Primary Outcomes

Description: HBV (Hepatitis B Virus) DNA level was tested by real-time Polymerase Chain Reaction at Week 48.

Measure: Number of Participants Achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 Copies/Milliliter at Week 48

Time: Week 48

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Secondary Outcomes

Description: Histological improvement (defined as a ≥2 point reduction in the Knodell necroinflammation score without worsening fibrosis) was accessed by two pathologists in HBeAg-positive participants undergoing liver biopsy at baseline and week 48/withdrawal. Knodell/Histological Activity Index (HAI) score = combined scores for necrosis, inflammation, and fibrosis and is the sum of scores for periportal bridging necrosis (0-10: none=0, multilobular necrosis=10), intralobular degeneration and focal necrosis and portal inflammation (0-4: none=0, marked=4), and fibrosis (0-4: none=0, cirrhosis=4).

Measure: Number of HBeAg Positive Participants Achieving Histological Improvement at Week 48

Time: Week 48

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Description: A ranked assessment with the Knodell/HAI scoring system that represents the sum of scores for periportal bridging necrosis (0-10: none=0, moderate piecemeal necrosis plus bridging necrosis=5, multilobular necrosis=10); interlobular degeneration and focal necrosis (0-4: none=0, marked=4); portal inflammation (0-4: none=0, marked=4) and fibrosis (0-4: none=0, fibrous portal expansion=1, bridging fibrosis=3, cirrhosis=4) was carried out by two pathologists in the HBeAg positive participants who underwent liver biopsy at baseline and Week 48/withdrawal.

Measure: Ranked Assessment of Liver Histology in HBeAg Positive Participants From Baseline to Week 48

Time: Baseline to Week 48

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Description: The HBV DNA level was tested in blood serum by real-time Polymerase Chain Reaction with the LLD (lower limit of detection) as 300 copies/milliliter (cp/mL) at screening, week 24, and week 48 in a central laboratory. The change in HBV DNA from screening to week 24 and week 48 was conducted.

Measure: Change From Screening in Median Serum HBV DNA at Weeks 24 and 48

Time: Weeks 24 and 48

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Description: Elevated serum ALT levels are defined as serum ALT levels greater than the upper limit of the normal range (ULN), as determined using local laboratory ranges. ALT normalization was defined as ALT measurements at or below the ULN after a baseline value above the ULN.

Measure: Number of Participants Achieving ALT (Alanine Aminotransferase) Normalization at Week 48

Time: Week 48

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Description: HBeAg loss and HBeAg seroconversion (HBeAg loss and HBeAb detected) were assessed in participants who were HBeAg positive at Weeks 0 and 48. Confirmed HBeAg loss was defined as undetectable HBeAg.

Measure: Number of HBeAg Positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Week 48

Time: Week 48

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Description: Week 48 serum samples from participants, who reached a HBV DNA breakthrough or have HBV DNA≥5 log copies/mL at Weeks 24 and 48 were assessed for the development of ADV (Adefovir dipivoxil) mutation (N236T and A181V) in the HBV polymerase. Virologic breakthrough was defined as an increase in the level of HBV DNA 1 log10 copy/mL from Week 24 to Week 48. ADV-associated resistance was defined as participants with both virologic breakthrough and ADV mutation.

Measure: Number of Participants With ADV-associated Resistance at Week 48

Time: Week 48

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Primary Outcomes

Measure: The log10 reduction in HBV DNA from baseline at week 12 between ADV 10mg and matching placebo

Time: Week 12

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Secondary Outcomes

Measure: The proportion of subjects with ALT normalisation

Time: Week 52, 104, 156, 208, 260

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Measure: log10 reduction in serum HBV DNA

Time: Week 52, 104, 156, 208, 260

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Measure: The proportion of subjects with HBV DNA 10(5) copies/mL or a 2 log10 reduction from Baseline HBV DNA level

Time: Week 52, 104, 156, 208, 260

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Measure: The proportion of subjects with HBeAg loss

Time: Week 52, 104, 156, 208, 260

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Measure: The proportion of subjects with HBeAg seroconversion

Time: Week 52, 104, 156, 208, 260

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Measure: The proportion of subjects developing N236T and A181V HBV DNA genotypic mutations associated with ADV resistance

Time: Week 52, 104, 156, 208, 260

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Measure: The proportion of subjects with HBV DNA undetectable (<300 copies/mL)

Time: Week 52, 104, 156, 208, 260

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Primary Outcomes

Measure: Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss & Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels ≤1,000 International Units (IU) Per Milliliter (mL)

Time: End of follow-up (up to 96 weeks)

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Description: The number of AEs includes both AEs and Serious Adverse Events (SAEs). The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.

