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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
533
adefovir dipivoxil once daily 10 mg orally
GSK Investigational Site
Guangzhou, Guangdong, China
GSK Investigational Site
Guangzhou, Guangdong, China
Number of Participants Achieving HBV DNA ≤300 Copies/mL at Week 104
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.
Time frame: Week 104
Number of Participants Achieving Histological Improvement After the 104-week Treatment
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)
Time frame: Week 104
Liver Histology Scores in HBeAg Negative Participants With Two Sequential Liver Biopsies During the Period of 104 Weeks
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.
Time frame: Baseline to Week 104
Change From Baseline in Median Serum HBV DNA Over Time
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.
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GSK Investigational Site
Wuhan, Hubei, China
GSK Investigational Site
Nanjing, Jiangsu, China
GSK Investigational Site
Changchun, Jilin, China
GSK Investigational Site
Hangzhou, Zhejiang, China
GSK Investigational Site
Beijing, China
GSK Investigational Site
Beijing, China
GSK Investigational Site
Beijing, China
GSK Investigational Site
Changsha, China
...and 8 more locations
Time frame: Baseline and Weeks 13, 26, 39, 52, 65, 78, 91, and 104
Number of Participants Achieving ALT Normalization at Week 104
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.
Time frame: Week 104
Number of Participants Achieving HBsAg Loss and HBsAg Seroconversion at Week 104
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.
Time frame: Week 104
Number of Participants With ADV-associated Resistance at Week 104
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.
Time frame: Week 104
Number of Participants Achieving HBV DNA ≤300 Copies/mL Over Time
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.
Time frame: Weeks 13, 26, 39, 52, 65, 78, 91, and 104
Number of Participants Achieving Complete Response at Week 104
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.
Time frame: Week 104
Time to Protocol-defined Complete Response Over a 104-week Treatment Period
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.
Time frame: Baseline to Week 104