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
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis B
Biological: DNA vaccine pCMVS2.S
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 70
Study Start Date: January 2008
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00536627

Locations
France
FONTAINE Hélène
Paris, France
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Investigators
Principal Investigator: Hélène FONTAINE, MD Pôle d'Hépatologie, Hôpital COCHIN, PARIS, FRANCE
Study Chair: Jean-Pierre ABOULKER, MD INSERM SC-10, VILLEJUIF, FRANCE
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier: NCT00536627     History of Changes
Other Study ID Numbers: 2007-001682-15, ANRS HB02 VAC-ADN
Study First Received: September 26, 2007
Last Updated: December 16, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
DNA vaccine

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

ClinicalTrials.gov processed this record on August 20, 2014