A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B

A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of HBeAg Positive Chronic Hepatitis B

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00116805

Enrollment

266

Registered

2005-07-01

Start date

2005-06-30

Completion date

2016-01-31

Last updated

2017-03-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis B

Keywords

tenofovir, adefovir, hepatitis B, HBeAg Positive

Brief summary

The primary objectives of this study are to compare the efficacy, safety, and tolerability of tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) for the treatment of HBeAg-positive chronic hepatitis B. Participants will receive TDF or ADV for 48 weeks (double-blind). After 48 weeks, eligible participants switched to open-label TDF for up to 480 weeks.

Interventions

DRUGTDF

300 mg tablet administered orally once daily

DRUGADV

10 mg tablet administered orally once daily

DRUGTDF placebo

Tablet administered orally once daily

DRUGADV placebo

Tablet administered orally once daily

DRUGFTC/TDF

200/300 mg fixed-dose combination (FDC) tablet administered orally once daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 69 Years

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: A patient must meet all of the following inclusion criteria to be eligible for participation in this study: * Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for more than 6 months * 18 through 69 years of age, inclusive * Active hepatitis B e-antigen (HBeAg) positive chronic HBV infection, with all of the following: * HBeAg positive at screening * Alanine aminotransferase (ALT) levels \> 2 × ULN and ≤ 10 × the upper limit of the normal range (ULN) * Serum HBV DNA \> 1 million copies/mL at screening * creatinine clearance ≥ 70 mL/min * hemoglobin ≥ 8 g/dL * neutrophils ≥ 1,000 /mL * Knodell necroinflammatory score ≥ 3 and a Knodell fibrosis score \< 4; however, up to 96 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible for enrollment * Negative serum β-human chorionic gonadotropin (hCG) * Nucleotide naïve, ie, no prior nucleotide (TDF or ADV) therapy for \> 12 weeks * Nucleoside naïve, ie, no prior nucleoside (any nucleoside) therapy for \> 12 weeks * Willing and able to provide written informed consent * Liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline Key

Exclusion criteria

A patient who meets any of the following

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48	Baseline; Week 48	Complete response was a composite endpoint defined as histological response and HBV DNA \< 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.

Secondary

Measure	Time frame	Description
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96	Week 96	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Weeks 144, 192, 240, 288, 336, and 384	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480	Weeks 432 and 480	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	—
Percentage of Participants With Histological Response at Week 48	Baseline; Week 48	Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
Percentage of Participants With Histological Response at Week 240	Baseline; Week 240	Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48	Baseline; Week 48	The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240	Baseline; Week 240	The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).
Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Baseline; Week 48	Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.
Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Baseline; Week 240	Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48	Baseline; Week 48	ALT normalization was defined as ALT \> upper limit of normal (ULN) at baseline and within the normal range at the end of blinded treatment. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Percentage of Participants With ALT Normalization at Week 96	Baseline; Week 96	ALT normalization was defined as ALT \> ULN at baseline and within the normal range at Week 96. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Baseline; Weeks 144, 192, 240, 288, 336, and 384	ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Percentage of Participants With ALT Normalization at Weeks 432 and 480	Baseline; Weeks 432 and 480	ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48	Week 48	—
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48	Baseline; Week 48	HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 48. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 48.
Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96	Baseline; Week 96	HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 96. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 96.
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48	Baseline; Week 48	HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 48. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 48.
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96	Baseline; Week 96	HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Baseline; Week 48	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA ≥ 400 copies/mL.
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Baseline; Weeks 49 to 96	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 96 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 48 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Baseline; Weeks 97 to 144	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 144 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 96 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 96 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Baseline; Weeks 145 to 192	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 192 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 144 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 144 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Baseline; Weeks 193 to 240	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 240 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 192 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 192 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Baseline; Weeks 241 to 288	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 288 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 240 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 240 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Baseline; Weeks 289 to 336	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 336 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 288 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 288 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Baseline; Weeks 337 to 384	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 384 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 336 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 336 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Baseline; Weeks 385 to 432	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Baseline; Weeks 433 to 480	Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	—

Countries

Australia, Bulgaria, Canada, Czechia, France, Germany, Greece, Italy, Netherlands, New Zealand, Poland, Spain, Turkey (Türkiye), United Kingdom, United States

Participant flow

Recruitment details

Participants were enrolled at study sites in North America, Europe, and Australia/New Zealand. The first participant was screened on 09 June 2005. The last study visit occurred on 28 January 2016.

Pre-assignment details

603 participants were screened.

Participants by arm

Arm	Count
TDF-TDF TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	176
ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	90
Total	266

Withdrawals & dropouts

Period	Reason	FG000	FG001
Double-blind Period Through Week 48	Lost to Follow-up	6	2
Double-blind Period Through Week 48	Protocol Violation	1	1
Double-blind Period Through Week 48	Withdrew Consent	4	2
Open-label Period Weeks 145 - 192	Completed Study	1	1
Open-label Period Weeks 145 - 192	Investigator's Discretion	2	0
Open-label Period Weeks 145 - 192	Lost to Follow-up	3	1
Open-label Period Weeks 145 - 192	Protocol Violation	1	0
Open-label Period Weeks 145 - 192	Safety, Tolerability, or Efficacy Reason	0	1
Open-label Period Weeks 145 - 192	Seroconversion	0	1
Open-label Period Weeks 145 - 192	Withdrew Consent	3	2
Open-label Period Weeks 193 - 240	Completed Study	0	1
Open-label Period Weeks 193 - 240	Investigator's Discretion	1	0
Open-label Period Weeks 193 - 240	Lost to Follow-up	3	0
Open-label Period Weeks 193 - 240	Safety, Tolerability, or Efficacy Reason	2	2
Open-label Period Weeks 193 - 240	Withdrew Consent	7	1
Open-label Period Weeks 241 - 288	Safety, Tolerability, or Efficacy Reason	2	0
Open-label Period Weeks 241 - 288	Withdrew Consent	4	0
Open-label Period Weeks 289 - 336	Completed Study	0	1
Open-label Period Weeks 289 - 336	Investigator's Discretion	3	2
Open-label Period Weeks 289 - 336	Lost to Follow-up	1	1
Open-label Period Weeks 289 - 336	Protocol Violation	0	1
Open-label Period Weeks 289 - 336	Safety, Tolerability, or Efficacy Reason	0	1
Open-label Period Weeks 289 - 336	Study Site Discontinued	0	1
Open-label Period Weeks 289 - 336	Withdrew Consent	2	0
Open-label Period Weeks 337 - 384	Completed Study	1	0
Open-label Period Weeks 337 - 384	Investigator's Discretion	1	0
Open-label Period Weeks 337 - 384	Lost to Follow-up	2	0
Open-label Period Weeks 337 - 384	Protocol Violation	1	0
Open-label Period Weeks 337 - 384	Withdrew Consent	3	1
Open-label Period Weeks 385 - 432	Investigator's Discretion	1	0
Open-label Period Weeks 385 - 432	Withdrew Consent	1	0
Open-label Period Weeks 433 - 480	Investigator's Discretion	1	0
Open-label Period Weeks 433 - 480	Withdrew Consent	3	0
Open-label Period Weeks 49 - 96	Investigator's Discretion	1	0
Open-label Period Weeks 49 - 96	Lost to Follow-up	2	0
Open-label Period Weeks 49 - 96	Protocol Violation	2	0
Open-label Period Weeks 49 - 96	Safety, Tolerability, or Efficacy Reason	1	0
Open-label Period Weeks 49 - 96	Seroconversion	2	0
Open-label Period Weeks 49 - 96	Withdrew Consent	2	1
Open-label Period Weeks 97 - 144	Completed Study	1	0
Open-label Period Weeks 97 - 144	Investigator's Discretion	2	0
Open-label Period Weeks 97 - 144	Lost to Follow-up	5	2
Open-label Period Weeks 97 - 144	Protocol Violation	0	1
Open-label Period Weeks 97 - 144	Seroconversion	2	3
Open-label Period Weeks 97 - 144	Withdrew Consent	1	3