Measure: Incidence of Adverse Events (AEs) Per Person-Year

Time: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)

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Description: The incidence is calculated as the number of SAEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.

Measure: Incidence of Serious Adverse Events (SAEs) Per Person-Year

Time: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)

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Secondary Outcomes

Measure: Proportion of Participants With Hepatitis B Surface Antigen (HBsAg) Loss

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With Hepatitis B Surface Antigen (HBsAg) Loss

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBeAg Seroconversion

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBeAg Seroconversion

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBsAg Seroconversion

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBsAg Seroconversion

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With Alanine Aminotransferase (ALT) ≤ 40 Units (U) Per Liter (L) for Males, ≤ 35 U/L for Females

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With ALT ≤ 40 U/L for Males, ≤ 35 U/L for Females

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBV DNA ≤1000 IU/mL

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBV DNA ≤1000 IU/mL

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBV DNA < 20 IU/mL

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBV DNA < 20 IU/mL

Time: End of follow-up (up to 96 weeks)

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Description: HBV drug resistance variant testing was performed at the CDC laboratory. The sequences of the HBV polymerase spanning nucleotide positions 311-1021 were determined by Sanger sequencing. Drug resistance mutations that were tested in this study included L80VI, L82M, T128N, W153Q, F166L, I169T, V173L, L180M, A181TV, T184ACFGILMS, V191T, A194T, A200V, S202ETV, M204IV, V207I, N236T, M250ILV, and G145R.

Measure: Proportion Without Detectable Antiviral Drug-resistance HBV Mutations

Time: End of treatment (up to 48 weeks)

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Description: A child's Z-score is the number of standard deviations that the child is from the average of children of the same sex and age from a reference population. The reference population is provided in the 2000 Centers for Disease Control and Prevention (CDC) growth charts. Positive Z scores mean the growth measure (weight, height, or body mass index) is above the average, negative Z scores mean the growth measure is below the average.

Measure: Growth Measures: Z-scores Weight, Height, and Body Mass Index

Time: End of treatment (up to 48 weeks)

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Description: A child's Z-score is the number of standard deviations that the child is from the average of children of the same sex and age from a reference population. The reference population is provided in the 2000 Centers for Disease Control and Prevention (CDC) growth charts. Positive Z scores mean the growth measure (weight, height, or body mass index) is above the average, negative Z scores mean the growth measure is below the average.

Measure: Growth Measures: Z-scores Weight, Height, and Body Mass Index

Time: End of follow-up (up to 96 weeks)

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Description: The Tanner Stage questionnaire is only completed by participants 8 years of age and older. The copyrighted form includes pictures and descriptions. Girls selected the picture closest to their self-perceived breast growth from among 5 stages of breast growth and boys did the same for testes, scrotum, and penis growth. Boys: I-prepubertal; II-enlargement of scrotum and testes; III-enlargement of the penis and further growth of testes; IV- increased size of penis with growth in breadth and development of glans, testes, and scrotum larger, scrotum skin darker; V- adult genitalia. Girls: I-prepubertal; II-breast bud stage with the elevation of breast and papilla and enlargement of the areola; III-further enlargement of breast and areola, no separation of their contour; IV-areola and papilla form a secondary mound above the level of the breast; V: mature adult stage. There is no "better" or "worse" outcome. They are self-assessed descriptive measures of physical growth.

Measure: Tanner Stages of Physical Growth

Time: End of treatment (up to 48 weeks)

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Description: The Tanner Stage questionnaire is only completed by participants 8 years of age and older. The copyrighted form includes pictures and descriptions. Girls selected the picture closest to their self-perceived breast growth from among 5 stages of breast growth and boys did the same for testes, scrotum, and penis growth. Boys: I-prepubertal; II-enlargement of scrotum and testes; III-enlargement of the penis and further growth of testes; IV- increased size of penis with growth in breadth and development of glans, testes, and scrotum larger, scrotum skin darker; V- adult genitalia. Girls: I-prepubertal; II-breast bud stage with the elevation of breast and papilla and enlargement of the areola; III-further enlargement of breast and areola, no separation of their contour; IV-areola and papilla form a secondary mound above the level of the breast; V: mature adult stage. There is no "better" or "worse" outcome. They are self-assessed descriptive measures of physical growth.

