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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation N236T

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 6 clinical trials

Clinical Trials


1 A 48-week Multi-centre, Open-label, Local Phase IV Study to Demonstrate the Efficacy and Safety of Adefovir Dipivoxil Tablets (10mg) in Chinese Subjects With Compensated Chronic Hepatitis B

This 48-week open-label study of local manufactured adefovir dipivoxil Tablet evaluates the efficacy and safety of adefovir 10mg once daily in Chinese subjects with compensated CHB. Primary endpoint is proportion of subjects achieving HBV DNA undetectable (<=1000 copies/mL by by Roche COBAS AMPLICOR HBV MONITOR Test) at week 48. Approximately 1250 patients will be recruited in 30 study centers in China. The subjects are offered 48 weeks of open label adefovir dipivoxil treatment, with assessments every three months, after with is a 12-week post study treatment follow-up prior to study completion.

NCT00441974
Conditions
  1. Chronic Hepatitis B
Interventions
  1. Drug: adefovir dipivoxil
MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

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. --- N236T ---

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

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

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

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

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

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

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

2 A Multi-Centre, Double-Blind , Randomized, Placebo-Controlled Phase II/III Study of Adefovir Dipivoxil for the Treatment of Chinese Patients With HBeAg Positive Chronic Hepatitis B Followed by Long-Term (5 Years Total) Adefovir Dipivoxil Treatment. (Report on Year 1 and Year 2 Data)

The purpose of this study is to determine whether Adefovir Dipivoxil is effective and safe in treatment of Chinese Patients with HBeAg positive Chronic Hepatitis B for 5 years.

NCT00857675
Conditions
  1. Chronic Hepatitis B
Interventions
  1. Drug: AAAA
  2. Drug: AAPA
  3. Drug: PAAA
MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

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

Primary Outcomes

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

Time: Week 12

Secondary Outcomes

Measure: The proportion of subjects with ALT normalisation

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

Measure: log10 reduction in serum HBV DNA

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

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

Measure: The proportion of subjects with HBeAg loss

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

Measure: The proportion of subjects with HBeAg seroconversion

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

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

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

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

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

3 Clinical Trial of Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic HBV Infection (HBRN)

The purpose of this study is to determine the safety and efficacy of treatment using a combination of drugs (entecavir and pegylated interferon) in children ages 3-<18 years old with immunotolerant chronic hepatitis B.

NCT01368497
Conditions
  1. Hepatitis B
Interventions
  1. Drug: Entecavir and peginterferon
MeSH:Hepatitis A Hepatitis B Hepatitis
HPO:Hepatitis

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.. Growth Measures: Z-scores Weight, Height, and Body Mass Index. --- L82M --- --- T128N --- --- W153Q --- --- F166L --- --- I169T --- --- V173L --- --- L180M --- --- V191T --- --- A194T --- --- A200V --- --- V207I --- --- N236T ---

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)

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)

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)

Secondary Outcomes

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

Time: End of treatment (up to 48 weeks)

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

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

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

Time: End of treatment (up to 48 weeks)

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

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

Measure: Proportion of Participants With HBeAg Seroconversion

Time: End of treatment (up to 48 weeks)

Measure: Proportion of Participants With HBeAg Seroconversion

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

Measure: Proportion of Participants With HBsAg Seroconversion

Time: End of treatment (up to 48 weeks)

Measure: Proportion of Participants With HBsAg Seroconversion

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

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)

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)

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

Time: End of treatment (up to 48 weeks)

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

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

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

Time: End of treatment (up to 48 weeks)

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

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

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)

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)

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)

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)

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)

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)

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)

4 Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B

The investigators evaluated the safety and efficacy of a short lead-in course (8 weeks) of entecavir followed by combination of entecavir plus peginterferon alfa-2a for 40 weeks.

NCT01369199
Conditions
  1. Hepatitis B
Interventions
  1. Drug: Entecavir and peginterferon
MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis
HPO:Hepatitis

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.. Inclusion Criteria: - Enrolled in & completed the baseline evaluation for NCT01263587 or completed the necessary components of NCT01263587 by the end of baseline visit. --- L82M --- --- T128N --- --- W153Q --- --- F166L --- --- I169T --- --- V173L --- --- L180M --- --- V191T --- --- A194T --- --- A200V --- --- V207I --- --- N236T ---

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)

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)

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)

Secondary Outcomes

Measure: Proportion of Participants With HBeAg Loss

Time: End of treatment (up to 48 weeks)

