Efficacy and Tolerance of Naked DNA Vaccine in Patients With Chronic B Hepatitis (VAC-ADN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00536627
First received: September 26, 2007
Last updated: December 16, 2011
Last verified: December 2011

September 26, 2007
December 16, 2011
January 2008
November 2010   (final data collection date for primary outcome measure)
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 ]
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 ]
Complete list of historical versions of study NCT00536627 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Delay of appearance of virologic failure [ Time Frame: at Week 72 ]
  • Biological and clinical tolerance of DNA vaccine [ Time Frame: all along the trial ]
  • Immunological responses [ Time Frame: At weeks 18, 40, 46, 60, 72 ]
  • Clinical progression of hepatitis B [ Time Frame: all along the trial ]
Not Provided
Not Provided
 
Efficacy and Tolerance of Naked DNA Vaccine in Patients With Chronic B Hepatitis
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis B
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
  • Experimental: 1
    Patients will receive 5 injections of DNA vaccine at weeks 0, 8, 16, 40, 44.
    Intervention: Biological: DNA vaccine pCMVS2.S
  • No Intervention: 2

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
70
November 2010
November 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00536627
2007-001682-15, ANRS HB02 VAC-ADN
Yes
French National Agency for Research on AIDS and Viral Hepatitis
French National Agency for Research on AIDS and Viral Hepatitis
Not Provided
Principal Investigator: Hélène FONTAINE, MD Pôle d'Hépatologie, Hôpital COCHIN, PARIS, FRANCE
Study Chair: Jean-Pierre ABOULKER, MD INSERM SC-10, VILLEJUIF, FRANCE
French National Agency for Research on AIDS and Viral Hepatitis
December 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP