Clinical trial NCT00988767: Safety and Immunogenicity of a Naked DNA-based Vaccine Therapy in Patients With Chronic Hepatitis B
Official title: Specific Vaccine Therapy in Chronic Hepatitis B Using a Naked DNA: Phase I Study Using a GMO
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Hepatitis B
Keywords: Hepatitis B
DNA vaccine
immunotherapy
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2009-10-02
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability (local and general) of the DNA vaccine injections
timeFrame: every Months from month 0 to month 12 and then M15, M18, M21 and M22
Secondary outcomes:
measure: Immunological responses
timeFrame: before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15)
Other outcomes:
Locations:
city: Paris
country: France
facility: Service d'Hepatologie, Hopital Necker Enfants Malades
Study officials:
affiliation: Assistance Publique des Hopitaux de paris, AP-HP
name: Helene FONTAINE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Scott-Algara D, Mancini-Bourgine M, Fontaine H, Pol S, Michel ML. Changes to the natural killer cell repertoire after therapeutic hepatitis B DNA vaccination. PLoS One. 2010 Jan 18;5(1):e8761. doi: 10.1371/journal.pone.0008761.