Measure: Proportion of Participants With HBeAg Loss

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

Measure: Proportion of Participants With HBeAg Seroconversion

Time: End of treatment (up to 48 weeks)

Measure: Proportion of Participants With HBeAg Seroconversion

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

Measure: Proportion of Participants With HBsAg Loss

Time: End of treatment (up to 48 weeks)

Measure: Proportion of Participants With HBsAg Loss

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

Measure: Proportion of Participants With HBsAg Seroconversion

Time: End of treatment (up to 48 weeks)

Measure: Proportion of Participants With HBsAg Seroconversion

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

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)

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)

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

Time: End of treatment (up to 48 weeks)

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

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

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

Time: End of treatment (up to 48 weeks)

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

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

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

Time: End of treatment (up to 48 weeks)

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

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

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)

5 A Two-year, Randomized, Controlled, Open-label, Virologic Response Adaptive Design, Multicenter Study to Optimize Antiviral Efficacy of Telbivudine in Adult Patients With HBeAg Positive Chronic Hepatitis B (EFFORT Study)

The purpose of this trial is to prove that the strategy of treatment adjustment at W24 according to virological response based on ROADMAP concept is better than standard of care strategy.

NCT00962533
Conditions
  1. Hepatitis B, Chronic
Interventions
  1. Drug: telbivudine
  2. Drug: telbivudine
MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis
HPO:Hepatitis

Inclusion Criteria: - Male or female, from 18 (inclusive) to 65 (inclusive) years of age - HBsAg and HBeAg positive for over six months - Patient is willing and able to comply with the study drug regimen and all other study requirements - Patients must give written informed consent before any assessment is performed Exclusion Criteria: - Detected M204I/V, N236T, A181V/T mutation in patient serum HBV DNA at Screening visit - Patient has a history of or clinical signs/symptoms of hepatic decompensation - Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC - Other protocol-defined inclusion/exclusion criteria may apply Inclusion Criteria: - Male or female, from 18 (inclusive) to 65 (inclusive) years of age - HBsAg and HBeAg positive for over six months - Patient is willing and able to comply with the study drug regimen and all other study requirements - Patients must give written informed consent before any assessment is performed Exclusion Criteria: - Detected M204I/V, N236T, A181V/T mutation in patient serum HBV DNA at Screening visit - Patient has a history of or clinical signs/symptoms of hepatic decompensation - Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC - Other protocol-defined inclusion/exclusion criteria may apply Hepatitis B, Chronic Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis null --- M204I --- --- N236T ---

Inclusion Criteria: - Male or female, from 18 (inclusive) to 65 (inclusive) years of age - HBsAg and HBeAg positive for over six months - Patient is willing and able to comply with the study drug regimen and all other study requirements - Patients must give written informed consent before any assessment is performed Exclusion Criteria: - Detected M204I/V, N236T, A181V/T mutation in patient serum HBV DNA at Screening visit - Patient has a history of or clinical signs/symptoms of hepatic decompensation - Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC - Other protocol-defined inclusion/exclusion criteria may apply Inclusion Criteria: - Male or female, from 18 (inclusive) to 65 (inclusive) years of age - HBsAg and HBeAg positive for over six months - Patient is willing and able to comply with the study drug regimen and all other study requirements - Patients must give written informed consent before any assessment is performed Exclusion Criteria: - Detected M204I/V, N236T, A181V/T mutation in patient serum HBV DNA at Screening visit - Patient has a history of or clinical signs/symptoms of hepatic decompensation - Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC - Other protocol-defined inclusion/exclusion criteria may apply Hepatitis B, Chronic Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis null --- M204I --- --- N236T --- --- A181V --- --- M204I --- --- N236T ---

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

Secondary Outcomes

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

Time: week 52

Measure: Serum HBV DNA reduction from baseline at week 104

Time: week 104

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

Time: week 104

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

Measure: Serum HBV DNA reduction from baseline at week 52

Time: week 52

6 A 2-year Multi-centre, Open-label, Local Phase IV Study to Demonstrate the Efficacy and Safety of Adefovir Dipivoxil Tablets (10mg) in Chinese Subjects With HBe Antigen Negative Chronic Hepatitis B

This is a phase IV, 2-year, multi-center, single arm and open-label study, evaluating the efficacy and safety with using local manufactured adefovir dipivoxil in Chinese subjects with HBeAg negative chronic hepatitis B

NCT00324961
Conditions
  1. Chronic Hepatitis B
Interventions
  1. Drug: adefovir dipivoxil tablets
MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

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. --- N236T ---

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

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

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

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

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

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

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

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

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

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


HPO Nodes