Efficacy and Tolerance of Naked DNA Vaccine in Patients With Chronic B Hepatitis

NCT ID: NCT00536627

Last Updated: 2011-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2010-11-30

Brief Summary

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The purpose of this study is to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation.

Detailed Description

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Despite the availability of effective vaccines against hepatitis B, over 370 million people worldwide remain persistently infected with HBV. Persistent infection is associated with chronic liver disease that can lead to the developement of cirrhosis and hepatocellular carcinoma in two-third of persons. Treatment of chronic hepatitis B relies on the use of analogs such as lamivudine, adefovir, entecavir or immunostimulators such as interferons. Although analogs are efficient, genotypic resistance occurs after one year of treatment and the rate of virologic relapse is high after treatment discontinuation.

HBV is a non cytopathic virus and liver damage is caused by immune response against infected hepatocytes and to a non specific inflammatory response. Immune response contributes to the virus clearance. In acute hepatitis B infection, T cell response is polyclonal, specific and vigorous, whereas in patients with chronic infection, responses remain weak, less specific and hardly detectable in peripheral blood.

T cell responses could be induced or restored by antigenic stimulation such as vaccination. In a previous phase I clinical trial, we showed that DNA vaccination with plasmid pCMVS2.S is safe and can specifically, but transiently activate T-cell responses in chronic HBV-carriers not responding to current antiviral therapies.

Analogs such as lamivudine and adefovir were shown to enhance T cell responses concomitantly with viral load decrease. In this phase I/II clinical trial, we would like to determine if DNA vaccination of chronic HBV patients under treatment with NRTI can restore T-cell responsiveness and delay virologic reactivation after treatment discontinuation.

Conditions

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Chronic Hepatitis B

Keywords

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DNA vaccine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Patients will receive 5 injections of DNA vaccine at weeks 0, 8, 16, 40, 44.

Group Type EXPERIMENTAL

DNA vaccine pCMVS2.S

Intervention Type BIOLOGICAL

Patients will receive injections of 1 ml of vaccine (1 mg/ml) at weeks 0, 8, 16, 40 and 44

2

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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DNA vaccine pCMVS2.S

Patients will receive injections of 1 ml of vaccine (1 mg/ml) at weeks 0, 8, 16, 40 and 44

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* chronic hepatitis B with or without AgHBe
* no cirrhosis and no hepatocellular carcinoma
* treatment with NRTI unchanged for at least 3 months
* undetectable HBV viral load for 12 months
* HBV viral load \< 12 IU/ml at screening
* sGPT \< 5N
* tetanus immunization or booster dose for less than 8 years
* accurate birth control or menopausal women or sterility
* sickness insurance
* signed informed consent

Exclusion Criteria

* HLA-DR 15/16
* coinfections with HDV, HCV and/or HIV
* treatment with immunomodulators
* immunosuppressors
* long-term corticotherapy (over 4 weeks)
* active intravenous drug-users
* prolonged and excessive consumption of alcohol (men \> 40g/day ; women \> 30g/day ; for more than 5 years)
* medical history of autoimmune disease or presence of autoantibodies
* previous immunization by HBV vaccine of less than 5 years
* previous immunization by DNA vaccine against HBV
* personal or family medical history of demyelinising diseases
* uncontrolled hypophosphatemia
* renal failure, renal transplantation, haemodialysis
* pregnancy, breast-feeding
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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French National Agency for Research on AIDS and Viral Hepatitis

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hélène FONTAINE, MD

Role: PRINCIPAL_INVESTIGATOR

Pôle d'Hépatologie, Hôpital COCHIN, PARIS, FRANCE

Jean-Pierre ABOULKER, MD

Role: STUDY_CHAIR

INSERM SC-10, VILLEJUIF, FRANCE

Locations

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FONTAINE Hélène

Paris, , France

Site Status

Countries

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France

References

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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)

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)

Fontaine H, Kahi S, Chazallon C, Bourgine M, Varaut A, Buffet C, Godon O, Meritet JF, Saidi Y, Michel ML, Scott-Algara D, Aboulker JP, Pol S; ANRS HB02 study group. Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN. Gut. 2015 Jan;64(1):139-47. doi: 10.1136/gutjnl-2013-305707. Epub 2014 Feb 20.

Reference Type DERIVED
PMID: 24555998 (View on PubMed)

Godon O, Fontaine H, Kahi S, Meritet JF, Scott-Algara D, Pol S, Michel ML, Bourgine M; ANRS HB02 study group. Immunological and antiviral responses after therapeutic DNA immunization in chronic hepatitis B patients efficiently treated by analogues. Mol Ther. 2014 Mar;22(3):675-684. doi: 10.1038/mt.2013.274. Epub 2013 Dec 5.

Reference Type DERIVED
PMID: 24394187 (View on PubMed)

Other Identifiers

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ANRS HB02 VAC-ADN

Identifier Type: -

Identifier Source: secondary_id

2007-001682-15

Identifier Type: -

Identifier Source: org_study_id