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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT00338780
First received: June 19, 2006
Last updated: October 27, 2006
Last verified: October 2006
History of Changes
  Purpose

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


Condition Intervention Phase
Chronic Hepatitis B
 Drug: Lamivudine/ Placebo 100mg daily
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomised, Double-Blinded, Placebo-Controlled Trial of Lamivudine Treatment in HBeAg Negative Chronic Hepatitis B Patients (in Asia)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • Proportion of patients with complete response (normalisation of LAT, ie. <1xULN and disappearance of HBV DNA, lower limit of detection), at MOnth 24

Secondary Outcome Measures:
  • Proportion of patients with partial response
  • Histological improvement at month 24
  • Proportion of patients with complete response post-treatment (at Month 30)
  • Proportion of patinets with partial response post-treatment (at Month 30)
  • Progression of fibrosis
  • Progression of fibrosis to cirrhosis
  • HBsAg seroconversion
  • Safety of treatment

Study Start Date: November 2000
Estimated Study Completion Date: January 2005
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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00338780

Locations
China
Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital
Hong Kong SAR, China
Sponsors and Collaborators
Chinese University of Hong Kong
GlaxoSmithKline
Investigators
Principal Investigator: Joseph JY Sung, PhD Chinese University of Hong Kong
  More Information

Publications:
Chan HLY, Hui Y, Ching JYL, Leung NWY, Chan FKL, Sung JJY. Can we predict disease activity in chronic hepatitis B virus (CHB) infected patients with negative HBeAg. Gastroenterology 1999; 116: A1195
Chan HLY,Ghany MC, Lok ASF. Hepatitis B. In Schiff ER, Sorrell MF, Madrey WC, Eds. Schiff's Deseases of the LIver, 8th ed. Lippincott-Raven Publishers, New York, 1998:757-92

ClinicalTrials.gov Identifier: NCT00338780     History of Changes
Other Study ID Numbers: NUC30934
Study First Received: June 19, 2006
Last Updated: October 27, 2006
Health Authority: Hong Kong: Department of Health

Keywords provided by Chinese University of Hong Kong:
Chronic Hepatitis B
Lamivudine
HBeAg negative

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
 DNA Virus Infections
Lamivudine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 19, 2013