Efficacy and Tolerance of Naked DNA Vaccine in Patients With Chronic B Hepatitis (VAC-ADN)
The purpose of this study is to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomised, Opened, Multicentre Phase I/II Trial in Patients With Chronic Hepatitis B With HBV VL < 12 IU/ml and Under Treatment With NRTI, Which Evaluated Efficacy and Tolerance of Vaccination With Naked DNA on Viral Replication After Analogs' Treatment Interruption. ANRS HB02 VAC-ADN|
- Primary endpoint is virologic failure defined by 1) reactivation after analogs' treatment interruption, 2) virologic breakthrough during treatment with analogs, 3) the impossibility for the patients to interrupt treatment at week 48 [ Time Frame: at week 72 ] [ Designated as safety issue: No ]
- Delay of appearance of virologic failure [ Time Frame: at Week 72 ] [ Designated as safety issue: No ]
- Biological and clinical tolerance of DNA vaccine [ Time Frame: all along the trial ] [ Designated as safety issue: Yes ]
- Immunological responses [ Time Frame: At weeks 18, 40, 46, 60, 72 ] [ Designated as safety issue: No ]
- Clinical progression of hepatitis B [ Time Frame: all along the trial ] [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Study Completion Date:||November 2010|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
Patients will receive 5 injections of DNA vaccine at weeks 0, 8, 16, 40, 44.
Biological: DNA vaccine pCMVS2.S
Patients will receive injections of 1 ml of vaccine (1 mg/ml) at weeks 0, 8, 16, 40 and 44
|No Intervention: 2|
Despite the availability of effective vaccines against hepatitis B, over 370 million people worldwide remain persistently infected with HBV. Persistent infection is associated with chronic liver disease that can lead to the developement of cirrhosis and hepatocellular carcinoma in two-third of persons. Treatment of chronic hepatitis B relies on the use of analogs such as lamivudine, adefovir, entecavir or immunostimulators such as interferons. Although analogs are efficient, genotypic resistance occurs after one year of treatment and the rate of virologic relapse is high after treatment discontinuation.
HBV is a non cytopathic virus and liver damage is caused by immune response against infected hepatocytes and to a non specific inflammatory response. Immune response contributes to the virus clearance. In acute hepatitis B infection, T cell response is polyclonal, specific and vigorous, whereas in patients with chronic infection, responses remain weak, less specific and hardly detectable in peripheral blood.
T cell responses could be induced or restored by antigenic stimulation such as vaccination. In a previous phase I clinical trial, we showed that DNA vaccination with plasmid pCMVS2.S is safe and can specifically, but transiently activate T-cell responses in chronic HBV-carriers not responding to current antiviral therapies.
Analogs such as lamivudine and adefovir were shown to enhance T cell responses concomitantly with viral load decrease. In this phase I/II clinical trial, we would like to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation.
|Principal Investigator:||Hélène FONTAINE, MD||Pôle d'Hépatologie, Hôpital COCHIN, PARIS, FRANCE|
|Study Chair:||Jean-Pierre ABOULKER, MD||INSERM SC-10, VILLEJUIF, FRANCE|