Trial Outcomes & Findings for Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB (NCT NCT01320943)

NCT ID: NCT01320943

Last Updated: 2017-08-29

Results Overview

HBsAg loss is defined as qualitative HBsAg result changing from positive at baseline (BL) to negative at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

43 participants

Primary outcome timeframe

Week 144

Results posted on

2017-08-29

Participant Flow

Participants were enrolled at 13 study sites in Germany. The first participant was screened on 26 April 2011. The last study visit occurred on 23 August 2016.

65 participants were screened.

Participant milestones

Participant milestones
Measure	Stop TDF Participants stopped tenofovir disoproxil fumarate (Viread®; TDF) monotherapy at baseline.	Continue TDF Participants continued TDF monotherapy 300 mg once daily.
Overall Study STARTED	21	22
Overall Study COMPLETED	20	20
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Stop TDF Participants stopped tenofovir disoproxil fumarate (Viread®; TDF) monotherapy at baseline.	Continue TDF Participants continued TDF monotherapy 300 mg once daily.
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	0	1
Overall Study Randomized but not Treated	0	1

Baseline Characteristics

Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stop TDF n=21 Participants Participants stopped tenofovir disoproxil fumarate (Viread®; TDF) monotherapy at baseline.	Continue TDF n=21 Participants Participants continued TDF monotherapy 300 mg once daily.	Total n=42 Participants Total of all reporting groups
Age, Continuous	44.6 years STANDARD_DEVIATION 10.51 • n=5 Participants	45.0 years STANDARD_DEVIATION 7.06 • n=7 Participants	44.8 years STANDARD_DEVIATION 8.85 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Hepatitis B Virus Surface Antigen	4.4 log10 IU/mL STANDARD_DEVIATION 0.71 • n=5 Participants	4.5 log10 IU/mL STANDARD_DEVIATION 0.35 • n=7 Participants	4.5 log10 IU/mL STANDARD_DEVIATION 0.56 • n=5 Participants

PRIMARY outcome

Timeframe: Week 144

Population: HBsAg Loss and Seroconversion Full Analysis Set: participants in the Full Analysis Set who had at least one post-baseline HBsAg value and with HBsAg positive and HBsAb negative or missing at baseline.

HBsAg loss is defined as qualitative HBsAg result changing from positive at baseline (BL) to negative at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Stop TDF n=21 Participants Participants stopped tenofovir disoproxil fumarate monotherapy at baseline.	Continue TDF n=21 Participants Participants continued TDF monotherapy 300 mg once daily.	Continue TDF Participants who continued TDF monotherapy 300 mg once daily.
Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms	0.236 Proportion of participants Interval 0.095 to 0.516	0 Proportion of participants No participants in the Continue TDF group had HBsAg loss.	—

SECONDARY outcome

Timeframe: Weeks 96 and 144

Population: HBsAg Loss and Seroconversion Full Analysis Set: participants in the Full Analysis Set who had at least 1 post-baseline HBsAg value and with HBsAg positive and HBsAb negative or missing at baseline.

HBsAg seroconversion is defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit. Proportions are based on the Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Stop TDF n=21 Participants Participants stopped tenofovir disoproxil fumarate monotherapy at baseline.	Continue TDF n=21 Participants Participants continued TDF monotherapy 300 mg once daily.	Continue TDF Participants who continued TDF monotherapy 300 mg once daily.
Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144 HBsAg Seroconversion at Week 96	0.056 Proportion of participants Interval 0.008 to 0.334	0 Proportion of participants No participants in the Continue TDF arm achieved HBsAg seroconversion at Week 96	—
Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144 HBsAg Seroconversion at Week 144	0.203 Proportion of participants Interval 0.069 to 0.513	0 Proportion of participants No participants in the Continue TDF arm achieved HBsAg seroconversion at Week 144	—

SECONDARY outcome

Timeframe: Baseline to Week 144

Population: Participants in the Full Analysis Set ( participants who were randomized to Stop TDF arm and had a baseline visit or who were randomized to Continue TDF arm and received at least 1 dose of study drug) with available data were analyzed.

* The analyses were summarized by 3 treatment subgroups: Stop TDF (TDF-Free), Restart TDF, and Continue TDF * When participant randomized in the Stop TDF group restarted TDF therapy, that participant was considered part of the Restart TDF group from that point forward. For Restart TDF group, baseline is defined as the last available record on or prior to the restart date of TDF.

Outcome measures

Outcome measures
Measure	Stop TDF n=21 Participants Participants stopped tenofovir disoproxil fumarate monotherapy at baseline.	Continue TDF n=8 Participants Participants continued TDF monotherapy 300 mg once daily.	Continue TDF n=21 Participants Participants who continued TDF monotherapy 300 mg once daily.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 2	-0.03 log10 IU/mL Standard Deviation 0.139	—	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 2.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 4	-0.03 log10 IU/mL Standard Deviation 0.170	—	-0.01 log10 IU/mL Standard Deviation 0.105
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 6	-0.02 log10 IU/mL Standard Deviation 0.192	—	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 6.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 8	0.04 log10 IU/mL Standard Deviation 0.500	—	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 8.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 10	0.01 log10 IU/mL Standard Deviation 0.556	—	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 10.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 12	-0.11 log10 IU/mL Standard Deviation 0.621	-0.03 log10 IU/mL	-0.02 log10 IU/mL Standard Deviation 0.137
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 16	-0.35 log10 IU/mL Standard Deviation 0.741	-0.73 log10 IU/mL Standard Deviation 0.438	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 16.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 20	-0.48 log10 IU/mL Standard Deviation 0.949	-0.42 log10 IU/mL	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 20.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 24	-0.56 log10 IU/mL Standard Deviation 1.029	-1.41 log10 IU/mL Standard Deviation 1.211	-0.07 log10 IU/mL Standard Deviation 0.139
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 28	-0.60 log10 IU/mL Standard Deviation 0.969	-0.88 log10 IU/mL Standard Deviation 0.916	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 28.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 32	-0.77 log10 IU/mL Standard Deviation 1.126	-0.96 log10 IU/mL Standard Deviation 1.211	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 32.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 36	-0.67 log10 IU/mL Standard Deviation 1.151	-0.26 log10 IU/mL Standard Deviation 0.461	-0.08 log10 IU/mL Standard Deviation 0.140
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 40	-0.78 log10 IU/mL Standard Deviation 1.198	-0.97 log10 IU/mL Standard Deviation 1.275	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 40.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 44	-0.87 log10 IU/mL Standard Deviation 1.238	-0.59 log10 IU/mL	NA log10 IU/mL Standard Deviation NA HBsAg assessment in the Continue TDF arm was not performed at Week 44.
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 48	-0.88 log10 IU/mL Standard Deviation 1.314	-1.01 log10 IU/mL Standard Deviation 1.295	-0.11 log10 IU/mL Standard Deviation 0.101
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 60	-0.96 log10 IU/mL Standard Deviation 1.353	-1.03 log10 IU/mL Standard Deviation 1.236	-0.10 log10 IU/mL Standard Deviation 0.133
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 72	-1.22 log10 IU/mL Standard Deviation 1.478	-0.64 log10 IU/mL Standard Deviation 1.085	-0.14 log10 IU/mL Standard Deviation 0.142
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 84	-1.21 log10 IU/mL Standard Deviation 1.555	-0.69 log10 IU/mL Standard Deviation 1.084	-0.16 log10 IU/mL Standard Deviation 0.164
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 96	-1.22 log10 IU/mL Standard Deviation 1.530	-0.69 log10 IU/mL Standard Deviation 1.031	-0.17 log10 IU/mL Standard Deviation 0.159
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 108	-1.43 log10 IU/mL Standard Deviation 1.573	-0.69 log10 IU/mL Standard Deviation 1.088	-0.17 log10 IU/mL Standard Deviation 0.145
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 120	-1.56 log10 IU/mL Standard Deviation 1.752	-0.58 log10 IU/mL Standard Deviation 0.870	-0.20 log10 IU/mL Standard Deviation 0.136
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 132	-1.74 log10 IU/mL Standard Deviation 1.829	-0.52 log10 IU/mL Standard Deviation 0.941	-0.22 log10 IU/mL Standard Deviation 0.172
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms Change from Baseline at Week 144	-1.80 log10 IU/mL Standard Deviation 1.796	-0.51 log10 IU/mL Standard Deviation 0.861	-0.22 log10 IU/mL Standard Deviation 0.160

SECONDARY outcome

Timeframe: Weeks 48, 96, and 144

Population: Full Analysis Set (FAS): participants who were randomized to Stop TDF group and had a baseline visit or who were randomized to Continue TDF group and received at least 1 dose of study drug. Proportions are based on the Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Stop TDF n=21 Participants Participants stopped tenofovir disoproxil fumarate monotherapy at baseline.	Continue TDF Participants continued TDF monotherapy 300 mg once daily.	Continue TDF Participants who continued TDF monotherapy 300 mg once daily.
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm TDF Restart at Week 48	0.143 Proportion of participants Interval 0.048 to 0.38	—	—
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm TDF Restart at Week 96	0.238 Proportion of participants Interval 0.107 to 0.481	—	—
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm TDF Restart at Week 144	0.381 Proportion of participants Interval 0.212 to 0.619	—	—

SECONDARY outcome

Timeframe: Baseline to Week 144

Population: Participants in the FAS with available data were analyzed. When participant randomized in the Stop TDF group restarted TDF therapy, that participant was considered part of the Restart TDF group from that point forward. 1 participant restarted TDF during Wk 72, thus was reported in both Stop TDF and Restart TDF arms based on the TDF restart date.

