Clinical trial NCT00338780: Trial of Lamivudine Treatment in HBeAg Negative Chronic Hepatitis B Patients (in Asia)
Official title: A Randomised, Double-Blinded, Placebo-Controlled Trial of Lamivudine Treatment in HBeAg Negative Chronic Hepatitis B Patients (in Asia)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: Chronic Hepatitis B
Lamivudine
HBeAg negative
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2006-06-20
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 aim is to investigate whether Lamivudine 100mg daily is effective in the long term treatment of HBeAg negative chronic HBV infected patients with active liver disease in Asia

Detailed description: Recent studies have proved lamivudine a very potent antiviral drug in suppressing viral replication and improving hepatic necro-inflammation with minimal adverse effects in HBeAg positive chronic hepatitis B patients. The efficacy of lamivudine in HBeAg positivce Asian patients has been weel established. However, the evidence in HBeAg negative patients is limited.

In the absence of HBeAg seroconversion, guidance on the clinical management of HBeAg negative hepatitis B patitents treated with lamivudine and data on the efficacy of lamivudine in controlling pre-core HBV disease long-term is still needed. Existing data in HBeAg negative/ HBV DNA positive HBV demonstrate clear and statisticallysignificant serological benefit of lamivudine over placebo during treatment. Limited sustained response was observed post-treatment following a one year treatment period. Whether these results can be applied to patients in Asia is uncertain. This study is therefore intended to further assess te efficacy profile over an extended treatment period in the Asian population.

Eligibility criteria: Inclusion Criteria:

* Age=\>18 years
* HBsAg positive and HBeAg negative for at least 6 months prior to screening
* Serum HBV-DNA postiviet, HBeAg negative and HBeAb positive at the same timepoint on at least one occasion during the last 6 months
* ALT \>1.5 to 10 x upper limit of normal for at least two occasions within the previous 6 months and at screening, or ALT \> upper limit normal and with at least one biochemical flare-up (ALT \> 200IU/l) in the last 12 months.
* Informed writted consent
* Liver biopsy material/ slides taken within the previous 12 months, and at least 5 months after any previous antiviral treatment which show evidence of active liver disease (ie. evidence of necroinflammatory activity)
* Written informed consent

Exclusion Criteria:

* Hepatocellular carcinoma
* ALT \> 10xULN at screening or history of acute exacerbation leading to transient decompensation
* Serum hepatitis C, hepatitis D or HIV
* Decompensated liver desease as indicated by any of the following: serum bilirubin \>3mg/dL, prothrombin time \>=2 seconds prolonged above upper limit of reference range, serum albumin \<28g/L, history of variceal haemorrhage, presence of intractable ascites at the screening assessment.
* Encepalopathy
* Planned for liver transplantation or previous liver transplantation
* Evidence of autoimmune hepatitis
* Amylase and/ or lipase \> 2 times upper limit of reference range
* Serum creatinine \>1.5 times upper limit of reference range
* Haemoglobin \< 11g/dL
* WBC count \<3x10\^9/L
* Platelets \<100x10\^9
* Serious concurrent medical illness other than hepatitis B
* Use of immunosuppressive therapy, immunomodylatory therapy or chronic antiviral thgerpay with other agents within the previous 6 months or during the study
* Previous treatment with lamivudine or famciclovir within the last 6 months
* History of hypersensitivity to nucleoside analogues
* Women of childbearing potential not practising adequate contraception
* Pregnancy or lactation
* Receipt of any investigational drug within 30 days of the first dose of study drug
* Child-Pugh class B or C cirrhosis

Primary outcomes:
measure: Proportion of patients with complete response (normalisation of LAT, ie. <1xULN and disappearance of HBV DNA, lower limit of detection), at MOnth 24
Secondary outcomes:
measure: Proportion of patients with partial response
measure: Histological improvement at month 24
measure: Proportion of patients with complete response post-treatment (at Month 30)
measure: Proportion of patinets with partial response post-treatment (at Month 30)
measure: Progression of fibrosis
measure: Progression of fibrosis to cirrhosis
measure: HBsAg seroconversion
measure: Safety of treatment
Other outcomes:
Locations:
city: Hong Kong SAR
country: China
facility: Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Joseph JY Sung, PhD
role: PRINCIPAL_INVESTIGATOR
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