Baseline characteristics

Characteristic	TDF-TDF	ADV-TDF	Total
Age, Categorical <=18 years	3 Participants	1 Participants	4 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	173 Participants	89 Participants	262 Participants
Age, Continuous	34 years STANDARD_DEVIATION 11.3	34 years STANDARD_DEVIATION 12.2	34 years STANDARD_DEVIATION 11.6
Baseline Alanine Aminotransferase (ALT) above the Upper Limit of the Normal (ULN) Range No	7 participants	0 participants	7 participants
Baseline Alanine Aminotransferase (ALT) above the Upper Limit of the Normal (ULN) Range Yes	169 participants	90 participants	259 participants
Baseline Hepatitis B Deoxyribonucleic Acid (HBV DNA)	8.64 log10 copies/mL STANDARD_DEVIATION 1.076	8.88 log10 copies/mL STANDARD_DEVIATION 0.93	8.72 log10 copies/mL STANDARD_DEVIATION 1.033
Baseline Knodell Necroinflammatory Score	8.3 units on a scale STANDARD_DEVIATION 2.11	8.5 units on a scale STANDARD_DEVIATION 2.07	8.4 units on a scale STANDARD_DEVIATION 2.09
Prior Lamivudine or FTC Treatment No	168 participants	89 participants	257 participants
Prior Lamivudine or FTC Treatment Yes	8 participants	1 participants	9 participants
Region of Enrollment Australia	22 participants	6 participants	28 participants
Region of Enrollment Bulgaria	17 participants	11 participants	28 participants
Region of Enrollment Canada	17 participants	10 participants	27 participants
Region of Enrollment Czech Republic	3 participants	5 participants	8 participants
Region of Enrollment France	11 participants	3 participants	14 participants
Region of Enrollment Germany	20 participants	8 participants	28 participants
Region of Enrollment Greece	1 participants	2 participants	3 participants
Region of Enrollment Italy	0 participants	1 participants	1 participants
Region of Enrollment Netherlands	6 participants	4 participants	10 participants
Region of Enrollment New Zealand	10 participants	11 participants	21 participants
Region of Enrollment Poland	16 participants	8 participants	24 participants
Region of Enrollment Spain	7 participants	2 participants	9 participants
Region of Enrollment Turkey	10 participants	4 participants	14 participants
Region of Enrollment United Kingdom	6 participants	1 participants	7 participants
Region of Enrollment United States	30 participants	14 participants	44 participants
Sex: Female, Male Female	57 Participants	26 Participants	83 Participants
Sex: Female, Male Male	119 Participants	64 Participants	183 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	97 / 176	49 / 90	165 / 238
serious Total, serious adverse events	15 / 176	7 / 90	41 / 238

Outcome results

Primary

Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48

Complete response was a composite endpoint defined as histological response and HBV DNA \< 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.

Time frame: Baseline; Week 48

Population: Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study medication; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Arm	Measure	Value (NUMBER)
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48	66.5 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48	12.2 percentage of participants

p-value: <0.00195% CI: [44.6, 63.6]Z-test

Secondary

Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

Time frame: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 144	-100.7 U/L	Standard Deviation 105.96
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 288	-102.3 U/L	Standard Deviation 111.68
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 96	-107.8 U/L	Standard Deviation 108.07
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 192	-101.4 U/L	Standard Deviation 108.63
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 384	-108.1 U/L	Standard Deviation 118.05
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 48	-107.2 U/L	Standard Deviation 109.44
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 432	-105.0 U/L	Standard Deviation 139.61
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 240	-95.9 U/L	Standard Deviation 117.03
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 480	-92.3 U/L	Standard Deviation 83.56
TDF-TDF	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 336	-101.9 U/L	Standard Deviation 112.72
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 480	-157.5 U/L	Standard Deviation 159.96
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 48	-106.1 U/L	Standard Deviation 118.9
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 96	-120.4 U/L	Standard Deviation 138.03
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 144	-126.2 U/L	Standard Deviation 150.46
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 192	-139.6 U/L	Standard Deviation 137.95
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 240	-134.8 U/L	Standard Deviation 135.59
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 288	-130.9 U/L	Standard Deviation 123.08
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 336	-132.3 U/L	Standard Deviation 125.81
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 384	-133.7 U/L	Standard Deviation 128.57
ADV 10 mg	Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 432	-162.1 U/L	Standard Deviation 157.83

