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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Biological: DNA vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intramuscular injections<br>Patients received 4 injections of DNA vaccine at M0, M2, M4 and M10 | Biological: DNA vaccine<br>* patients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10<br>* Other names: pCMV-S2.S DNA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, DNA vaccine, immunotherapy