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

NCT ID: NCT00988767

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-02-28
• Study Completion Date: 2004-10-31

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.

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intramuscular injections

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

Group Type: EXPERIMENTAL

DNA vaccine

Intervention Type: BIOLOGICAL

patients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10

Interventions

DNA vaccine

patients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10

Intervention Type: BIOLOGICAL

Other Intervention Names

pCMV-S2.S DNA

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helene FONTAINE, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique des Hopitaux de paris, AP-HP

Locations

Service d'Hepatologie, Hopital Necker Enfants Malades

Paris, , France

Countries

France

References

Mancini-Bourgine M, Fontaine H, Scott-Algara D, Pol S, Brechot C, Michel ML. Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers. Hepatology. 2004 Oct;40(4):874-82. doi: 10.1002/hep.20408.

Reference Type: BACKGROUND

PMID: 15382173 (View on PubMed)

Mancini-Bourgine M, Fontaine H, Brechot C, Pol S, Michel ML. Immunogenicity of a hepatitis B DNA vaccine administered to chronic HBV carriers. Vaccine. 2006 May 22;24(21):4482-9. doi: 10.1016/j.vaccine.2005.08.013. Epub 2005 Aug 18.

Reference Type: BACKGROUND

PMID: 16310901 (View on PubMed)

Scott-Algara D, Mancini-Bourgine M, Fontaine H, Pol S, Michel ML. Changes to the natural killer cell repertoire after therapeutic hepatitis B DNA vaccination. PLoS One. 2010 Jan 18;5(1):e8761. doi: 10.1371/journal.pone.0008761.

Reference Type: DERIVED

PMID: 20090916 (View on PubMed)

Other Identifiers

INSERM RBM99.026

Identifier Type: -

Identifier Source: org_study_id