Ignite Creation Date:
2024-05-06 @ 12:59 AM
Last Modification Date:
2024-10-26 @ 10:57 AM
Study NCT ID:
NCT01701336
Status:
COMPLETED
Last Update Posted:
2013-08-29
First Post:
2012-08-28
Brief Title:
Study of a Novel Therapeutic Vaccine Against Hepatitis C Using Ad6NSmut and MVA-NSmut in Chronically Infected Patients
Sponsor:
ReiThera Srl
Organization:
ReiThera Srl
Study Overview
Official Title:
Phase Ib Study to Assess the Safety and Immunogenicity of a Novel HCV Vaccine Based on the Sequential Injection of Ad6NSmut and MVA-NSmut Given in Combination With PEG-Interferon Alfa Plus Ribavirin for Re-treatment of Chronic Hepatitis C
Status:
COMPLETED
Status Verified Date:
2013-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HCV004
Brief Summary:
The purpose of this study is to determine whether administration of recombinant IMPs Ad6NSmut and MVA-NSmut experimental vaccines for hepatitis C in HCV chronically infected patients in combination with the standard Interferonribavirin therapy is safe and induces an immunological response
Detailed Description:
An effective antiviral T cell response can mediate HCV viral control and induce the spontaneous resolution of HCV during primary infection This observation strongly supports the case for the development of T cell induction strategies as a potential therapy for HCV A hallmark of persistent HCV infection when viral loads are high is a weak and narrowly focused HCV specific T cell response whereas in resolved infection with undetectable viral loads robust T cell responses are detected A very potent immunization strategy might overcome this problem and induce a strong and diversified cell mediated immune response against HCV
The rationale of using HCV vaccine in combination with PEG-IFNRBV is supported both by in vitro models and by mathematical models of HCV dynamics under antiviral therapy Studies of viral dynamics suggested that HCV RNA kinetics result from the sum of two major actions or phases inhibition of viral production and reduction of infected cells number The mathematical model relying on both HCV-RNA and alanine aminotransferase ALT measures after PEG-IFNRBV therapy suggests that the elimination of infected cells by the immune system could play a major role in sustaining viral reduction This view is in accordance with the results of a recent study showing that IFN-γ one of the cytokines secreted by CTLs Cytotoxic T Lymphocyte and NK Natural Killer cells is able to inhibit HCV genomic and subgenomic replication in an in vitro model In the mathematical description the parameter that represents the putative non lytic control of HCV replication during antiviral therapy is φ resulting from the difference π-δ0 where π and δ0 are the time constant of the second phase decay of viraemia and of the infected cells respectively Interestingly the median value of parameter φ which is inversely related to the half-life of HCV-RNA molecules in the infected cells after phase 1 was significantly higher in sustained responders than in transient responders and non responders NR In addition whereas the baseline HCV-RNA production was comparable in all patients regardless of their outcome the median value of the residual HCV-RNA production during therapy was significantly higher in NR than in responders This data support the hypothesis that to reach a sustained response and an efficacious control of the infection the elimination of the infected cells is more relevant than a strong inhibition of viral production All the above considerations support the hypothesis that vaccination might be a new therapeutic opportunity to a cohort of consecutive HCV genotype 1a and 1b infected patients who failed to respond to PEG-IFNRBV therapy Therefore a potent induction of T cell responses in chronically infected patients might be used in combination with the current antiviral therapy in order to achieve sustained response in previously partial responders or relapsers
The rationale of using HCV vaccine in combination with PEG-IFNRBV is supported both by in vitro models and by mathematical models of HCV dynamics under antiviral therapy Studies of viral dynamics suggested that HCV RNA kinetics result from the sum of two major actions or phases inhibition of viral production and reduction of infected cells number The mathematical model relying on both HCV-RNA and alanine aminotransferase ALT measures after PEG-IFNRBV therapy suggests that the elimination of infected cells by the immune system could play a major role in sustaining viral reduction This view is in accordance with the results of a recent study showing that IFN-γ one of the cytokines secreted by CTLs Cytotoxic T Lymphocyte and NK Natural Killer cells is able to inhibit HCV genomic and subgenomic replication in an in vitro model In the mathematical description the parameter that represents the putative non lytic control of HCV replication during antiviral therapy is φ resulting from the difference π-δ0 where π and δ0 are the time constant of the second phase decay of viraemia and of the infected cells respectively Interestingly the median value of parameter φ which is inversely related to the half-life of HCV-RNA molecules in the infected cells after phase 1 was significantly higher in sustained responders than in transient responders and non responders NR In addition whereas the baseline HCV-RNA production was comparable in all patients regardless of their outcome the median value of the residual HCV-RNA production during therapy was significantly higher in NR than in responders This data support the hypothesis that to reach a sustained response and an efficacious control of the infection the elimination of the infected cells is more relevant than a strong inhibition of viral production All the above considerations support the hypothesis that vaccination might be a new therapeutic opportunity to a cohort of consecutive HCV genotype 1a and 1b infected patients who failed to respond to PEG-IFNRBV therapy Therefore a potent induction of T cell responses in chronically infected patients might be used in combination with the current antiviral therapy in order to achieve sustained response in previously partial responders or relapsers
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2010-022700-49 | EUDRACT_NUMBER | None | None |