Secondary

Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

Time frame: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

Arm	Measure	Group	Value (MEAN)	Dispersion
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 240	-6.22 log10 IU/mL	Standard Deviation 1.217
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 48	-6.17 log10 IU/mL	Standard Deviation 1.067
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 288	-6.27 log10 IU/mL	Standard Deviation 1.248
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 144	-6.32 log10 IU/mL	Standard Deviation 1.098
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 384	-6.38 log10 IU/mL	Standard Deviation 1.167
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 336	-6.35 log10 IU/mL	Standard Deviation 1.208
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 432	-6.13 log10 IU/mL	Standard Deviation 1.306
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 192	-6.30 log10 IU/mL	Standard Deviation 1.203
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 480	-6.18 log10 IU/mL	Standard Deviation 1.3
TDF-TDF	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 96	-6.26 log10 IU/mL	Standard Deviation 1.137
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 480	-6.37 log10 IU/mL	Standard Deviation 1.159
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 48	-3.93 log10 IU/mL	Standard Deviation 1.728
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 96	-6.38 log10 IU/mL	Standard Deviation 1.184
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 144	-6.31 log10 IU/mL	Standard Deviation 1.407
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 192	-6.49 log10 IU/mL	Standard Deviation 1.028
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 240	-6.45 log10 IU/mL	Standard Deviation 0.986
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 336	-6.46 log10 IU/mL	Standard Deviation 1.017
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 384	-6.28 log10 IU/mL	Standard Deviation 1.45
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 432	-6.45 log10 IU/mL	Standard Deviation 1.008
ADV 10 mg	Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 288	-6.49 log10 IU/mL	Standard Deviation 1.003

Secondary

Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240

The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).

Time frame: Baseline; Week 240

Arm	Measure	Group	Value (MEAN)	Dispersion
TDF-TDF	Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240	Knodell Necroinflammatory Score	-4.8 units on a scale	Standard Deviation 2.34
TDF-TDF	Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240	Ishak Necroinflammatory Score	-4.1 units on a scale	Standard Deviation 2.14
ADV 10 mg	Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240	Knodell Necroinflammatory Score	-5.1 units on a scale	Standard Deviation 2.43
ADV 10 mg	Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240	Ishak Necroinflammatory Score	-4.5 units on a scale	Standard Deviation 2.32

Secondary

Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48

Time frame: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set with measurements at Baseline and Week 48 were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
TDF-TDF	Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48	Knodell Necroinflammatory Score	-3.6 units on a scale	Standard Deviation 2.3
TDF-TDF	Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48	Ishak Necroinflammatory Score	-2.7 units on a scale	Standard Deviation 1.7
ADV 10 mg	Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48	Knodell Necroinflammatory Score	-3.2 units on a scale	Standard Deviation 2.35
ADV 10 mg	Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48	Ishak Necroinflammatory Score	-2.6 units on a scale	Standard Deviation 1.94

Secondary

Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

Time frame: Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

Arm	Measure	Group	Value (MEAN)	Dispersion
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 144	-0.4 U/L	Standard Deviation 21.94
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 336	-1.2 U/L	Standard Deviation 19.72
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 240	3.7 U/L	Standard Deviation 32.48
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 384	-4.4 U/L	Standard Deviation 24.87
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 192	-1.3 U/L	Standard Deviation 19.57
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 432	-4.3 U/L	Standard Deviation 24.27
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 288	-1.6 U/L	Standard Deviation 19.91
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 480	-5.5 U/L	Standard Deviation 19.28
TDF-TDF	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 96	-2.0 U/L	Standard Deviation 17.94
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 480	-7.1 U/L	Standard Deviation 39.76
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 96	-6.9 U/L	Standard Deviation 59.64
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 144	-0.7 U/L	Standard Deviation 82.7
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 192	-7.8 U/L	Standard Deviation 27.07
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 240	-8.1 U/L	Standard Deviation 22.92
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 288	-10.3 U/L	Standard Deviation 25.26
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 336	-9.3 U/L	Standard Deviation 22.69
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 384	-6.9 U/L	Standard Deviation 31.76
ADV 10 mg	Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 432	-11.6 U/L	Standard Deviation 27.09

Secondary

Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

Time frame: Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

Arm	Measure	Group	Value (MEAN)	Dispersion
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 144	-0.19 log10 IU/mL	Standard Deviation 0.475
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 336	-0.25 log10 IU/mL	Standard Deviation 0.618
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 240	-0.14 log10 IU/mL	Standard Deviation 0.706
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 384	-0.29 log10 IU/mL	Standard Deviation 0.643
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 192	-0.20 log10 IU/mL	Standard Deviation 0.565
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 432	-0.13 log10 IU/mL	Standard Deviation 0.854
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 288	-0.18 log10 IU/mL	Standard Deviation 0.762
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 480	-0.24 log10 IU/mL	Standard Deviation 0.63
TDF-TDF	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 96	-0.10 log10 IU/mL	Standard Deviation 0.422
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 480	-2.16 log10 IU/mL	Standard Deviation 1.882
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 96	-2.43 log10 IU/mL	Standard Deviation 1.724
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 144	-2.27 log10 IU/mL	Standard Deviation 1.866
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 192	-2.41 log10 IU/mL	Standard Deviation 1.662
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 240	-2.49 log10 IU/mL	Standard Deviation 1.599
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 288	-2.62 log10 IU/mL	Standard Deviation 1.679
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 336	-2.59 log10 IU/mL	Standard Deviation 1.622
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 384	-2.34 log10 IU/mL	Standard Deviation 1.821
ADV 10 mg	Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480	Week 432	-2.32 log10 IU/mL	Standard Deviation 1.694

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 144 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 96 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 96 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 97 to 144

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 96 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	No genotypic changes (wild-type virus)	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Unable to be genotyped	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Participants evaluated	2 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	3 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	No genotypic changes (wild-type virus)	2 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	2 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Participants evaluated	7 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	3 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Participants evaluated	5 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	2 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	No genotypic changes (wild-type virus)	3 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Participants evaluated	5 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)	Unable to be genotyped	1 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 192 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 144 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 144 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 145 to 192

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 144 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Unable to be genotyped	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Participants evaluated	2 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	No genotypic changes (wild-type virus)	1 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Unable to be genotyped	3 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Participants evaluated	5 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Participants evaluated	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Participants evaluated	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)	Unable to be genotyped	0 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 240 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 192 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 192 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 193 to 240

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 192 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	No genotypic changes (wild-type virus)	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Unable to be genotyped	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	2 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Participants evaluated	3 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	No genotypic changes (wild-type virus)	2 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Unable to be genotyped	1 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Participants evaluated	3 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Participants evaluated	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)	Unable to be genotyped	0 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 288 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 240 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 240 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 241 to 288

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 240 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	No genotypic changes (wild-type virus)	2 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Unable to be genotyped	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Participants evaluated	3 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)	Unable to be genotyped	0 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 336 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 288 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 288 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 289 to 336

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 288 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Unable to be genotyped	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Participants evaluated	1 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Participants evaluated	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	No genotypic changes (wild-type virus)	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)	Unable to be genotyped	0 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 384 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 336 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 336 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 337 to 384

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 336 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Unable to be genotyped	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Participants evaluated	1 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Participants evaluated	2 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	No genotypic changes (wild-type virus)	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Participants evaluated	2 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)	Unable to be genotyped	0 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 385 to 432