Measure: Tanner Stages of Physical Growth

Time: End of follow-up (up to 96 weeks)

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Description: The Tanner Stage questionnaire is only completed by participants 8 years of age and older. The copyrighted form includes pictures and descriptions. Participants selected the picture closest to their self-perceived pubic hair growth. Boys and girls: I-prepubertal (no pubic hair at all); II-sparse growth of long, slightly pigmented hair, straight or curled, at base of penis or along labia; III: darker, coarser and more curled hair, spreading sparsely over junction of pubes; IV- hair adult in type, but covering smaller area than in adult; V-adult in type and quantity. There is no "better" or "worse" outcome. They are self-assessed descriptive measures of physical growth.

Measure: Tanner Stages of Pubic Hair Growth

Time: End of treatment (up to 48 weeks)

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Description: The Tanner Stage questionnaire is only completed by participants 8 years of age and older. The copyrighted form includes pictures and descriptions. Participants selected the picture closest to their self-perceived pubic hair growth. Boys and girls: I-prepubertal (no pubic hair at all); II-sparse growth of long, slightly pigmented hair, straight or curled, at base of penis or along labia; III: darker, coarser and more curled hair, spreading sparsely over junction of pubes; IV- hair adult in type, but covering smaller area than in adult; V-adult in type and quantity. There is no "better" or "worse" outcome. They are self-assessed descriptive measures of physical growth.

Measure: Tanner Stages of Pubic Hair Growth

Time: End of follow-up (up to 96 weeks)

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Primary Outcomes

Description: Lack of data was considered to be treatment failure.

Measure: Proportion of Participants With HBeAg Loss (Lack of Detectable HBeAg) AND HBV DNA ≤1,000 IU/mL

Time: End of follow-up (up to 96 weeks)

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Description: The number of AEs includes both AEs and Serious Adverse Events (SAEs). The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.

Measure: Incidence of Adverse Events (AEs) Per Person-Year of Observation

Time: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)

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Description: The incidence is calculated as the number of SAEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.

Measure: Incidence of Serious Adverse Events (SAEs) Per Person-Year

Time: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)

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Secondary Outcomes

Measure: Proportion of Participants With HBeAg Loss

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBeAg Loss

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBeAg Seroconversion

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBeAg Seroconversion

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBsAg Loss

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBsAg Loss

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBsAg Seroconversion

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBsAg Seroconversion

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With Alanine Aminotransferase (ALT) <45 U/L for Men, <30 U/L for Women

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With ALT <45 U/L for Men, <30 U/L for Women

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBV DNA ≤1000 IU/mL

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBV DNA ≤1000 IU/mL

Time: End of follow-up (up to 96 weeks)

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Measure: Proportion of Participants With HBV DNA <20 IU/mL

Time: End of treatment (up to 48 weeks)

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Measure: Proportion of Participants With HBV DNA <20 IU/mL

Time: End of follow-up (up to 96 weeks)

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Description: HBV drug resistance variant testing was performed at the CDC laboratory. The sequences of the HBV polymerase spanning nucleotide positions 311-1021 were determined by Sanger sequencing. Drug resistance mutations that were tested in this study included L80VI, L82M, T128N, W153Q, F166L, I169T, V173L, L180M, A181TV, T184ACFGILMS, V191T, A194T, A200V, S202ETV, M204IV, V207I, N236T, M250ILV, and G145R.

Measure: Absence of Detectable Antiviral Drug-resistance HBV Mutations

Time: End of treatment (up to 48 weeks)

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Primary Outcomes

Measure: To demonstrate the percentage of patients achieving HBV DNA< 300copies/mL at Week 104 in Group I is superior than that in Group II

Time: Week 104

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Secondary Outcomes

Measure: Percentage of patients achieving HBV DNA <60IU/mL (300copies/mL) at Week 52

Time: week 52

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Measure: Serum HBV DNA reduction from baseline at week 104

Time: week 104

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Measure: Percentage of patients with HBeAg loss & HBeAg seroconversion at week104 in patients with HBeAg positive at baseline

Time: week 104

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Measure: Percentage of patients with HBV DNA<300copies/mL AND HBeAg loss or seroconversion at Week 104 in patients with positive HBeAg at baseline

Time: week 104

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Measure: Serum HBV DNA reduction from baseline at week 52

Time: week 52

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Primary Outcomes

Description: Hepatitis B Virus (HBV) DNA level is tested in blood serum by real-time Polymerase Chain Reaction with the lower limit of detection (LLD) as 300 copies/milliliter in a central laboratory.

Measure: Number of Participants Achieving HBV DNA ≤300 Copies/mL at Week 104

Time: Week 104

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Secondary Outcomes

Description: Histological improvement (defined as ≥2 point reduction in the Knodell necroinflammation score without worsening fibrosis) was assessed by 2 independent pathologists in the HBeAg-negative participants who underwent 2 sequential liver biopsies at baseline and week 104/withdrawal. The Knodell/histological activity index (HAI) scoring system represents the sum of scores for periportal, bridging necrosis (0-10: none=0, multilobular necrosis=10), interlobular degeneration and focal necrosis (0-4: none=0, marked=4), portal inflammation (0-4: none=0, marked=4), and fibrosis (0-4: none=0, cirrhosis=4)

Measure: Number of Participants Achieving Histological Improvement After the 104-week Treatment

Time: Week 104

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Description: The Knodell/histological activity index (HAI) scoring system that represents the sum of scores for periportal bridging necrosis (0-10: none=0, moderate piecemeal necrosis plus bridging necrosis=5, multilobular necrosis=10); interlobular degeneration and focal necrosis (0-4: none=0, marked=4); portal inflammation (0-4: none=0, marked=4) and fibrosis (0-4: none=0, fibrous portal expansion=1, bridging fibrosis=3, cirrhosis=4) was carried out by two independent pathologists in the HBeAg negative participants with 2 sequential liver biopsies during the period of 104 weeks.

Measure: Liver Histology Scores in HBeAg Negative Participants With Two Sequential Liver Biopsies During the Period of 104 Weeks

Time: Baseline to Week 104

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Description: The HBV DNA level was tested in blood serum by real-time PCR with the LLD as 300 copies/mL at baseline and Weeks 13, 26, 39, 52, 65, 78, 91, and 104 in a central laboratory.

Measure: Change From Baseline in Median Serum HBV DNA Over Time

Time: Baseline and Weeks 13, 26, 39, 52, 65, 78, 91, and 104

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Description: Serum alanine aminotransferase (ALT) normalization was defined as a serum ALT level at or below the upper limit of the normal (ULN) range after a baseline value above the ULN, as determined using central laboratory ranges.

Measure: Number of Participants Achieving ALT Normalization at Week 104

Time: Week 104

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Description: HBsAg loss and HBsAg seroconversion (HBsAg loss and HBsAb detected) were assessed for all participants who were HBeAg negative at Weeks 0 and 104. Confirmed HBsAg loss was defined as undetectable HBeAg.

Measure: Number of Participants Achieving HBsAg Loss and HBsAg Seroconversion at Week 104

Time: Week 104

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Description: Week 104 serum samples from participants who reached a HBV DNA breakthrough were assessed for the development of ADV (Adefovir dipivoxil) mutations (N236T and A181V) in the HBV polymerase. HBV DNA breakthrough was defined as an increase in HBV DNA level by 1 log10 copies/mL or more from the treatment nadir during Weeks 0 to 104.

Measure: Number of Participants With ADV-associated Resistance at Week 104

Time: Week 104

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Description: Hepatitis B Virus (HBV) DNA level is tested in blood serum by real-time Polymerase Chain Reaction with the lower limit of detection (LLD) as 300 copies/milliliter in a central laboratory.

Measure: Number of Participants Achieving HBV DNA ≤300 Copies/mL Over Time

Time: Weeks 13, 26, 39, 52, 65, 78, 91, and 104

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Description: Complete response was defined as an HBV DNA level ≤ 300 copies/mL by the Roche COBAS AMPLICOR HBV MONITOR Test and ALT normalized for two consecutive visits at least 3 months apart.

Measure: Number of Participants Achieving Complete Response at Week 104

Time: Week 104

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Description: Time to response was defined as the time to participants achieving protocol-defined complete response at week 104 from baseline. Protocol-defined complete response was an HBV DNA level ≤ 300 copies/mL by Roche COBAS AMPLICOR HBV MONITOR Test and ALT normalized for two consecutive visits at least 3 months apart.

Measure: Time to Protocol-defined Complete Response Over a 104-week Treatment Period

Time: Baseline to Week 104

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