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

Chronic Hepatitis B Clinical Trial

— VAC-ADN  

Official title:

Randomised, Opened, Multicentre Phase I/II Trial in Patients With Chronic Hepatitis B With HBV VL < 12 IU/ml and Under Treatment With NRTI, Which Evaluated Efficacy and Tolerance of Vaccination With Naked DNA on Viral Replication After Analogs' Treatment Interruption. ANRS HB02 VAC-ADN

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00536627
• Other study ID #: 2007-001682-15
• Secondary ID: ANRS HB02 VAC-AD
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 26, 2007
• Last updated: December 16, 2011
• Start date: January 2008
• Est. completion date: November 2010

Study information

• Verified date: December 2011
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Biological:
• DNA vaccine pCMVS2.S
Patients will receive injections of 1 ml of vaccine (1 mg/ml) at weeks 0, 8, 16, 40 and 44

Locations

Country	Name	City	State
France	FONTAINE Hélène	Paris

Sponsors (1)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis

Country where clinical trial is conducted

France, 

References & Publications (2)

Mancini-Bourgine M, Fontaine H, Bréchot 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. Epub 2005 Aug 18. — View Citation

Mancini-Bourgine M, Fontaine H, Scott-Algara D, Pol S, Bréchot 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary endpoint is virologic failure defined by 1) reactivation after analogs' treatment interruption, 2) virologic breakthrough during treatment with analogs, 3) the impossibility for the patients to interrupt treatment at week 48		at week 72	No
Secondary	Delay of appearance of virologic failure		at Week 72	No
Secondary	Biological and clinical tolerance of DNA vaccine		all along the trial	Yes
Secondary	Immunological responses		At weeks 18, 40, 46, 60, 72	No
Secondary	Clinical progression of hepatitis B		all along the trial	No