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 384 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Unable to be genotyped	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Participants evaluated	1 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	No genotypic changes (wild-type virus)	3 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Participants evaluated	3 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	No genotypic changes (wild-type virus)	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Participants evaluated	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)	Unable to be genotyped	0 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 433 to 480

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 432 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Unable to be genotyped	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Participants evaluated	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	No genotypic changes (wild-type virus)	2 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Participants evaluated	3 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Participants evaluated	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	No genotypic changes (wild-type virus)	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Unable to be genotyped	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	No genotypic changes (wild-type virus)	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Participants evaluated	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	0 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)	Unable to be genotyped	0 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA ≥ 400 copies/mL.

Time frame: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	2 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	No genotypic changes (wild-type virus)	7 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	13 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Unable to be genotyped	9 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Participants evaluated	31 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Unable to be genotyped	7 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Participants evaluated	75 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	8 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	17 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)	No genotypic changes (wild-type virus)	43 participants

Secondary

Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 96 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 48 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Time frame: Baseline; Weeks 49 to 96

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 48 (ie, entered the open-label phase) were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	No genotypic changes (wild-type virus)	10 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	2 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Unable to be genotyped	3 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	3 participants
TDF-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Participants evaluated	18 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	No genotypic changes (wild-type virus)	5 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Unable to be genotyped	7 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	0 participants
ADV 10 mg	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Participants evaluated	13 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	1 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Participants evaluated	16 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	2 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	No genotypic changes (wild-type virus)	12 participants
ADV-TDF	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Unable to be genotyped	1 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	No genotypic changes (wild-type virus)	3 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Changes at conserved sites in HBV polymerase	3 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Participants evaluated	10 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Changes at polymorphic sites in HBV polymerase	2 participants
ADV-TDF With Addition of FTC	Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)	Unable to be genotyped	2 participants

Secondary

Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48

ALT normalization was defined as ALT \> upper limit of normal (ULN) at baseline and within the normal range at the end of blinded treatment. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.

Time frame: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline were analyzed; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Arm	Measure	Value (NUMBER)
TDF-TDF	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48	68.0 percentage of participants
ADV 10 mg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48	54.4 percentage of participants

p-value: 0.03295% CI: [1.1, 26.1]Z-test

Secondary

Percentage of Participants With ALT Normalization at Week 96

ALT normalization was defined as ALT \> ULN at baseline and within the normal range at Week 96. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.

Time frame: Baseline; Week 96

Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Arm	Measure	Value (NUMBER)
TDF-TDF	Percentage of Participants With ALT Normalization at Week 96	65.2 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Week 96	74.4 percentage of participants

p-value: 0.195% CI: [-21.5, 1.9]Z-test

Secondary

Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384

ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.

Time frame: Baseline; Weeks 144, 192, 240, 288, 336, and 384

Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline and available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 144	60.2 percentage of participants
TDF-TDF	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 192	59.6 percentage of participants
TDF-TDF	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 240	50.0 percentage of participants
TDF-TDF	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 288	51.3 percentage of participants
TDF-TDF	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 336	46.2 percentage of participants
TDF-TDF	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 384	52.6 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 336	67.9 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 144	67.8 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 288	70.1 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 192	69.4 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 384	67.1 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384	Week 240	65.9 percentage of participants

Secondary

Percentage of Participants With ALT Normalization at Weeks 432 and 480

Time frame: Baseline; Weeks 432 and 480

Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline and with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With ALT Normalization at Weeks 432 and 480	Week 432	79.6 percentage of participants
TDF-TDF	Percentage of Participants With ALT Normalization at Weeks 432 and 480	Week 480	75.0 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Weeks 432 and 480	Week 432	78.6 percentage of participants
ADV 10 mg	Percentage of Participants With ALT Normalization at Weeks 432 and 480	Week 480	82.8 percentage of participants

Secondary

Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96

HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 96. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 96.

