Clinical trial NCT00857675: A Efficacy and Safety Study of Adefovir Dipivoxil to Treat Chinese Patients With HBeAg+ve Chronic Hepatitis B
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis B
Keywords: HBV DNA suppression
ALT normalisation
Viral resistance
HBeAg seroconversion
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-03-09
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Aged 18-65 years
* Presence of HBsAg and HBeAg at the time of screening and for at least 6 months prior to screening.
* Positive HBV DNA plasma assay with screening value equal or more than 10 (6) copies/mL (Roche COBAS AMPLICORTM HBV MONITOR Test, LLOD less than 300 copies/mL) at the time of screening (within 4 weeks of randomisation).
* Evidence of elevated serum ALT levels defined as serum ALT level greater than or equal to 2.0 times (inclusive) the upper limit of the normal range (ULN) in the previous 6 months, and serum ALT levels greater than 1.0 times the ULN at the time of screening.

Exclusion Criteria:

* Evidence of hepatocellular carcinoma;
* Clinical signs of liver decompensation;
* Serum creatinine more than 1.5 mg/dL;
* ALT more than 10 x ULN; seropositivity for hepatitis C or D virus or HIV;
* Lamivudine therapy within 3 months prior to screening;
* ADV therapy or any other anti-HBV therapy within the previous 6 months;
* Use of systemic antiviral agents, immunomodulators, immunosuppressive therapy, Chinese Traditional Medicines or agents known to lower ALT levels during the study.

Primary outcomes:
measure: The log10 reduction in HBV DNA from baseline at week 12 between ADV 10mg and matching placebo
timeFrame: Week 12
Secondary outcomes:
measure: The proportion of subjects with ALT normalisation
timeFrame: Week 52, 104, 156, 208, 260
measure: log10 reduction in serum HBV DNA
timeFrame: 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
timeFrame: Week 52, 104, 156, 208, 260
measure: The proportion of subjects with HBeAg loss
timeFrame: Week 52, 104, 156, 208, 260
measure: The proportion of subjects with HBeAg seroconversion
timeFrame: Week 52, 104, 156, 208, 260
measure: The proportion of subjects developing N236T and A181V HBV DNA genotypic mutations associated with ADV resistance
timeFrame: Week 52, 104, 156, 208, 260
measure: The proportion of subjects with HBV DNA undetectable (<300 copies/mL)
timeFrame: Week 52, 104, 156, 208, 260
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Changchun
country: China
facility: GSK Investigational Site
state: Jilin
city: Jinan
country: China
facility: GSK Investigational Site
state: Shandong
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Chongqing
country: China
facility: GSK Investigational Site
city: Chongquin
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: