Hepatitis B Surface Antigen(HBsAg) Loss in Chronic Hepatitis B Patients With Low Viral Load
Summary
Rationale:
Worldwide, approximately 400 million people are chronically infected with hepatitis B virus (HBV). Chronic HBV infection increases the risk of developing cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). The risk of developing hepatocellular carcinoma is highest in HBeAg positive patients with high HBV DNA levels, but still the relative risk remains 10 for HBeAg negative patients. Furthermore it has been shown that when HBsAg is cleared before cirrhosis has developed, the prognosis is excellent. Recently the investigators have shown that HBeAg negative patients with high HBV-DNA load and low baseline HBsAg levels had a significantly higher HBsAg clearance (positive predictive value of 85%) after combination therapy with peginterferon alfa2a (Peg-IFN) and adefovir.
Based on these results, a trial was designed to investigate whether combination of a nucleos(t)ide analogue combined with PegIFN, could also provoke a high rate of HBsAg clearance in chronic hepatitis B patients with low (HBV DNA <20,000 IU/mL) viral load.
Study design:
This is a three arm open-label prospective randomized controlled trial. 150 patients will be enrolled into the study after assessment of eligibility. All patients must have documented HBsAg positivity for longer than 6 months, HBeAg negativity, anti-HBe positivity, HBV DNA < 20,000 IU/mL and ALT < 5 * upper limit of normal. Patients with a Child Pugh class B or C will be excluded. Group 1 will consist of patients treated with Peg-IFN and adefovir, group 2 will consist of patients treated with Peg-IFN and tenofovir and group 3 will consist of untreated controls. Patients in group 1 and 2 will receive medication for the period of one year. For enrolment into the study a liverbiopsy at time of enrolment is compulsory and is advisable at end of treatment (week 48).
Study population: The study population will consist of 150 patients chronically infected with hepatitis B virus with low viral load and HBeAg negativity.
Main study parameters/endpoints:
The aim of this study is to investigate what proportion of HBeAg negative, inactive carriers of the hepatitis B virus with low (< 20,000 IU/mL) load will lose HBsAg when treated with nucleot(s)ide analogue/Peg-IFN combination therapy.
In this study the investigators hypothesize that both treatment with peg-interferon and ADF or Peg-IFN and TDF in HBeAg negative chronic hepatitis B patients with low HBV DNA viral load will induce a high rate of HBsAg loss, comparable to that in patients with high viral load after treatment with ADF and Peg-IFN.
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Chronic Hepatitis B
Intervention
Peg-Interferon alfa 2a + Adefovir dipivoxil, Peg-Interferon alfa 2a + Tenofovir disoproxil fumarate
Location
Academic Medical Center
Amsterdam
Noord-Holland
Netherlands
1100 AZ
Status
Recruiting
Source
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00973219
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Interferon Alfa-2c
A recombinant alfa interferon consisting of 165 amino acids with arginine at positions 23 and 34. It is used extensively as an antiviral and antineoplastic agent.
Interferon Alfa-2a
A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent.
Interferon Alfa-2b
A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent.
Interferon Type I
Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).
Interferon Regulatory Factor-1
An interferon regulatory factor that binds upstream TRANSCRIPTIONAL REGULATORY ELEMENTS in the GENES for INTERFERON-ALPHA and INTERFERON-BETA. It functions as a transcriptional activator for the INTERFERON TYPE I genes.
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