Safety and Immunogenicity of a Naked DNA-based Vaccine Therapy in Patients With Chronic Hepatitis B (RBM99026)
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|ClinicalTrials.gov Identifier: NCT00988767|
Recruitment Status : Completed
First Posted : October 2, 2009
Last Update Posted : October 5, 2009
|Condition or disease||Intervention/treatment||Phase|
|Chronic Hepatitis B||Biological: DNA vaccine||Phase 1|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Specific Vaccine Therapy in Chronic Hepatitis B Using a Naked DNA: Phase I Study Using a GMO|
|Study Start Date :||February 2001|
|Actual Primary Completion Date :||November 2003|
|Actual Study Completion Date :||October 2004|
Experimental: intramuscular injections
Patients received 4 injections of DNA vaccine at M0, M2, M4 and M10
Biological: DNA vaccine
patients received 1ml of DNA vaccine (1mg/ml) at Months 0,2,4,10
Other Name: pCMV-S2.S DNA
- Safety and tolerability (local and general) of the DNA vaccine injections [ Time Frame: every Months from month 0 to month 12 and then M15, M18, M21 and M22 ]
- Immunological responses [ Time Frame: before DNA injection (M0), after DNA injection and during follow-up (M1, M3, M5, M10, M11, M15) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00988767
|Service d'Hepatologie, Hopital Necker Enfants Malades|
|Paris, France, 75015|
|Principal Investigator:||Helene FONTAINE, MD||Assistance Publique des Hopitaux de paris, AP-HP|