Efficacy and Tolerance of Naked DNA Vaccine in Patients With Chronic B Hepatitis

Phase 1

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Biological: DNA vaccine pCMVS2.S

• Registration Number: NCT00536627
• Lead Sponsor: French National Agency for Research on AIDS and Viral Hepatitis

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2007-09-26
• Study First Submitted QC: 2007-09-27
• Study First Posted: 2007-09-28
• Study Start: 2008-01
• Primary Completion: 2010-11
• Study Completion: 2010-11
• Status Verified: 2011-12
• Last Update Submitted: 2011-12-16
• Last Update Posted: 2011-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• chronic hepatitis B with or without AgHBe
• no cirrhosis and no hepatocellular carcinoma
• treatment with NRTI unchanged for at least 3 months
• undetectable HBV viral load for 12 months
• HBV viral load < 12 IU/ml at screening
• sGPT < 5N
• tetanus immunization or booster dose for less than 8 years
• accurate birth control or menopausal women or sterility
• sickness insurance
• signed informed consent

Exclusion Criteria

• HLA-DR 15/16
• coinfections with HDV, HCV and/or HIV
• treatment with immunomodulators
• immunosuppressors
• long-term corticotherapy (over 4 weeks)
• active intravenous drug-users
• prolonged and excessive consumption of alcohol (men > 40g/day ; women > 30g/day ; for more than 5 years)
• medical history of autoimmune disease or presence of autoantibodies
• previous immunization by HBV vaccine of less than 5 years
• previous immunization by DNA vaccine against HBV
• personal or family medical history of demyelinising diseases
• uncontrolled hypophosphatemia
• renal failure, renal transplantation, haemodialysis
• pregnancy, breast-feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	DNA vaccine pCMVS2.S	Patients will receive 5 injections of DNA vaccine at weeks 0, 8, 16, 40, 44.

Primary Outcome Measures

Name	Time	Method
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	at week 72

Secondary Outcome Measures

Name	Time	Method
Clinical progression of hepatitis B	all along the trial
Delay of appearance of virologic failure	at Week 72
Biological and clinical tolerance of DNA vaccine	all along the trial
Immunological responses	At weeks 18, 40, 46, 60, 72

Trial Locations

Locations (1)

FONTAINE Hélène; 🇫🇷 Paris, France