Chronic Hepatitis B
Conditions
Keywords
stopping oral antiviral therapy, HBsAg loss, seroconversion, restarting oral antiviral therapy
Brief summary
The primary objective of this study is to evaluate hepatitis B surface antigen (HBsAg) loss and seroconversion in participants who stop tenofovir disoproxil fumarate (TDF) (Stop TDF arm) compared to participants who continue TDF (Continue TDF arm). Only participants who already are on treatment with TDF monotherapy or TDF in combination with lamivudine or emtricitabine for at least 4 years and who achieved and maintained virologic suppression (\< 400 copies/mL) for 3.5 or more years will be included in this study. One treatment arm will stop the TDF therapy while the other treatment arm will continue the TDF therapy. Participants in the Stop TDF arm will be monitored very closely with special focus on biochemical flares (especially alanine aminotransferase (ALT) increases) and virological relapses (Hepatitis B viral load increases). If any participant in the Stop TDF arm exceeds one or more predefined limits for such flares or relapses, TDF treatment will be reinstituted.
Interventions
DRUGTDF
Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily
OTHERStop TDF
Participants will stop TDF therapy
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Chronic hepatitis B, hepatitis B e-antigen negative, hepatitis B e-antibody positive, and hepatitis B surface antigen-positive * Hepatitis B e Antigen (HBeAg)-negative at the beginning of TDF therapy (i.e. TDF monotherapy or combination of TDF + lamivudine or TDF + emtricitabine) * Received continuous TDF therapy (i.e. TDF monotherapy or combination of TDF + lamivudine or TDF + emtricitabine) treatment for at least 4 years prior to screening. If TDF has been used in combination with lamivudine or emtricitabine, lamivudine or emtricitabine must have been stopped at least 12 weeks prior to screening * Documented hepatitis B virus DNA (HBV DNA) \< 400 copies/mL for at least 3.5 years prior to screening and at screening * ALT within normal range * α-fetoprotein (AFP) \<= 50 ng/mL * Calculated creatinine clearance \>= 70 mL/min by Cockcroft-Gault formula using ideal body weight * \<= 10 kPa on Fibroscan assessment * A negative serum pregnancy test for female subjects * Adult subjects \>= 18 years of age Key
Exclusion criteria
* Known cirrhosis * Evidence of fibrosis \>= Stage 3 (METAVIR) on liver biopsy or Fibroscan \> 10 kPa within 6 months prior to screening * Documentation of confirmed episodes (i.e., 2 consecutive values) of HBV DNA \> 400 copies/mL within 3.5 years prior to screening * History of decompensated liver disease (defined as direct \[conjugated\] bilirubin \> 1.5 x upper limit of normal, prothrombin time (PT) \> 1.5 x upper limit of normal, platelets \< 75,000/mm³, serum albumin \< 3.0 g/dL * History of clinical hepatic decompensation in the judgement of the investigator * Evidence of hepatocellular carcinoma * Significant bone disease (in the judgment of the investigator) * Serological evidence of coinfection with human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis D infection * Known hypersensitivity to TDF, its metabolites, or formulation excipients * Concomitant therapy with disallowed medications * History of malignant disease * Lactating females * Females wishing to became pregnant during the duration of the stud * Subjects participating in another clinical trial can only be enrolled at the discretion of the Medical Monitor Note: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms | Week 144 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Baseline to Week 144 | * 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. |
| Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm | Weeks 48, 96, and 144 | — |
| Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144 | Weeks 96 and 144 | 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. |
| Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) | Baseline to Week 144 | — |
| Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms | Week 96 | 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. |
| Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Baseline to Week 144 | Viral suppression is defined as 2 consecutive assessments of HBV DNA \< 400 copies/mL (69 IU/mL) through Week 144. |
Countries
Germany
Participant flow
Recruitment details
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.
