Trial of Lamivudine Treatment in HBeAg Negative Chronic Hepatitis B Patients (in Asia)

The Chinese University of Hong Kong

Status and phase

Completed

Phase 4

Conditions

Chronic Hepatitis B

Treatments

Drug: Lamivudine/ Placebo 100mg daily

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00338780

NUC30934

Details and patient eligibility

About

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

Full 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.

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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