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RBM99026: Safety and Immunogenicity of a Naked DNA-based Vaccine Therapy in Patients With Chronic Hepatitis B

Sponsor
Institut National de la Santé Et de la Recherche Médicale, France (Other)
Overall Status
Completed
CT.gov ID
NCT00988767
Collaborator
(none)
10
Enrollment
1
Location
1
Arm
44
Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to investigate whether HBV-DNA vaccination is safe and could restore immune responses in patients with chronic hepatitis B non responder to available therapies.

Condition or Disease Intervention/Treatment Phase
  • Biological: DNA vaccine
 Phase 1

Detailed Description

  • Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Persistent infection is associated with chronic liver disease that can lead to the development of cirrhosis and hepatocellular carcinoma in some patients. Viral persistence is thought to be related to poor HBV-specific immune responses.

  • Interferon (IFN)-alpha treatment significantly decreases HBV replication in only one third of patients with hepatitis B e antigen (HBeAg)-positive chronic active hepatitis

  1. Nucleoside analogues, such as lamivudine and adefovir dipivoxil, inhibit HBV replication and improve histological signs of liver disease,but their use is limited by the risk of relapse after treatment discontinuation and the emergence of drug-resistant viral variants.

  • Patients with acute self-limited hepatitis B display detectable polyclonal and multispecific cytotoxic T lymphocyte and T helper (Th) responses to viral antigens,whereas these responses are weak or absent in chronic HBV carriers.

  • Increasing the strength of HBV-specific T-cell responses to the levels found in patients recovering from infection is therefore a goal in the treatment of patients with chronic hepatitis.

  • Immunization with a nucleic acid vaccine (DNA vaccine) usually elicits antibody responses and T lymphocytes with a Th1 cytokine profile. In animal models of chronic hepatitis B infection, including nonhuman primates, intramuscular injection of a plasmid encoding HBV envelope proteins induces rapid, strong, and sustained humoral and cell-mediated immune responses. Clinical trials of DNA vaccines for hepatitis B conducted in healthy adult volunteers using a plasmid encoding hepatitis B surface antigen and the gene gun as a delivery system showed good tolerance.

  • We carried out a phase I trial of a HBV DNA vaccine in patients with chronic active viral hepatitis, aiming to restore HBV-specific immune responses and to assess safety regarding liver disease.

Study Design

Study Type:
Interventional
Actual Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Specific Vaccine Therapy in Chronic Hepatitis B Using a Naked DNA: Phase I Study Using a GMO
Study Start Date :
Feb 1, 2001
Actual Primary Completion Date :
Nov 1, 2003
Actual Study Completion Date :
Oct 1, 2004

Arms and Interventions

Arm Intervention/Treatment
Experimental: intramuscular injections

Patients received 4 injections of DNA vaccine at M0, M2, M4 and M10

Biological: DNA vaccine
patients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10
Other Names:
  • pCMV-S2.S DNA

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety and tolerability (local and general) of the DNA vaccine injections [every Months from month 0 to month 12 and then M15, M18, M21 and M22]

    Secondary Outcome Measures

    1. Immunological responses [before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • chronic HBV carriers

    • biopsy proven chronic hepatitis

    • active HBV replication for > 6 months

    • non responding to Interferon-alpha or lamivudine treatment

    Exclusion Criteria:

    • co-infection with HIV, HCV, delta hepatitis virus

    • alcohol consumption> 40g/day

    • decompensated liver disease

    • HLA DR2

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Service d'Hepatologie, Hopital Necker Enfants Malades Paris France 75015

    Sponsors and Collaborators

    • Institut National de la Santé Et de la Recherche Médicale, France

    Investigators

    • Principal Investigator: Helene FONTAINE, MD, Assistance Publique des Hopitaux de paris, AP-HP

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00988767
    Other Study ID Numbers:
    • INSERM RBM99.026
    First Posted:
    Oct 2, 2009
    Last Update Posted:
    Oct 5, 2009
    Last Verified:
    Oct 1, 2009
    Keywords provided by , ,
    Hepatitis B
    DNA vaccine
    immunotherapy
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis B, Chronic
    Hepatitis
    Hepatitis, Chronic

    Study Results

    No Results Posted as of Oct 5, 2009