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
Name: adefovir dipivoxil tablets
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 104Description: 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 104Description: 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 104Description: 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 104Description: 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 104Description: 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 104Description: 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 104Description: 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 104Description: 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 104Description: 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 104Allocation: Non-Randomized
Single Group Assignment
There are 2 SNPs
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 --- --- A181V ---
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 ---