Time frame: Baseline; Week 96

Population: Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96	HBeAg Loss	25.9 percentage of participants
TDF-TDF	Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96	Seroconversion to Anti-HBe	22.8 percentage of participants
ADV 10 mg	Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96	HBeAg Loss	25.6 percentage of participants
ADV 10 mg	Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96	Seroconversion to Anti-HBe	22.0 percentage of participants

Comparison: This information pertains to HBeAg loss.p-value: 0.96395% CI: [-11.3, 11.9]Z-test

Comparison: This information pertains to seroconversion to anti-HBe.p-value: 0.90495% CI: [-10.4, 11.7]Z-test

Secondary

Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96

HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.

Time frame: Baseline; Week 96

Population: Participants in the Randomized and Treated Analysis Set with available data were analyzed. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96	HBsAg Loss	5.3 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96	Anti-HBs Seroconversion	4.1 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96	HBsAg Loss	5.8 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96	Anti-HBs Seroconversion	4.7 percentage of participants

Comparison: This information pertains to HBsAg loss.p-value: 0.75795% CI: [-4.8, 6.5]Z-test

Comparison: This information pertains to seroconversion to anti-HBs.p-value: 0.73395% CI: [-4.2, 5.9]Z-test

Secondary

Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480

Time frame: Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480

Population: Randomized and Treated Analysis Set. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 144	7.5 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 144	5.2 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 192	9.4 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 192	6.4 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 240	9.2 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 240	6.3 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 288	9.2 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 288	6.4 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 336	10.3 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 336	7.5 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 384	11.0 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 384	8.1 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 432	10.9 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 432	7.6 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 480	10.9 percentage of participants
TDF-TDF	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 480	8.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 480	7.9 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 144	8.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 336	7.9 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 144	6.8 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 432	10.2 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 192	7.9 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 336	7.9 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 192	6.7 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 480	10.1 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 240	8.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 384	9.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 240	8.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 432	8.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	HBsAg Loss - Week 288	8.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 384	7.9 percentage of participants
ADV 10 mg	Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480	Anti-HBs Seroconversion - Week 288	8.0 percentage of participants

Secondary

Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48

Time frame: Week 48

Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Arm	Measure	Value (NUMBER)
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48	76.1 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48	13.3 percentage of participants

p-value: <0.00195% CI: [53.8, 72.3]Z-test

Secondary

Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96

Time frame: Week 96

Population: Participants in the Randomized and Treated Analysis Set with available data were analyzed. Data included for participants who discontinued study unless the discontinuation was unrelated to protocol criteria.

Arm	Measure	Value (NUMBER)
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96	77.6 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96	77.9 percentage of participants

p-value: 0.80195% CI: [-12, 9.3]Z-test

Secondary

Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384

Time frame: Weeks 144, 192, 240, 288, 336, and 384

Population: Randomized and Treated Analysis Set. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 144	71.7 percentage of participants
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 192	67.9 percentage of participants
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 240	63.4 percentage of participants
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 288	61.3 percentage of participants
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 336	59.4 percentage of participants
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 384	56.1 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 336	62.1 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 144	70.5 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 288	64.8 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 192	71.6 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 384	60.5 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384	Week 240	66.3 percentage of participants

Secondary

Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480

Time frame: Weeks 432 and 480

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added emtricitabine to their open-label TDF regimen were included in the analysis.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480	Week 432	93.0 percentage of participants
TDF-TDF	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480	Week 480	98.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480	Week 432	100.0 percentage of participants
ADV 10 mg	Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480	Week 480	96.6 percentage of participants

Secondary

Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48

HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 48. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 48.

Time frame: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48	HBeAg Loss	22.2 percentage of participants
TDF-TDF	Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48	HBeAg Seroconversion	20.9 percentage of participants
ADV 10 mg	Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48	HBeAg Loss	17.5 percentage of participants
ADV 10 mg	Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48	HBeAg Seroconversion	17.5 percentage of participants

Comparison: This information pertains to HBeAg loss.p-value: 0.24595% CI: [-4.2, 16.4]Z-test

Comparison: This information pertains to HBeAg seroconversion.p-value: 0.36395% CI: [-5.5, 14.9]Z-test

Secondary

Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48

HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 48. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 48.

