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

This study has been completed.
Sponsor:
Information provided by:
Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier:
NCT00988767
First received: October 1, 2009
Last updated: October 2, 2009
Last verified: October 2009
  Purpose

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 Intervention Phase
Chronic Hepatitis B
Biological: DNA vaccine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Specific Vaccine Therapy in Chronic Hepatitis B Using a Naked DNA: Phase I Study Using a GMO

Resource links provided by NLM:


Further study details as provided by Institut National de la Santé Et de la Recherche Médicale, France:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunological responses [ Time Frame: before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15) ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: February 2001
Study Completion Date: October 2004
Primary Completion Date: November 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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: NCT00988767

Locations
France
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
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Helene FONTAINE, MD, principal investigator, AP-HP, Assistance publique des hopitaux de Paris
ClinicalTrials.gov Identifier: NCT00988767     History of Changes
Other Study ID Numbers: INSERM RBM99.026
Study First Received: October 1, 2009
Last Updated: October 2, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014