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

September 23, 2025 updated by: Institut National de la Santé Et de la Recherche Médicale, France

Specific Vaccine Therapy in Chronic Hepatitis B Using a Naked DNA: Phase I Study Using a GMO

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • Service d'Hepatologie, Hopital Necker Enfants Malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 56 years (Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
every Months from month 0 to month 12 and then M15, M18, M21 and M22

Secondary Outcome Measures

Outcome Measure
Time Frame
Immunological responses
Time Frame: before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15)
before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2001

Primary Completion (Actual)

November 1, 2003

Study Completion (Actual)

October 1, 2004

Study Registration Dates

First Submitted

October 1, 2009

First Submitted That Met QC Criteria

October 1, 2009

First Posted (Estimated)

October 2, 2009

Study Record Updates

Last Update Posted (Estimated)

September 26, 2025

Last Update Submitted That Met QC Criteria

September 23, 2025

Last Verified

October 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INSERM RBM99.026

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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