Time frame: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set with available data were analyzed.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48	HBsAg Loss	3.2 percentage of participants
TDF-TDF	Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48	HBsAg Seroconversion	1.3 percentage of participants
ADV 10 mg	Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48	HBsAg Loss	0 percentage of participants
ADV 10 mg	Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48	HBsAg Seroconversion	0 percentage of participants

Comparison: This information pertains to HBsAg loss.p-value: 0.01895% CI: [1.9, 19.9]Z-test

Comparison: This information pertains to HBsAg seroconversion.p-value: 0.14895% CI: [-1.5, 10.2]Z-test

Secondary

Percentage of Participants With Histological Response at Week 240

Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.

Time frame: Baseline; Week 240

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With Histological Response at Week 240	Yes	88.2 percentage of participants
TDF-TDF	Percentage of Participants With Histological Response at Week 240	No	11.8 percentage of participants
ADV 10 mg	Percentage of Participants With Histological Response at Week 240	Yes	89.6 percentage of participants
ADV 10 mg	Percentage of Participants With Histological Response at Week 240	No	10.4 percentage of participants

Secondary

Percentage of Participants With Histological Response at Week 48

Time frame: Baseline; Week 48

Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Percentage of Participants With Histological Response at Week 48	Yes	74.4 percentage of participants
TDF-TDF	Percentage of Participants With Histological Response at Week 48	No	25.6 percentage of participants
ADV 10 mg	Percentage of Participants With Histological Response at Week 48	Yes	67.8 percentage of participants
ADV 10 mg	Percentage of Participants With Histological Response at Week 48	No	32.2 percentage of participants

p-value: 0.3295% CI: [-5.6, 17.2]Z-test

Secondary

Ranked Assessment of Necroinflammation and Fibrosis at Week 240

Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.

Time frame: Baseline; Week 240

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Improvement - Necroinflammation	96.1 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	No Change - Necroinflammation	3.9 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Worsening - Necroinflammation	0 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Improvement - Fibrosis	56.6 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	No Change - Fibrosis	39.5 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Worsening - Fibrosis	3.9 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	No Change - Fibrosis	39.6 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Improvement - Necroinflammation	97.9 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Improvement - Fibrosis	58.3 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	No Change - Necroinflammation	2.1 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Worsening - Fibrosis	2.1 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 240	Worsening - Necroinflammation	0 percentage of participants

Secondary

Ranked Assessment of Necroinflammation and Fibrosis at Week 48

Time frame: Baseline; Week 48

Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Arm	Measure	Group	Value (NUMBER)
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Improvement - Necroinflammation	81.3 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	No Change - Necroinflammation	4.5 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Worsening - Necroinflammation	3.4 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Missing Data - Necroinflammation	10.8 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Improvement - Fibrosis	19.9 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	No Change - Fibrosis	63.6 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Worsening - Fibrosis	5.1 percentage of participants
TDF-TDF	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Missing Data - Fibrosis	11.4 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Missing Data - Fibrosis	12.2 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Improvement - Necroinflammation	78.9 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Improvement - Fibrosis	20.0 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	No Change - Necroinflammation	3.3 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Worsening - Fibrosis	6.7 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Worsening - Necroinflammation	5.6 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	No Change - Fibrosis	61.1 percentage of participants
ADV 10 mg	Ranked Assessment of Necroinflammation and Fibrosis at Week 48	Missing Data - Necroinflammation	12.2 percentage of participants

Source: ClinicalTrials.gov · Data processed: Apr 4, 2026

A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48

Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240

Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48

Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)

Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)

Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48

Percentage of Participants With ALT Normalization at Week 96

Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384

Percentage of Participants With ALT Normalization at Weeks 432 and 480

Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96

Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96

Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480

Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48

Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96

Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384

Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480

Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48

Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48

Percentage of Participants With Histological Response at Week 240

Percentage of Participants With Histological Response at Week 48

Ranked Assessment of Necroinflammation and Fibrosis at Week 240

Ranked Assessment of Necroinflammation and Fibrosis at Week 48