Viral suppression is defined as 2 consecutive assessments of HBV DNA \< 400 copies/mL (69 IU/mL) through Week 144.

Outcome measures

Outcome measures
Measure	Stop TDF n=21 Participants Participants stopped tenofovir disoproxil fumarate monotherapy at baseline.	Continue TDF n=8 Participants Participants continued TDF monotherapy 300 mg once daily.	Continue TDF Participants who continued TDF monotherapy 300 mg once daily.
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 2	52.4 Percentage of participants	—	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 4	5.3 Percentage of participants	—	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 6	10.0 Percentage of participants	—	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 8	5.0 Percentage of participants	—	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 10	15.0 Percentage of participants	—	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week12	21.1 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 16	31.6 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 20	27.8 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 24	16.7 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 28	17.6 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 32	12.5 Percentage of participants	66.7 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 36	29.4 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 40	22.2 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 44	29.4 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 48	27.8 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 60	33.3 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 72	35.3 Percentage of participants	60.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 84	31.3 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 96	37.5 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 108	37.5 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 120	40.0 Percentage of participants	71.4 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 132	38.5 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) Week 144	46.2 Percentage of participants	87.5 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Week 144

Population: Participants in the Full Analysis Set with available data were analyzed. Percentages are based on the number of participants with non-missing laboratory test results at each visit. One participant restarted TDF during Weeks 72 and 120 and thus was reported in both the Stop TDF and Re-Start TDF groups based on the date of TDF restart.

Outcome measures

Outcome measures
Measure	Stop TDF n=21 Participants Participants stopped tenofovir disoproxil fumarate monotherapy at baseline.	Continue TDF n=8 Participants Participants continued TDF monotherapy 300 mg once daily.	Continue TDF Participants who continued TDF monotherapy 300 mg once daily.
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 2	4.8 Percentage of participants	—	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 4	0 Percentage of participants	—	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 6	35.0 Percentage of participants	—	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 8	60.0 Percentage of participants	—	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 10	70.0 Percentage of participants	—	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 12	42.1 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 16	26.3 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 20	11.8 Percentage of participants	100.0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 24	16.7 Percentage of participants	50.0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 28	11.8 Percentage of participants	33.3 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 32	13.3 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 36	11.8 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 40	23.5 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 44	11.8 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 48	16.7 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 60	22.2 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 72	11.8 Percentage of participants	40 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 84	18.8 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 96	12.5 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 108	18.8 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 120	20.0 Percentage of participants	14.3 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 132	0 Percentage of participants	28.6 Percentage of participants	—
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) Week 144	15.4 Percentage of participants	0 Percentage of participants	—

SECONDARY outcome

Timeframe: Week 96

Population: HBsAg Loss and Seroconversion Full Analysis Set

HBsAg loss is defined as qualitative HBsAg result changing from positive at baseline (BL) to negative at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Stop TDF n=21 Participants Participants stopped tenofovir disoproxil fumarate monotherapy at baseline.	Continue TDF n=21 Participants Participants continued TDF monotherapy 300 mg once daily.	Continue TDF Participants who continued TDF monotherapy 300 mg once daily.
Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms	0.172 Proportion of participants Interval 0.058 to 0.446	0 Proportion of participants No participants in the Continue TDF group had HBsAg loss	—

Adverse Events

Stop TDF (TDF-Free) [Termination Emergent]

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Re-start TDF [TDF Emergent]

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Continue TDF [TDF Emergent]

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Stop TDF (TDF-Free) [Termination Emergent] n=21 participants at risk Participants stopped TDF monotherapy at baseline.	Re-start TDF [TDF Emergent] n=8 participants at risk Stop TDF participants who restarted TDF therapy.	Continue TDF [TDF Emergent] n=21 participants at risk Participants continued TDF monotherapy 300 mg once daily.
Cardiac disorders Acute coronary syndrome	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/8 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	4.8% 1/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF
General disorders Surgical failure	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	12.5% 1/8 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF
Hepatobiliary disorders Cholelithiasis	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/8 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	4.8% 1/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF
Infections and infestations Appendicitis	4.8% 1/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/8 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/8 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	4.8% 1/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF
Injury, poisoning and procedural complications Limb traumatic amputation	4.8% 1/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/8 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF
Investigations Alanine aminotransferase increased	9.5% 2/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/8 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF
Psychiatric disorders Depression	0.00% 0/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	0.00% 0/8 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF	4.8% 1/21 • Up to 144 weeks * Safety Analysis Set * TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group * Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences

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