Efficacy and Safety Study of Tenofovir Disoproxil Fumarate (TDF) in Chinese Chronic Hepatitis B (CHB) Subjects With Advanced Fibrosis & Compensated Cirrhosis

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02224456
• Collaborator: (none)
• Enrollment: 197
• Locations: 19
• Arm: 1
• Actual Duration (Months): 68.4
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Chronic Hepatitis B infection (CHB) is known as the most frequently identified cause of liver disease that predisposes patients to the development of hepatocellular carcinoma (HCC). Active hepatitis B virus (HBV) replication is the key driver of liver injury and disease progression. Majority of Chinese patients are infected with genotype B and C HBV, which is different from Caucasian counterparts. This prospective multi-center cohort open-label study is designed to investigate the long-term effect of TDF on prevention of HCC and disease progression as well as to evaluate the efficacy and safety of long-term TDF in Chinese CHB subjects with advanced liver diseases. The study will enrol 240 subjects.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: Tenofovir disoproxil fumarate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 197 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multi-center, Cohort Study to Evaluate the Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) Therapy in Chinese Chronic Hepatitis B (CHB) Subjects With Advanced Fibrosis & Compensated Cirrhosis
• Actual Study Start Date: Mar 25, 2015
• Actual Primary Completion Date: Dec 4, 2020
• Actual Study Completion Date: Dec 4, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tenofovir Subjects will receive TDF 300 milligrams (mg) tablet once daily for 240 weeks in the study. Subjects who receive add-on rescue treatment may take LAM 100 mg, ETV 0.5 mg or LdT 600 mg per day upon investigator's decision in addition to TDF tablet.	Drug: Tenofovir disoproxil fumarate; White, almond-shaped, film-coated tablet containing 300 mg of TDF, debossed with "GILEAD" and "4331" on one side of the tablet.

Outcome Measures

Primary Outcome Measures

1. Incidence Rate of Newly Diagnosed Hepatocellular Carcinoma (HCC) at Week 240 [Week 240]

   The newly diagnosed HCC was defined as HCC cases from Week 24 to Week 240 and the participants were required to meet one of the following criteria: without HCC before Week 24; a histological diagnosis of HCC (i.e. by biopsy or at post-mortem); participants with nodules >2 centimeter (cm), identification of typical HCC characteristics (hyper-vascular in the arterial phase with washout in the portal venous or delayed phases) by 4-phase multi-detector computed tomography (CT) scan or dynamic contrast-enhanced magnetic resonance imaging (MRI); participants with nodules >1 cm, identification of typical HCC characteristics by both techniques (4-phase multi-detector CT and dynamic contrast-enhanced MRI).

2. Percentage of Participants With Disease Progression at Week 240 [Week 240]

   Disease progression was defined as the first occurrence of any one of the following criteria: 1) an increase in Childs-Pugh score of 2 or more points from Baseline; 2) an increase in Childs-Pugh score of 2 or more points, solely based on laboratory parameters (i.e. bilirubin, prothrombin time and/or albumin) confirmed between two consecutive visits at least one month apart; 3) spontaneous bacterial peritonitis (with proven sepsis); 4) renal insufficiency; 5) bleeding gastric/esophageal varices; 6) hepatocellular carcinoma; 7)liver-related death.

Secondary Outcome Measures

1. Number of Participants With Newly Diagnosed Hepatocellular Carcinoma (HCC) at Week 48, Week 96, Week 144 and Week 192 [Week 48, Week 96, Week 144 and Week 192]

   The newly diagnosed HCC was defined as HCC cases from Week 24 to Week 240 and the participants were required to meet one of the following criteria: without HCC before Week 24; a histological diagnosis of HCC (i.e. by biopsy or at post-mortem); participants with nodules >2 centimeter (cm), identification of typical HCC characteristics (hyper-vascular in the arterial phase with washout in the portal venous or delayed phases) by 4-phase multi-detector computed tomography (CT) scan or dynamic contrast-enhanced magnetic resonance imaging (MRI); participants with nodules >1 cm, identification of typical HCC characteristics by both techniques (4-phase multi-detector CT and dynamic contrast-enhanced MRI).

2. Percentage of Participants With Newly Diagnosed Hepatocellular Carcinoma (HCC) at Week 48, Week 96, Week 144, Week 192 and Week 240 [Week 48, Week 96, Week 144, Week 192 and Week 240]

   The newly diagnosed HCC was defined as HCC cases from Week 24 to Week 240 and the participants were required to meet one of the following criteria: without HCC before Week 24; a histological diagnosis of HCC (i.e. by biopsy or at post-mortem); participants with nodules >2 centimeter (cm), identification of typical HCC characteristics (hyper-vascular in the arterial phase with washout in the portal venous or delayed phases) by 4-phase multi-detector computed tomography (CT) scan or dynamic contrast-enhanced magnetic resonance imaging (MRI); participants with nodules >1 cm, identification of typical HCC characteristics by both techniques (4-phase multi-detector CT and dynamic contrast-enhanced MRI).The cumulative percentage of participants with newly diagnosed Hepatocellular Carcinoma has been presented along with 95% confidence interval (CI) (Wald method).

3. Percentage of Participants With Disease Progression at Week 48, Week 96, Week 144, Week 192 and Week 240 [Week 48, Week 96, Week 144, Week 192 and Week 240]

   Disease progression was defined as the first occurrence of any one of the following criteria: 1) an increase in Childs-Pugh score of 2 or more points from Baseline; 2) an increase in Childs-Pugh score of 2 or more points, solely based on laboratory parameters (i.e. bilirubin, prothrombin time and/or albumin) confirmed between two consecutive visits at least one month apart; 3) spontaneous bacterial peritonitis (with proven sepsis); 4) renal insufficiency; 5) bleeding gastric/oesophageal varices; 6) hepatocellular carcinoma; 7) liver-related death. The cumulative percentage of participants with disease progression has been presented along with 95% CI (Wald method).

4. Mean Change From Baseline in Liver Stiffness Measure at Week 48, Week 96, Week 144, Week 192 and Week 240 [Baseline (Day 0), Week 48, Week 96, Week 144, Week 192 and Week 240]

   Liver stiffness measure was obtained by a non-invasive transient elastography using FibroScan. Baseline is defined as the last assessment (Day 0) before administration of the study drug. Change from Baseline is defined as post-dose visit value minus Baseline value

5. Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <20 International Units Per Milliliter (IU/mL) at Weeks 48, 96, 144, 192 and 240 [Week 48, Week 96, Week 144, Week 192 and Week 240]

   Serum samples were collected for the analysis of HBV DNA levels using Roche Cobas Taqman HBV test. Confidence interval was calculated by normal approximation and continuity correction method.

6. Change From Baseline in Logarithm to the Base 10 (Log 10) Serum HBV DNA [Baseline (Day 0) and Week 48, Week 96, Week 144, Week 192 and Week 240]

   Serum samples were collected for the analysis of HBV DNA levels. Baseline is defined as the last assessment (Day 0) before administration of the study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

7. Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48, Week 96, Week 144, Week 192 and Week 240 in Participants Who Had Abnormal ALT at Baseline [Week 48, Week 96, Week 144, Week 192 and Week 240]

   Blood samples were collected for evaluation of ALT at indicated time points. ALT normalization is defined as ALT outside the normal range at Baseline and within the normal range at Week 48, Week 96, Week 144, Week 192 and Week 240. Normal range of ALT is 7 to 56 International Units per liter. Percentage of participants with ALT normalization at Weeks 48, 96, 144, 192 and 240 in participants who had abnormal ALT at Baseline (Day 0) have been presented. Confidence interval was calculated using normal approximation and continuity correction method.

8. Percentage of Hepatitis B e Antigen (HBeAg) Positive Participants Achieving HBeAg Loss, HBeAg Seroconversion at Week 48, Week 96, Week 144, Week 192 and Week 240. [Week 48, Week 96, Week 144, Week 192 and Week 240]

   Serological response was assessed at Week 48, Week 96, Week 144, Week 192 and Week 240 in participants with Positive HBeAg at Baseline (Day 0). It was presented as HBeAg Loss and HBeAg Seroconversion. HBeAg Loss was defined as HBeAg changed to be negative. HBeAg seroconversion was defined as HBeAg changed to negative and HBeAb was positive. Confidence interval was calculated using normal approximation and continuity correction method.

9. Percentage of HBeAg Negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Week 48, Week 96, Week 144, Week 192 and Week 240 [Week 48, Week 96, Week 144, Week 192 and Week 240]

   Serological response was assessed at Week 48, Week 96, Week 144, Week 192 and Week 240 in participants with negative HBeAg at Baseline (Day 0). HBsAg Loss was defined as HBsAg changed to be negative. HBsAg seroconversion was defined as HBsAg changed to negative and HBsAb was positive.

10. Percentage of Participants Who Experienced Viral Breakthrough [Week 48, Week 96, Week 144, Week 192 and Week 240]

    Viral breakthrough was defined as >=1 log10 increase in HBV DNA from nadir determined by two sequential HBV DNA measurements. Percentage of Participants who experienced viral breakthrough at Week 48, Week 96, Week 144, Week 192 and Week 240 is presented.

11. Percentage of Participants With Histological Improvement at Week 216 [Week 216]

    The Knodell scoring system, also called the Histologic Activity Index (HAI), classifies liver biopsy specimens according to scores into 4 categories of histologic features: (I) Periportal or periseptal interface hepatitis (piecemeal necrosis) (scores from 0, 1, 2, 3, 4 or 10); (II) Confluent necrosis (scores from 0, 1, 3, 4, 5, 6 or 10); (III) Focal (spotty) lytic necrosis, apoptosis and focal inflammation (scores from 0, 1, 2, 3, 4 or 10); (IV) Portal inflammation (scores from 0, 1, 2, 3, 4 or 10). Histological improvement is considered as a reduction of two or more points in the Knodell necroinflammatory score with no increase in fibrosis.

12. Percentage of Participants With Cirrhosis Reversal at Week 216 [Week 216]

    Cirrhosis reversal was defined as a reduction of one or more points in the Ishak score with no evidence of cirrhosis. The Ishak liver fibrosis score ranges from 0 indicating no fibrosis to 6 indicating cirrhosis.

13. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs [Up to Week 240]

    An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is defined as AE that occurred on or after the first dose date of study drug. SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement or events possible drug-induced liver injury with hyperbilirubinemia.

14. Change From Baseline in Hematology Parameters: White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, WBC, lymphocytes, monocytes, neutrophils and platelets. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

15. Change From Baseline in Hemoglobin (Hb) [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze Hb values. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

16. Change From Baseline in Red Blood Cells (RBC) [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze RBC values. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

17. Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-Glutamyltransferase (GGT), Creatinine Phosphokinase (CK), Lactose Dehydrogenase (LDH) [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, CK, LDH. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

18. Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Serum Creatinine [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze the chemistry parameters: total billirubin,direct bilirubin and serum creatinine. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

19. Change From Baseline in Chemistry Parameters: Albumin and Total Protein [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze the chemistry parameters: albumin and total protein. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

20. Change From Baseline in Chemistry Parameter: Blood Urea Nitrogen (BUN), Potassium, Sodium, Chloridion, Phosphorus, Calcium and Fasting Blood Glucose [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze the chemistry parameters: BUN, potassium, sodium, chloridion, phosphorus,calcium and fasting blood glucose. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

21. Change From Baseline in Chemistry Parameters: Creatinine Clearance Rate [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze the chemistry parameters: creatinine clearance rate. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

22. Change From Baseline in Chemistry Parameters: Estimated Glomerular Filtration Rate (eGFR) [Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240]

    Blood samples were collected to analyze the chemistry parameters: eGFR. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-60 years(inclusive);

• Presence of HBsAg in serum at screening and for at least 6 months before screening assessment;

• Serum HBV DNA>=2000 IU/mL if HBeAg positive at screening (with or without ALT elevation); or serum HBV DNA>=200IU/mL if HBeAg negative at screening (with or without ALT elevation);

• Clinically diagnosed as advanced fibrosis or compensated cirrhosis defined as both of following : liver stiffness measure (LSM) >12.4 kiloPascals (kpa) (ALT> Upper limit of normal [ULN]) or LSM>9.0 kpa (ALT<=ULN); One of following: Liver biopsy showing advanced fibrosis or cirrhosis (Ishak score >=4, within the previous 6 months before screening and provided that no treatment likely to improve liver histology has been taken since). The slides must be available for review by an independent histopathologist; Endoscopy-proven gastroesophageal or gastric varices, non-cirrhotic portal hypertension excluded; Abdominal ultrasound or CT found changes indicating cirrhosis, irregular liver surface or nodularity, with/without splenomegaly (depth of spleen>4.0cm or spleen length>13cm); Blood platelets <100 x10^9/L (and other causes of thrombocytopenia excluded);

• Ability to give written informed consent;

• A female is eligible to enter and participate in this study if she is of: non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal), or Child-bearing potential, has a negative urine pregnancy test at screening, and agrees to one of the following methods for avoidance of pregnancy during the period of the study and until 30 days after last dose of study medication: Oral contraceptive, either combined or progestogen alone; Injectable progestogen; Implants of levonorgestrel; Oestrogenic vaginal ring; Percutaneous contraceptive patches; Intrauterine device (IUD) or intrauterine system (IUS) showing that the expected failure rate is less than 1% per year as stated in the

IUD or IUS product label; Has a male partner who is sterilised; Double barrier method:

condom and an occlusive cap (diaphragm orcervical/vault caps) with a vaginal spermicidal agent (foam/gel/film /cream/suppository).

• Agreement not to participate in any other investigational trials or to undertake other HBV systemic antiviral or interferon (IFN) regimens during participation in this study.

Exclusion Criteria:

• Hepatocellular carcinoma as evidenced by one of the following: Suspicious foci on ultrasound or radiological examination; Normal ultrasound serum alpha-fetoprotein >50 nanograms (ng)/mL at screening.

• Serum ALT >10 times ULN at screening or history of acute exacerbation leading to transient decompensation;

• Documented co-infection with hepatitis A (HAV), hepatitis C (HCV), hepatitis delta virus (HDV), hepatitis E virus (HEV) or human immunodeficiency virus (HIV). For HCV co-infection, subjects who are anti-HCV positive and in whom HCV ribonucleic acid (RNA) is undetectable are considered to be not eligible for enrolment.

• Evidence of active liver disease due to autoimmune hepatitis (antinuclear antibody (ANA) titre >1:160).

• Decompensated liver disease as indicated by any of the following: serum bilirubin >1.5 xULN prothrombin time activity <60% or International normalized ratio (INR)>1.5; serum albumin <32 grams per liter (g/L); history of previous clinical hepatic decompensation (e.g., ascites, variceal bleeding, or encephalopathy);

• Planned for liver transplantation or previous liver transplantation;

• Creatinine clearance less than 70 mL/minute (min);

• Haemoglobin <10 g/deciliter (dL), white blood cell (WBC) count <1.5 x 10^{9/liter (L), platelets <=50 x 10}9/L;

• Any serious or active medical or psychiatric illnesses other than hepatitis B which, in the opinion of the Investigator, would interfere with subject treatment, assessment or compliance with the protocol. This would include any uncontrolled clinically significant renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, pathological fractures or cancer;

• Active alcohol or drug abuse or history of alcohol or drug abuse considered by the Investigator to be sufficient to hinder compliance with treatment, participation in the study or interpretation of results;

• A female who is breastfeeding or plan to breastfeed;

• Use of immunosuppressive therapy, immunomodulatory therapy (including IFN or thymosin alpha), systemic cytotoxic agents, chronic antiviral agents including Chinese herbal medicines known to have activity against HBV (e.g., lamivudine (LAM), adefovir, entecavir (ETV), telbivudine (LdT) or hepatitis B immunoglobulin (HBIg)) within the previous 6 months prior to screening into this study;

• Have ever received TDF or any medicinal products containing the above mentioned antiviral agents or any investigative anti-HBV treatments (e.g., emtricitabine (FTC), (2R,4R)-4-(2,6-Diaminopurin-9-yl)-1,3-dioxolan-2-yl]methanol (DAPD) and 1-(2-fluoro-5-methyl-beta, Larabinofuranosyl) uracil (L-FMAU));

• History of hypersensitivity to nucleoside and/or nucleotide analogues and/or any component of study medication;

• Therapy with nephrotoxic drugs (e.g., aminoglycosides, amphotercin B, vancomycin, cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal excretion (e.g., probenecid) within 2 months prior to study screening or the expectation that subject will receive any of these during the course of the study;

• Inability to comply with study requirements as determined by the study Investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Guangzhou	Guangdong	China	510060
2	GSK Investigational Site	Wuhan	Hubei	China	430022
3	GSK Investigational Site	Nanjing	Jiangsu	China	210002
4	GSK Investigational Site	Nanjing	Jiangsu	China	210003
5	GSK Investigational Site	Changchun	Jilin	China	130000
6	GSK Investigational Site	Xian	Shanxi	China	710038
7	GSK Investigational Site	Chengdu	Sichuan	China	610041
8	GSK Investigational Site	Beijing		China	100044
9	GSK Investigational Site	Beijing		China	100050
10	GSK Investigational Site	Beijing		China	100069
11	GSK Investigational Site	Chongqing		China	400038
12	GSK Investigational Site	Hangzhou		China	310000
13	GSK Investigational Site	Jinan		China	250021
14	GSK Investigational Site	Shanghai		China	200025
15	GSK Investigational Site	Shanghai		China	200040
16	GSK Investigational Site	Shanghai		China	201508
17	GSK Investigational Site	Taiyuan		China	030001
18	GSK Investigational Site	Xi'an		China	710061
19	GSK Investigational Site	Zhengzhou		China	450000

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Sep 9, 2016
• Statistical Analysis Plan - Feb 26, 2021

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02224456
• Other Study ID Numbers: 201213
• First Posted: Aug 25, 2014
• Last Update Posted: Feb 14, 2022
• Last Verified: Nov 1, 2021

• Keywords provided by GlaxoSmithKline: Tenofovir disoproxil fumarate; hepatocellular carcinoma; chronic hepatitis B; Cirrhosis
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Fibrosis; Tenofovir

Study Results

Participant Flow

Recruitment Details	This study was conducted to evaluate the efficacy and safety of 300 milligram (mg) Tenofovir Disoproxil Fumarate (TDF) therapy in Chinese chronic hepatitis B (CHB) participants with advanced fibrosis and compensated cirrhosis
Pre-assignment Detail	A total of 266 participants were screened, of which 197 entered the study.

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Period Title: Overall Study
STARTED	197
COMPLETED	161
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Overall Participants	195
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.3 (9.80)
Sex: Female, Male (Count of Participants)
Female	47 24.1%
Male	148 75.9%
Race/Ethnicity, Customized (Count of Participants)
Asian	195 100%

Outcome Measures

1. Primary Outcome

Title	Incidence Rate of Newly Diagnosed Hepatocellular Carcinoma (HCC) at Week 240
Description	The newly diagnosed HCC was defined as HCC cases from Week 24 to Week 240 and the participants were required to meet one of the following criteria: without HCC before Week 24; a histological diagnosis of HCC (i.e. by biopsy or at post-mortem); participants with nodules >2 centimeter (cm), identification of typical HCC characteristics (hyper-vascular in the arterial phase with washout in the portal venous or delayed phases) by 4-phase multi-detector computed tomography (CT) scan or dynamic contrast-enhanced magnetic resonance imaging (MRI); participants with nodules >1 cm, identification of typical HCC characteristics by both techniques (4-phase multi-detector CT and dynamic contrast-enhanced MRI).
Time Frame	Week 240

Outcome Measure Data

Analysis Population Description

Modified Intent-to-treat (mITT) Population consisted of all recruited participants who received at least one dose of study medication.

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	195
Number [Events per person-year]	6.045

2. Primary Outcome

Title	Percentage of Participants With Disease Progression at Week 240
Description	Disease progression was defined as the first occurrence of any one of the following criteria: 1) an increase in Childs-Pugh score of 2 or more points from Baseline; 2) an increase in Childs-Pugh score of 2 or more points, solely based on laboratory parameters (i.e. bilirubin, prothrombin time and/or albumin) confirmed between two consecutive visits at least one month apart; 3) spontaneous bacterial peritonitis (with proven sepsis); 4) renal insufficiency; 5) bleeding gastric/esophageal varices; 6) hepatocellular carcinoma; 7)liver-related death.
Time Frame	Week 240

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	195
Number [Percentage of participants]	7.2 3.7%

3. Secondary Outcome

Title	Number of Participants With Newly Diagnosed Hepatocellular Carcinoma (HCC) at Week 48, Week 96, Week 144 and Week 192
Description	The newly diagnosed HCC was defined as HCC cases from Week 24 to Week 240 and the participants were required to meet one of the following criteria: without HCC before Week 24; a histological diagnosis of HCC (i.e. by biopsy or at post-mortem); participants with nodules >2 centimeter (cm), identification of typical HCC characteristics (hyper-vascular in the arterial phase with washout in the portal venous or delayed phases) by 4-phase multi-detector computed tomography (CT) scan or dynamic contrast-enhanced magnetic resonance imaging (MRI); participants with nodules >1 cm, identification of typical HCC characteristics by both techniques (4-phase multi-detector CT and dynamic contrast-enhanced MRI).
Time Frame	Week 48, Week 96, Week 144 and Week 192

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	195
Week 48	0 0%
Week 96	0 0%
Week 144	4 2.1%
Week 192	9 4.6%

4. Secondary Outcome

Title	Percentage of Participants With Newly Diagnosed Hepatocellular Carcinoma (HCC) at Week 48, Week 96, Week 144, Week 192 and Week 240
Description	The newly diagnosed HCC was defined as HCC cases from Week 24 to Week 240 and the participants were required to meet one of the following criteria: without HCC before Week 24; a histological diagnosis of HCC (i.e. by biopsy or at post-mortem); participants with nodules >2 centimeter (cm), identification of typical HCC characteristics (hyper-vascular in the arterial phase with washout in the portal venous or delayed phases) by 4-phase multi-detector computed tomography (CT) scan or dynamic contrast-enhanced magnetic resonance imaging (MRI); participants with nodules >1 cm, identification of typical HCC characteristics by both techniques (4-phase multi-detector CT and dynamic contrast-enhanced MRI).The cumulative percentage of participants with newly diagnosed Hepatocellular Carcinoma has been presented along with 95% confidence interval (CI) (Wald method).
Time Frame	Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	195
Week 48	0 0%
Week 96	0 0%
Week 144	2.1 1.1%
Week 192	4.6 2.4%
Week 240	5.6 2.9%

5. Secondary Outcome

Title	Percentage of Participants With Disease Progression at Week 48, Week 96, Week 144, Week 192 and Week 240
Description	Disease progression was defined as the first occurrence of any one of the following criteria: 1) an increase in Childs-Pugh score of 2 or more points from Baseline; 2) an increase in Childs-Pugh score of 2 or more points, solely based on laboratory parameters (i.e. bilirubin, prothrombin time and/or albumin) confirmed between two consecutive visits at least one month apart; 3) spontaneous bacterial peritonitis (with proven sepsis); 4) renal insufficiency; 5) bleeding gastric/oesophageal varices; 6) hepatocellular carcinoma; 7) liver-related death. The cumulative percentage of participants with disease progression has been presented along with 95% CI (Wald method).
Time Frame	Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	195
Week 48	2.1 1.1%
Week 96	2.6 1.3%
Week 144	4.1 2.1%
Week 192	7.2 3.7%
Week 240	7.2 3.7%

6. Secondary Outcome

Title	Mean Change From Baseline in Liver Stiffness Measure at Week 48, Week 96, Week 144, Week 192 and Week 240
Description	Liver stiffness measure was obtained by a non-invasive transient elastography using FibroScan. Baseline is defined as the last assessment (Day 0) before administration of the study drug. Change from Baseline is defined as post-dose visit value minus Baseline value
Time Frame	Baseline (Day 0), Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles.

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	182
Week 48, n=182	-3.3 (4.84)
Week 96, n= 176	-4.7 (5.60)
Week 144, n= 175	-5.1 (5.85)
Week 192, n=167	-5.1 (7.82)
Week 240, n= 131	-6.2 (5.55)

7. Secondary Outcome

Title	Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <20 International Units Per Milliliter (IU/mL) at Weeks 48, 96, 144, 192 and 240
Description	Serum samples were collected for the analysis of HBV DNA levels using Roche Cobas Taqman HBV test. Confidence interval was calculated by normal approximation and continuity correction method.
Time Frame	Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles.

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, n=191	81.2 41.6%
Week 96, n=188	88.8 45.5%
Week 144, n=185	94.1 48.3%
Week 192, n=174	97.7 50.1%
Week 240, n=160	99.4 51%

8. Secondary Outcome

Title	Change From Baseline in Logarithm to the Base 10 (Log 10) Serum HBV DNA
Description	Serum samples were collected for the analysis of HBV DNA levels. Baseline is defined as the last assessment (Day 0) before administration of the study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles.

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, n=191	-4.2 (1.40)
Week 96, n=188	-4.3 (1.44)
Week 144, n=185	-4.3 (1.48)
Week 192, n=174	-4.2 (1.50)
Week 240, n=160	-4.3 (1.46)

9. Secondary Outcome

Title	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48, Week 96, Week 144, Week 192 and Week 240 in Participants Who Had Abnormal ALT at Baseline
Description	Blood samples were collected for evaluation of ALT at indicated time points. ALT normalization is defined as ALT outside the normal range at Baseline and within the normal range at Week 48, Week 96, Week 144, Week 192 and Week 240. Normal range of ALT is 7 to 56 International Units per liter. Percentage of participants with ALT normalization at Weeks 48, 96, 144, 192 and 240 in participants who had abnormal ALT at Baseline (Day 0) have been presented. Confidence interval was calculated using normal approximation and continuity correction method.
Time Frame	Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles.

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	97
Week 48, n=97	63.9 32.8%
Week 96, n= 97	66.0 33.8%
Week 144, n=96	70.8 36.3%
Week 192, n=93	82.8 42.5%
Week 240, n=87	82.8 42.5%

10. Secondary Outcome

Title	Percentage of Hepatitis B e Antigen (HBeAg) Positive Participants Achieving HBeAg Loss, HBeAg Seroconversion at Week 48, Week 96, Week 144, Week 192 and Week 240.
Description	Serological response was assessed at Week 48, Week 96, Week 144, Week 192 and Week 240 in participants with Positive HBeAg at Baseline (Day 0). It was presented as HBeAg Loss and HBeAg Seroconversion. HBeAg Loss was defined as HBeAg changed to be negative. HBeAg seroconversion was defined as HBeAg changed to negative and HBeAb was positive. Confidence interval was calculated using normal approximation and continuity correction method.
Time Frame	Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles.)

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	94
Week 48, HBeAg Loss, n=94	18.1 9.3%
Week 48, HBeAg Seroconversion, n=94	9.6 4.9%
Week 96, HBeAg , n=94	33.0 16.9%
Week 96, HBeAg Seroconversion, n=94	14.9 7.6%
Week 144, HBeAg Loss, n=90	35.6 18.3%
Week 144, HBeAg Seroconversion, n=90	14.4 7.4%
Week 192, HBeAg Loss, n=90	47.8 24.5%
Week 192, HBeAg Seroconversion, n=90	16.7 8.6%
Week 240, HBeAg Loss, n=82	51.2 26.3%
Week 240, HBeAg Seroconversion, n=82	23.2 11.9%

11. Secondary Outcome

Title	Percentage of HBeAg Negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Week 48, Week 96, Week 144, Week 192 and Week 240
Description	Serological response was assessed at Week 48, Week 96, Week 144, Week 192 and Week 240 in participants with negative HBeAg at Baseline (Day 0). HBsAg Loss was defined as HBsAg changed to be negative. HBsAg seroconversion was defined as HBsAg changed to negative and HBsAb was positive.
Time Frame	Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles.)

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	97
Week 48, HBsAg Loss, n=97	1.0 0.5%
Week 48, HBsAg Seroconversion, n=97	1.0 0.5%
Week 96, HBsAg , n=93	0 0%
Week 96, HBsAg Seroconversion, n=93	0 0%
Week 144, HBsAg Loss, n=93	3.2 1.6%
Week 144, HBsAg Seroconversion, n=93	0 0%
Week 192, HBsAg Loss, n=89	4.5 2.3%
Week 192, HBsAg Seroconversion, n=89	2.2 1.1%
Week 240, HBsAg Loss, n=77	5.2 2.7%
Week 240, HBsAg Seroconversion, n=77	1.3 0.7%

12. Secondary Outcome

Title	Percentage of Participants Who Experienced Viral Breakthrough
Description	Viral breakthrough was defined as >=1 log10 increase in HBV DNA from nadir determined by two sequential HBV DNA measurements. Percentage of Participants who experienced viral breakthrough at Week 48, Week 96, Week 144, Week 192 and Week 240 is presented.
Time Frame	Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles.)

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	195
Week 48, n=195	0 0%
Week 96, n=195	0 0%
Week 144, n=185	0.5 0.3%
Week 192, n=180	1.1 0.6%
Week 240, n=161	0.6 0.3%

13. Secondary Outcome

Title	Percentage of Participants With Histological Improvement at Week 216
Description	The Knodell scoring system, also called the Histologic Activity Index (HAI), classifies liver biopsy specimens according to scores into 4 categories of histologic features: (I) Periportal or periseptal interface hepatitis (piecemeal necrosis) (scores from 0, 1, 2, 3, 4 or 10); (II) Confluent necrosis (scores from 0, 1, 3, 4, 5, 6 or 10); (III) Focal (spotty) lytic necrosis, apoptosis and focal inflammation (scores from 0, 1, 2, 3, 4 or 10); (IV) Portal inflammation (scores from 0, 1, 2, 3, 4 or 10). Histological improvement is considered as a reduction of two or more points in the Knodell necroinflammatory score with no increase in fibrosis.
Time Frame	Week 216

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	31
Number (95% Confidence Interval) [Percentage of participants]	45.2 23.2%

14. Secondary Outcome

Title	Percentage of Participants With Cirrhosis Reversal at Week 216
Description	Cirrhosis reversal was defined as a reduction of one or more points in the Ishak score with no evidence of cirrhosis. The Ishak liver fibrosis score ranges from 0 indicating no fibrosis to 6 indicating cirrhosis.
Time Frame	Week 216

Outcome Measure Data

Analysis Population Description

mITT Population. Only those participants with data available at the specified data points were analyzed

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	31
Number (95% Confidence Interval) [Percentage of participants]	41.9 21.5%

15. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs
Description	An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is defined as AE that occurred on or after the first dose date of study drug. SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement or events possible drug-induced liver injury with hyperbilirubinemia.
Time Frame	Up to Week 240

Outcome Measure Data

Analysis Population Description

Safety Analysis Population was defined as all participants who received at least one dose of study medication and have at least one post Baseline safety assessment.

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	195
Any TEAEs	139 71.3%
Serious TEAE	34 17.4%
Non-serious TEAE	129 66.2%

16. Secondary Outcome

Title	Change From Baseline in Hematology Parameters: White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets
Description	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, WBC, lymphocytes, monocytes, neutrophils and platelets. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, WBC, n=191	0.02 (1.264)
Week 96, WBC, n=188	0.09 (1.380)
Week 144, WBC, n=185	-0.12 (1.378)
Week 192, WBC, n=179	0.12 (1.412)
Week 240, WBC, n=160	0.06 (1.434)
Week 48, Neutrophils, n=191	0.08 (1.051)
Week 96, Neutrophils, n=188	0.21 (1.184)
Week 144, Neutrophils, n=185	0.07 (1.162)
Week 192, Neutrophils, n=179	0.26 (1.197)
Week 240, Neutrophils, n=160	0.28 (1.194)
Week 48, Lymphocytes, n=191	0.00 (0.438)
Week 96, Lymphocytes, n=188	-0.06 (0.511)
Week 144, Lymphocytes, n=185	-0.13 (0.422)
Week 192, Lymphocytes, n=179	-0.10 (0.442)
Week 240, Lymphocytes, n=160	-0.15 (0.483)
Week 48, Monocytes, n=191	-0.032 (0.1056)
Week 96, Monocytes, n=188	-0.033 (0.1113)
Week 144, Monocytes, n=185	-0.035 (0.1244)
Week 192, Monocytes, n=179	-0.025 (0.1162)
Week 240, Monocytes, n=160	-0.005 (0.1664)
Week 48, Eosinophils, n=191	-0.02 (0.114)
Week 96, Eosinophils, n=188	-0.02 (0.164)
Week 144, Eosinophils, n=185	-0.04 (0.237)
Week 192, Eosinophils, n=179	-0.03 (0.248)
Week 240, Eosinophils, n=160	-0.03 (0.251)
Week 48, Basophils, n=191	0.00 (0.017)
Week 96, Basophils, n=188	0.00 (0.019)
Week 144, Basophils, n=184	0.01 (0.025)
Week 192, Basophils, n=179	0.01 (0.021)
Week 240, Basophils, n=160	0.01 (0.033)
Week 48, Platelets, n=191	7.8 (31.45)
Week 96, Platelets, n=188	14.1 (32.46)
Week 144, Platelets, n=185	20.6 (42.02)
Week 192, Platelets, n=179	25.7 (42.56)
Week 240, Platelets, n=160	26.6 (38.39)

17. Secondary Outcome

Title	Change From Baseline in Hemoglobin (Hb)
Description	Blood samples were collected to analyze Hb values. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, n=191	-0.6 (10.12)
Week 96, n=188	0.2 (11.63)
Week 144, n=185	0.9 (11.26)
Week 192, n=179	-0.3 (12.61)
Week 240, n=160	1.2 (12.71)

18. Secondary Outcome

Title	Change From Baseline in Red Blood Cells (RBC)
Description	Blood samples were collected to analyze RBC values. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, n=191	0.11 (0.306)
Week 96, n=188	0.13 (0.344)
Week 144, n=185	0.15 (0.340)
Week 192, n=179	0.10 (0.363)
Week 240, n=160	0.12 (0.341)

19. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-Glutamyltransferase (GGT), Creatinine Phosphokinase (CK), Lactose Dehydrogenase (LDH)
Description	Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, CK, LDH. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, ALT, n=190	-23.98 (59.452)
Week 96, ALT, n=187	-28.99 (56.983)
Week 144, ALT, n=185	-28.99 (56.983)
Week 192, ALT, n=178	-31.79 (57.955)
Week 240, ALT, n=158	-32.02 (63.157)
Week 48, AST, n=191	-14.69 (36.674)
Week 96, AST, n=188	-17.97 (36.057)
Week 144, AST, n=184	-18.10 (36.809)
Week 192, AST, n=178	-19.82 (36.312)
Week 240, AST, n=158	-20.24 (43.908)
Week 48, ALP, n=190	10.18 (20.288)
Week 96, ALP, n=188	2.60 (28.233)
Week 144, ALP, n=185	-2.20 (26.555)
Week 192, ALP, n=177	-0.94 (31.604)
Week 240, ALP, n=158	-4.68 (27.596)
Week 48, GGT, n=190	-17.88 (32.753)
Week 96, GGT, n=188	-22.20 (34.866)
Week 144, GGT, n=185	-24.69 (39.764)
Week 192, GGT, n=175	-24.07 (38.609)
Week 240, GGT, n=152	-27.26 (42.932)
Week 48 CK, n=188	10.51 (103.515)
Week 96, CK, n=185	16.77 (141.961)
Week 144, CK, n=182	5.96 (101.897)
Week 192, CK, n=173	13.72 (106.986)
Week 240, CK, n=156	2.79 (105.349)
Week 48, LDH, n=187	-10.62 (52.851)
Week 96, LDH, n=185	-10.21 (48.112)
Week 144, LDH, n=180	3.34 (73.047)
Week 192, LDH, n=172	-18.45 (87.931)
Week 240, LDH, n=155	25.79 (87.464)

20. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Serum Creatinine
Description	Blood samples were collected to analyze the chemistry parameters: total billirubin,direct bilirubin and serum creatinine. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, total bilirubin, n=191	-1.485 (7.1347)
Week 96, total bilirubin, n=188	-1.823 (6.7167)
Week 144, total bilirubin, n=185	-2.665 (7.1281)
Week 192, total bilirubin, n=177	-2.791 (6.9230)
Week 240, total bilirubin, n=158	-1.772 (6.9786)
Week 48, direct bilirubin, n=191	-0.296 (3.1229)
Week 96, direct bilirubin, n=188	-0.462 (3.1875)
Week 144, direct bilirubin, n=185	-0.713 (3.4898)
Week 192, direct bilirubin, n=178	-0.780 (3.5942)
Week 240, direct bilirubin, n=157	-0.599 (3.5608)
Week 48, serum creatinine, n=191	1.03 (7.020)
Week 96, serum creatinine, n=188	1.10 (7.597)
Week 144, serum creatinine, n=184	0.76 (9.122)
Week 192, serum creatinine, n=178	1.37 (8.591)
Week 240, serum creatinine, n=159	1.35 (9.879)

21. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Albumin and Total Protein
Description	Blood samples were collected to analyze the chemistry parameters: albumin and total protein. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, albumin, n=191	1.06 (3.063)
Week 96, albumin, n=188	1.23 (3.313)
Week 144, albumin, n=185	1.86 (3.675)
Week 192, albumin, n=175	1.65 (3.780)
Week 240, albumin, n=158	1.81 (3.790)
Week 48, total protein, n=191	-1.01 (5.273)
Week 96, total protein, n=188	-0.21 (5.397)
Week 144, total protein, n=185	0.27 (5.065)
Week 192, total protein, n=175	-0.94 (5.175)
Week 240, total protein, n=158	-1.61 (5.829)

