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

Phase 1

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Biological: DNA vaccine

• Registration Number: NCT00988767
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2001-02
• Primary Completion: 2003-11
• Study Completion: 2004-10
• Status Verified: 2009-10
• Study First Submitted: 2009-10-01
• Study First Submitted QC: 2009-10-01
• Study First Posted: 2009-10-02
• Last Update Submitted: 2009-10-02
• Last Update Posted: 2009-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
intramuscular injections	DNA vaccine	Patients received 4 injections of DNA vaccine at M0, M2, M4 and M10

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Immunological responses	before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15)

Trial Locations

Locations (1)

Service d'Hepatologie, Hopital Necker Enfants Malades; 🇫🇷 Paris, France