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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00988767
Recruitment Status : Completed
First Posted : October 2, 2009
Last Update Posted : October 5, 2009
Information provided by:
Institut National de la Santé Et de la Recherche Médicale, France

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
Chronic Hepatitis B 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 B. 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
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 : February 2001
Actual Primary Completion Date : November 2003
Actual Study Completion Date : October 2004

Resource links provided by the National Library of Medicine

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 Name: pCMV-S2.S DNA

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

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00988767

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Service d'Hepatologie, Hopital Necker Enfants Malades
Paris, France, 75015
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
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Principal Investigator: Helene FONTAINE, MD Assistance Publique des Hopitaux de paris, AP-HP

Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Dr Helene FONTAINE, MD, principal investigator, AP-HP, Assistance publique des hopitaux de Paris Identifier: NCT00988767     History of Changes
Other Study ID Numbers: INSERM RBM99.026
First Posted: October 2, 2009    Key Record Dates
Last Update Posted: October 5, 2009
Last Verified: October 2009

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
Hepatitis B
DNA vaccine

Additional relevant MeSH terms:
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Hepatitis A
Hepatitis, Chronic
Hepatitis B
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
Immunologic Factors
Physiological Effects of Drugs