22. Secondary Outcome

Title	Change From Baseline in Chemistry Parameter: Blood Urea Nitrogen (BUN), Potassium, Sodium, Chloridion, Phosphorus, Calcium and Fasting Blood Glucose
Description	Blood samples were collected to analyze the chemistry parameters: BUN, potassium, sodium, chloridion, phosphorus,calcium and fasting blood glucose. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, BUN, n=191	-0.046 (1.1067)
Week 96, BUN, n=188	0.000 (1.1875)
Week 144, BUN, n=184	0.037 (1.0892)
Week 192, BUN, n=178	0.143 (1.1234)
Week 240, BUN, n=155	0.131 (1.1358)
Week 48, Potassium, n=191	-0.001 (0.3703)
Week 96, Potassium, n=186	0.002 (0.3230)
Week 144, Potassium, n=184	-0.039 (0.3871)
Week 192, Potassium, n=178	0.015 (0.4223)
Week 240, Potassium, n=158	-0.013 (0.3946)
Week 48, Sodium, n=191	0.21 (3.495)
Week 96, Sodium, n=186	-0.02 (3.121)
Week 144, Sodium, n=184	0.35 (2.730)
Week 192, Sodium, n=178	0.38 (2.998)
Week 240, Sodium, n=158	-0.13 (2.707)
Week 48, Chloridion, n=191	-0.13 (3.600)
Week 96, Chloridion, n=186	0.40 (3.535)
Week 144, Chloridion, n=183	0.35 (3.492)
Week 192, Chloridion, n=178	0.77 (3.142)
Week 240, Chloridion, n=158	0.49 (3.364)
Week 48, Phosphorus, n=190	-0.044 (0.1724)
Week 96, Phosphorus, n=187	-0.038 (0.1632)
Week 144, Phosphorus, n=184	-0.037 (0.1955)
Week 192, Phosphorus, n=175	-0.059 (0.1876)
Week 240, Phosphorus, n=159	-0.042 (0.2009)
Week 48, Calcium, n=190	-0.023 (0.1513)
Week 96, Calcium, n=187	-0.006 (0.1652)
Week 144, Calcium, n=184	-0.022 (0.1605)
Week 192, Calcium, n=178	-0.004 (0.1470)
Week 240, Calcium, n=158	-0.006 (0.1558)
Week 48, Fasting Blood Glucose, n=191	-0.162 (0.7154)
Week 96, Fasting Blood Glucose, n=188	-0.109 (0.7139)
Week 144, Fasting Blood Glucose, n=185	-0.094 (0.8979)
Week 192, Fasting Blood Glucose, n=177	-0.052 (0.7548)
Week 240, Fasting Blood Glucose, n=158	0.052 (1.2197)

23. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Creatinine Clearance Rate
Description	Blood samples were collected to analyze the chemistry parameters: creatinine clearance rate. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	190
Week 48, n=190	-3.064 (11.5995)
Week 96, n=188	-4.214 (12.7883)
Week 144, n=184	-4.324 (15.3937)
Week 192, n=177	-6.599 (13.8858)
Week 240, n=155	-6.658 (16.5351)

24. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Estimated Glomerular Filtration Rate (eGFR)
Description	Blood samples were collected to analyze the chemistry parameters: eGFR. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day 0) and at Week 48, Week 96, Week 144, Week 192 and Week 240

Outcome Measure Data

Analysis Population Description

Safety analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
Measure Participants	191
Week 48, n=191	-0.86 (6.581)
Week 96, n=188	-0.87 (7.078)
Week 144, n=185	-0.68 (8.368)
Week 192, n=180	-1.06 (8.442)
Week 240, n=161	-1.42 (9.609)

Adverse Events

Time Frame	All cause mortality, non-serious TEAEs and serious TEAEs were collected up to 240 weeks from the start of the treatment.
Adverse Event Reporting Description	Safety analysis population was used to collect the adverse events
Arm/Group Title	Tenofovir Disoproxil Fumarate 300 mg
Arm/Group Description	Participants received Tenofovir Disoproxil Fumarate 300 mg tablet once daily (QD) orally for 240 weeks.
All Cause Mortality
	Tenofovir Disoproxil Fumarate 300 mg
	Affected / at Risk (%)	# Events
Total	2/195 (1%)
Serious Adverse Events
	Tenofovir Disoproxil Fumarate 300 mg
	Affected / at Risk (%)	# Events
Total	34/195 (17.4%)
Blood and lymphatic system disorders
Hypersplenism	1/195 (0.5%)
Cardiac disorders
Rheumatic heart disease	1/195 (0.5%)
Ear and labyrinth disorders
Vertigo positional	1/195 (0.5%)
Gastrointestinal disorders
Chronic gastritis	1/195 (0.5%)
Hepatobiliary disorders
Bile duct stone	1/195 (0.5%)
Cholelithiasis	2/195 (1%)
Cholecystitis	1/195 (0.5%)
Cholecystitis acute	1/195 (0.5%)
Hepatic cirrhosis	1/195 (0.5%)
Infections and infestations
Pneumonia	1/195 (0.5%)
Upper respiratory tract infection	1/195 (0.5%)
Injury, poisoning and procedural complications
Foot fracture	1/195 (0.5%)
Lower limb fracture	1/195 (0.5%)
Post procedural bile leak	1/195 (0.5%)
Radius fracture	1/195 (0.5%)
Spinal compression fracture	1/195 (0.5%)
Tibia fracture	1/195 (0.5%)
Investigations
Chest X-ray abnormal	1/195 (0.5%)
Musculoskeletal and connective tissue disorders
Rheumatic fever	1/195 (0.5%)
Synovial cyst	1/195 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	13/195 (6.7%)
Malignant melanoma	1/195 (0.5%)
Ovarian germ cell teratoma	1/195 (0.5%)
Renal and urinary disorders
Ureterolithiasis	1/195 (0.5%)
Reproductive system and breast disorders
Uterine adhesions	1/195 (0.5%)
Respiratory, thoracic and mediastinal disorders
Nasal polyps	1/195 (0.5%)
Nasal septum deviation	1/195 (0.5%)
Rhinitis hypertrophic	1/195 (0.5%)
Skin and subcutaneous tissue disorders
Urticaria	1/195 (0.5%)
Other (Not Including Serious) Adverse Events
	Tenofovir Disoproxil Fumarate 300 mg
	Affected / at Risk (%)	# Events
Total	129/195 (66.2%)
Blood and lymphatic system disorders
Anaemia	9/195 (4.6%)
Iron deficiency anaemia	2/195 (1%)
Thrombocytopenia	2/195 (1%)
Splenomegaly	1/195 (0.5%)
Coagulopathy	1/195 (0.5%)
Leukopenia	1/195 (0.5%)
Cardiac disorders
Bradycardia	1/195 (0.5%)
Ear and labyrinth disorders
Tinnitus	1/195 (0.5%)
Eye disorders
Vitreous floaters	1/195 (0.5%)
Retinal vein occlusion	1/195 (0.5%)
Gastrointestinal disorders
Ascites	6/195 (3.1%)
Toothache	5/195 (2.6%)
Diarrhoea	4/195 (2.1%)
Abdominal pain	3/195 (1.5%)
Abdominal pain upper	3/195 (1.5%)
Gastritis	2/195 (1%)
Dyspepsia	2/195 (1%)
Epigastric discomfort	2/195 (1%)
Abdominal distension	2/195 (1%)
Gastric ulcer	2/195 (1%)
Flatulence	2/195 (1%)
Chronic gastritis	2/195 (1%)
Nausea	2/195 (1%)
Haemorrhoidal haemorrhage	1/195 (0.5%)
Gastrointestinal pain	1/195 (0.5%)
Abdominal mass	1/195 (0.5%)
Dysbacteriosis	1/195 (0.5%)
Abdominal discomfort	1/195 (0.5%)
Duodenitis	1/195 (0.5%)
Dental caries	1/195 (0.5%)
Constipation	1/195 (0.5%)
Colitis	1/195 (0.5%)
Haemorrhoids thrombosed	1/195 (0.5%)
Vomiting	1/195 (0.5%)
Intestinal polyp	1/195 (0.5%)
General disorders
Pyrexia	1/195 (0.5%)
Fatigue	1/195 (0.5%)
Chest pain	1/195 (0.5%)
Hepatobiliary disorders
Cholelithiasis	5/195 (2.6%)
Hepatic pain	2/195 (1%)
Liver injury	2/195 (1%)
Hyperbilirubinaemia	2/195 (1%)
Cholecystitis	2/195 (1%)
Hepatic steatosis	1/195 (0.5%)
Hepatic function abnormal	1/195 (0.5%)
Gallbladder polyp	1/195 (0.5%)
Immune system disorders
Hypersensitivity	1/195 (0.5%)
Infections and infestations
Upper respiratory tract infection	36/195 (18.5%)
Urinary tract infection	11/195 (5.6%)
Nasopharyngitis	3/195 (1.5%)
Pharyngitis	2/195 (1%)
Pneumonia	2/195 (1%)
Pulmonary tuberculosis	2/195 (1%)
Urethritis	1/195 (0.5%)
Vulvovaginal mycotic infection	1/195 (0.5%)
Rhinitis	1/195 (0.5%)
Myringitis	1/195 (0.5%)
Herpes virus infection	1/195 (0.5%)
Tonsillitis bacterial	1/195 (0.5%)
Vaginal infection	1/195 (0.5%)
Injury, poisoning and procedural complications
Animal bite	2/195 (1%)
Ligament sprain	2/195 (1%)
Joint injury	1/195 (0.5%)
Ligament injury	1/195 (0.5%)
Thermal burn	1/195 (0.5%)
Skin wound	1/195 (0.5%)
Investigations
Blood creatine phosphokinase increased	9/195 (4.6%)
Protein urine present	4/195 (2.1%)
Blood phosphorus decreased	3/195 (1.5%)
Alpha 1 foetoprotein increased	3/195 (1.5%)
Blood urine present	2/195 (1%)
Weight decreased	2/195 (1%)
Blood uric acid increased	2/195 (1%)
Blood glucose increased	1/195 (0.5%)
White blood cell count decreased	1/195 (0.5%)
Red blood cells urine positive	1/195 (0.5%)
Platelet count decreased	1/195 (0.5%)
Neutrophil count decreased	1/195 (0.5%)
Hepatitis B DNA increased	1/195 (0.5%)
Glomerular filtration rate decreased	1/195 (0.5%)
Gamma-glutamyltransferase increased	1/195 (0.5%)
Creatinine renal clearance decreased	1/195 (0.5%)
Blood urine	1/195 (0.5%)
Blood lactate dehydrogenase increased	1/195 (0.5%)
Aspartate aminotransferase increased	1/195 (0.5%)
Alanine aminotransferase increased	1/195 (0.5%)
Transaminases increased	3/195 (1.5%)
Metabolism and nutrition disorders
Hypophosphataemia	15/195 (7.7%)
Hypocalcaemia	7/195 (3.6%)
Hyperglycaemia	2/195 (1%)
Hyperuricaemia	1/195 (0.5%)
Hypermagnesaemia	1/195 (0.5%)
Diabetes mellitus	1/195 (0.5%)
Hypokalaemia	3/195 (1.5%)
Musculoskeletal and connective tissue disorders
Back pain	4/195 (2.1%)
Pain in extremity	2/195 (1%)
Osteoporosis	2/195 (1%)
Spinal osteoarthritis	1/195 (0.5%)
Musculoskeletal pain	1/195 (0.5%)
Intervertebral disc protrusion	1/195 (0.5%)
Arthralgia	1/195 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	1/195 (0.5%)
Uterine leiomyoma	1/195 (0.5%)
Nervous system disorders
Dizziness	2/195 (1%)
Migraine	1/195 (0.5%)
Headache	1/195 (0.5%)
Hypoaesthesia	1/195 (0.5%)
Psychiatric disorders
Sleep disorder	1/195 (0.5%)
Depression	1/195 (0.5%)
Insomnia	1/195 (0.5%)
Renal and urinary disorders
Nephrolithiasis	3/195 (1.5%)
Renal impairment	3/195 (1.5%)
Proteinuria	2/195 (1%)
Haematuria	1/195 (0.5%)
Renal injury	1/195 (0.5%)
Renal cyst	1/195 (0.5%)
Hypertonic bladder	1/195 (0.5%)
Reproductive system and breast disorders
Menstruation irregular	2/195 (1%)
Uterine enlargement	1/195 (0.5%)
Pelvic fluid collection	1/195 (0.5%)
Breast hyperplasia	1/195 (0.5%)
Menstruation delayed	1/195 (0.5%)
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	3/195 (1.5%)
Cough	2/195 (1%)
Nasal dryness	1/195 (0.5%)
Oropharyngeal pain	1/195 (0.5%)
Nasal obstruction	1/195 (0.5%)
Skin and subcutaneous tissue disorders
Rash	3/195 (1.5%)
Psoriasis	1/195 (0.5%)
Pruritus	1/195 (0.5%)
Leukoderma	1/195 (0.5%)
Eczema	1/195 (0.5%)
Vascular disorders
Hypertension	5/195 (2.6%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.