Clinical trial NCT00441974: Adefovir Dipivoxil For The Treatment Of Chinese Compensated Chronic Hepatitis B(CHB)Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: adefovir dipivoxil
compensated
chronic hepatitis B
Chinese
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-03-01
Enrollment: 1470
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects aged 18-65 years inclusive
* Documented chronic hepatitis B infection determined by the presence of serum HBsAg for a least 6 months
* Serum HBV DNA ≥105 copies/ml for HBeAg positive subjects or ≥104 copies/ml for HBeAg negative subjects (Real-time PCR, LLQ=1000cp/ml) at study screening (within 2 weeks before baseline), respectively.
* ALT value ≥2 times the upper limit of normal (ULN) at the time of screening, as determined using laboratory ranges and documented ALT abnormal within 6 month prior the study screening.
* Compensated liver disease with the following laboratory and clinical parameters study screening:
* prothrombin time ≤ 2 seconds above normal direct bilirubin
* Albumin≥35g/L
* Total bilirubin ≤2.5mg/dL (≤ 43 µmol/L) or normal direct bilirubin
* No history of variceal bleeding
* No history of encephalopathy
* No history of ascites
* Willing and able to undergo two liver biopsies (prior to dosing, and after 48 weeks of therapy; only apply to subjects who are enrolled to the sites where liver biopsy is required).
* Agree not to participate in any other investigational trials or to undertake other HBV systemic antiviral regimens during participation in this study

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

* Any serious or active medical or psychiatric illnesses other than hepatitis B which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol. This would include, may not limit to, renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, active infection or cancer.
* Documented evidence of active liver disease due to other causes including
* co-infection hepatitis C (HCV), Subjects who are anti-HCV positive and in whom HCV RNA is undetectable are considered to be HCV seropositive and will not be eligible
* co-infection with hepatitis delta (HDV)
* co-infection with HIV
* autoimmune hepatitis (antinuclear antibody titre\>1:160)
* Alanine aminotransferase(ALT) \> 10 times ULN at screening or history of acute exacerbation leading to transient decompensation
* Serum alpha fetoprotein (AFP) \>50 ng/mL.
* Hepatocellular carcinoma as evidenced by one of the following:
* suspicious foci on ultrasound or radiological examination
* where no positive ultrasound finding, but serum alpha-fetoprotein \> 100ng/ml
* Adequate renal function defined as serum creatinine \>1.5 mg/dL (\>130 µmol/L)
* Adequate hematological function defined as:
* Absolute neutrophil count \<1 x 10³/mm³ (1 x 10\^9/L)
* Platelets\<80 x 10³/mm³ (80 x 10\^9/L); platelets\<100 x 10³/mm³ (100 x 10\^9/L)
* Hemoglobin\<12g/dL (120 g/L)(males) or \<10 g/dL (100 g/L) (females)
* Active alcohol or drug abuse or history of alcohol or drug abuse considered by the investigator to be sufficient to hinder compliance with treatment, participation in the study or interpretation of results.
* Use of immunosuppressive therapy, immunomodulatory therapy (including interferon or thymosin), systemic cytotoxic agents within the previous 6 months or during the study.
* Use of chronic anti-viral agents(e.g. lamivudine, adefovir dipivoxil, entecavir, famciclovir, tenofovir, FTC, ganciclovir, DAPD, LfMA, HBIg, etc.), Chinese herbal medicines known to have activity against HBV within the previous 3 months or during the study; use of agents with effect of ALT reduction (e.g. schisandra agents) during the study.
* Received nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal excretion (e.g., probenecid within 2 months prior to study screening or the expectation that patient will receive any of these during the course of the study.
* Received hepatotoxic drugs (e.g., anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin) within 2 months prior to study screening or expected to receive these during the course of the study.
* Previous (or planned) participation in an investigational trial involving administration of investigational compound within 2 months prior to the study screening.

Primary outcomes:
measure: Number of Participants Achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 Copies/Milliliter at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Number of HBeAg Positive Participants Achieving Histological Improvement at Week 48
timeFrame: Week 48
measure: Ranked Assessment of Liver Histology in HBeAg Positive Participants From Baseline to Week 48
timeFrame: Baseline to Week 48
measure: Change From Screening in Median Serum HBV DNA at Weeks 24 and 48
timeFrame: Weeks 24 and 48
measure: Number of Participants Achieving ALT (Alanine Aminotransferase) Normalization at Week 48
timeFrame: Week 48
measure: Number of HBeAg Positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Week 48
timeFrame: Week 48
measure: Number of Participants With ADV-associated Resistance at Week 48
timeFrame: Week 48
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Wuhan
country: China
facility: GSK Investigational Site
state: Hubei
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Changchun
country: China
facility: GSK Investigational Site
state: Jilin
city: Chengdu
country: China
facility: GSK Investigational Site
state: Sichuan
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: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Changsha
country: China
facility: GSK Investigational Site
city: Changsha
country: China
facility: GSK Investigational Site
city: Chongqing
country: China
facility: GSK Investigational Site
city: Chongquin
country: China
facility: GSK Investigational Site
city: Fuzhou
country: China
facility: GSK Investigational Site
city: Jinan
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Tianjin
country: China
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: