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

Chronic Hepatitis B Clinical Trial

— RBM99026  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00988767
• Other study ID #: INSERM RBM99.026
• Status: Completed
• Phase: Phase 1
• First received: October 1, 2009
• Last updated: October 2, 2009
• Start date: February 2001
• Est. completion date: October 2004

Study information

• Verified date: October 2009
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 2004
• Est. primary completion date: November 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Endpoint Classification: Safety Study, Intervention Model: Single Group 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
patients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10

Locations

Country	Name	City	State
France	Service d'Hepatologie, Hopital Necker Enfants Malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

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	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	Yes
Secondary	Immunological responses		before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15)	No