Pre-assignment details
65 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Stop TDF Participants stopped tenofovir disoproxil fumarate (Viread®; TDF) monotherapy at baseline. | 21 |
| Continue TDF Participants continued TDF monotherapy 300 mg once daily. | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Randomized but not Treated | 0 | 1 |
Baseline characteristics
| Characteristic | Stop TDF | Continue TDF | Total |
|---|---|---|---|
| Age, Continuous | 44.6 years STANDARD_DEVIATION 10.51 | 45.0 years STANDARD_DEVIATION 7.06 | 44.8 years STANDARD_DEVIATION 8.85 |
| Hepatitis B Virus Surface Antigen | 4.4 log10 IU/mL STANDARD_DEVIATION 0.71 | 4.5 log10 IU/mL STANDARD_DEVIATION 0.35 | 4.5 log10 IU/mL STANDARD_DEVIATION 0.56 |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 19 Participants | 37 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 18 Participants | 15 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 8 | 0 / 21 |
| other Total, other adverse events | 17 / 21 | 6 / 8 | 16 / 21 |
| serious Total, serious adverse events | 4 / 21 | 1 / 8 | 3 / 21 |
Outcome results
Primary
Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stop TDF | Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms | 0.236 Proportion of participants |
| Continue TDF | Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms | 0 Proportion of participants |
p-value: 0.022Log Rank
Secondary
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms
* 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 0.5 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 1.53 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 0.17 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 84 | -0.69 log10 IU/mL | Standard Deviation 1.084 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 12 | -0.03 log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 16 | -0.73 log10 IU/mL | Standard Deviation 0.438 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 20 | -0.42 log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 24 | -1.41 log10 IU/mL | Standard Deviation 1.211 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 28 | -0.88 log10 IU/mL | Standard Deviation 0.916 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 32 | -0.96 log10 IU/mL | Standard Deviation 1.211 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 36 | -0.26 log10 IU/mL | Standard Deviation 0.461 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 40 | -0.97 log10 IU/mL | Standard Deviation 1.275 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 44 | -0.59 log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 48 | -1.01 log10 IU/mL | Standard Deviation 1.295 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 60 | -1.03 log10 IU/mL | Standard Deviation 1.236 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 72 | -0.64 log10 IU/mL | Standard Deviation 1.085 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 96 | -0.69 log10 IU/mL | Standard Deviation 1.031 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 108 | -0.69 log10 IU/mL | Standard Deviation 1.088 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 120 | -0.58 log10 IU/mL | Standard Deviation 0.87 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 132 | -0.52 log10 IU/mL | Standard Deviation 0.941 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 144 | -0.51 log10 IU/mL | Standard Deviation 0.861 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 120 | -0.20 log10 IU/mL | Standard Deviation 0.136 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 60 | -0.10 log10 IU/mL | Standard Deviation 0.133 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 20 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 4 | -0.01 log10 IU/mL | Standard Deviation 0.105 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 72 | -0.14 log10 IU/mL | Standard Deviation 0.142 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 16 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 12 | -0.02 log10 IU/mL | Standard Deviation 0.137 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 84 | -0.16 log10 IU/mL | Standard Deviation 0.164 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 10 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 144 | -0.22 log10 IU/mL | Standard Deviation 0.16 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 96 | -0.17 log10 IU/mL | Standard Deviation 0.159 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 8 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 132 | -0.22 log10 IU/mL | Standard Deviation 0.172 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 36 | -0.08 log10 IU/mL | Standard Deviation 0.14 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 108 | -0.17 log10 IU/mL | Standard Deviation 0.145 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 40 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 32 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 6 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 44 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 28 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 2 | NA log10 IU/mL | — |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 48 | -0.11 log10 IU/mL | Standard Deviation 0.101 |
| Continue TDF | Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms | Change from Baseline at Week 24 | -0.07 log10 IU/mL | Standard Deviation 0.139 |
Secondary
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF)
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 28.6 Percentage of participants |
| Continue TDF | 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 | 100.0 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 100.0 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 100.0 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 50.0 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 33.3 Percentage of participants |
| Continue TDF | 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 | 14.3 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 40 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
| Continue TDF | 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 | 0 Percentage of participants |
Secondary
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups)
Viral suppression is defined as 2 consecutive assessments of HBV DNA \< 400 copies/mL (69 IU/mL) through Week 144.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week12 | 21.1 Percentage of participants |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Stop TDF | 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 |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 96 | 100.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week12 | 0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 48 | 100.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 16 | 0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 144 | 87.5 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 20 | 0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 60 | 100.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 24 | 0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 108 | 100.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 28 | 0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 72 | 60.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 32 | 66.7 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 132 | 100.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 36 | 100.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 84 | 100.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 40 | 100.0 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 120 | 71.4 Percentage of participants |
| Continue TDF | Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) | Week 44 | 100.0 Percentage of participants |
Secondary
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stop TDF | Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm | TDF Restart at Week 48 | 0.143 Proportion of participants |
| Stop TDF | Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm | TDF Restart at Week 96 | 0.238 Proportion of participants |
| Stop TDF | Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm | TDF Restart at Week 144 | 0.381 Proportion of participants |
Secondary
Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms
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.
Time frame: Week 96
Population: HBsAg Loss and Seroconversion Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stop TDF | Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms | 0.172 Proportion of participants |
| Continue TDF | Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms | 0 Proportion of participants |
Secondary
Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stop TDF | 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 |
| Stop TDF | 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 |
| Continue TDF | Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144 | HBsAg Seroconversion at Week 96 | 0 Proportion of participants |
| Continue TDF | Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144 | HBsAg Seroconversion at Week 144 | 0 Proportion of participants |