1 dose of study drugs, and had nonmissing baseline spine BMD values) with available data were analyzed. Participants were analyzed according to the treatment they actually received. Missing data were excluded from analysis.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=543 Participants TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TDF 300 mg n=274 Participants TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks per amendment 1 \& 2) or 144 weeks (per amendment 3).
Percent Change From Baseline in Spine BMD at Week 48	-0.417 percentage change Standard Deviation 2.9343	-2.294 percentage change Standard Deviation 3.1331

SECONDARY outcome

Timeframe: Baseline, Week 48

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

Outcome measures

Outcome measures
Measure	TAF 25 mg n=553 Participants TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TDF 300 mg n=283 Participants TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks per amendment 1 \& 2) or 144 weeks (per amendment 3).
Change From Baseline at Week 48 in Serum Creatinine	0.009 mg/dL Standard Deviation 0.1238	0.026 mg/dL Standard Deviation 0.0948

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 48 weeks

Population: Participants in the Safety Analysis Set with at least 1 postbaseline urine protein value were analyzed.

Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method.

Outcome measures

Outcome measures
Measure	TAF 25 mg n=577 Participants TAF 25 mg tablet + TDF placebo tablet once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	TDF 300 mg n=286 Participants TDF 300 mg tablet + TAF placebo tablet once daily for up to 96 weeks per amendment 1 \& 2) or 144 weeks (per amendment 3).
Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48 Grade 1	23.9 percentage of participants	17.8 percentage of participants
Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48 Grade 2	3.5 percentage of participants	4.5 percentage of participants
Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48 Grade 3	0 percentage of participants	0.3 percentage of participants

Adverse Events

Double-blind Phase: TAF 25 mg

Serious events: 44 serious events

Other events: 290 other events

Deaths: 2 deaths

Double-blind Phase: TDF 300 mg

Serious events: 20 serious events

Other events: 143 other events

Deaths: 1 deaths

Open-label TAF Extension Phase: TAF 25 mg to TAF 25 mg

Serious events: 59 serious events

Other events: 168 other events

Deaths: 0 deaths

Open-label TAF Extension Phase: TDF 300 mg to TAF 25 mg

Serious events: 32 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Double-blind Phase: TAF 25 mg n=581 participants at risk TAF 25 mg + TDF placebo tablets administered once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	Double-blind Phase: TDF 300 mg n=292 participants at risk TDF 300 mg + TAF placebo tablets administered once daily for up to 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).	Open-label TAF Extension Phase: TAF 25 mg to TAF 25 mg n=514 participants at risk After Week 96 or 144 in the Blinded Treatment Phase, participants were given the option to continue with OL TAF 25 mg for additional 288 or 240 weeks (Up to Week 384). After the completion of OL TAF Extension Phase treatment or when there was early discontinuation of treatment, participants either switched to commercially available anti-HBV treatments in their country or entered follow-up phase and were followed-up every 4 weeks for 24 weeks off treatment (TFFU) for the assessment of safety.	Open-label TAF Extension Phase: TDF 300 mg to TAF 25 mg n=253 participants at risk After Week 96 or 144 in the Blinded Treatment Phase, participants were given the option to switch to Open-label (OL) TAF 25 mg for additional 288 or 240 weeks (Up to Week 384). After the completion of OL TAF Extension Phase treatment or when there was early discontinuation of treatment, participants either switched to commercially available anti-HBV treatments in their country or entered follow-up phase and were followed-up every 4 weeks for 24 weeks off treatment (TFFU) for the assessment of safety.
Gastrointestinal disorders Diarrhoea	6.0% 35/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	6.5% 19/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	2.5% 13/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	2.4% 6/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Gastrointestinal disorders Dyspepsia	5.5% 32/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	5.5% 16/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	3.1% 16/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	3.6% 9/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.3% 19/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	3.4% 10/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	3.3% 17/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	5.1% 13/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Gastrointestinal disorders Nausea	6.0% 35/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	5.1% 15/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	0.97% 5/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	0.79% 2/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
General disorders Fatigue	6.2% 36/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	4.8% 14/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	1.2% 6/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	2.0% 5/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Infections and infestations Nasopharyngitis	12.2% 71/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	9.9% 29/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	6.4% 33/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	5.1% 13/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Infections and infestations Upper respiratory tract infection	12.0% 70/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	11.3% 33/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	6.2% 32/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	6.7% 17/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 39/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	7.5% 22/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	4.7% 24/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	5.9% 15/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Musculoskeletal and connective tissue disorders Back pain	6.2% 36/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	7.5% 22/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	3.9% 20/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	4.7% 12/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Nervous system disorders Headache	10.2% 59/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	10.3% 30/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	6.2% 32/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	7.9% 20/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 48/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	8.2% 24/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	2.9% 15/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	7.5% 19/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.
Vascular disorders Hypertension	2.4% 14/581 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	2.1% 6/292 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	4.1% 21/514 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.	5.9% 15/253 • All-Cause Mortality: Randomization up to approximately 416 weeks; Adverse Events: First dose date up to Week 384 All-cause mortality: Randomized Analysis Set: All participants randomized into the study. Adverse events: Safety Analysis Set: Participants who received at least 1 dose of study drug in the respective period.

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