Effect of Boceprevir on HCV-specific T Cell Responses (Boce-Par)
|Study Design:||Time Perspective: Prospective|
|Official Title:||Effect of Boceprevir Therapy on HCV-specific T Cell Responses: Perspectives of Immune Monitoring and Immune Therapy|
- Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]Capacity of expansion, cytokine production (IFN-γ, IL-2 and TNF-α) and cytotoxicity expressed by HCV-specific T cells will be analyzed longitudinally at different time points before, during and after therapy
- Correlation of quality and intensity of pre-treatment HCV-specific T cell responses with outcome of therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]To assess whether different levels of efficiency of pre-treatment antiviral T cell responses can predict response to treatment.
Biospecimen Retention: Samples With DNA
|Study Start Date:||April 2012|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Chronic hepatitis C
In the experimental arm boceprevir (800 mg orally three times daily), PEG-IFN and ribavirin will be given for 24 weeks after the lead-in; the patients who will have undetectable HCV-RNA at week 8 will stop treatment at week 28; those who will be HCV-RNA positive at any visit between week 8 and 24 will receive an additional 20 weeks of PEG + RBV. Treatment will be discontinued if HCV-RNA is positive at week 24.
Immunological analysis will be performed longitudinally at the following time points: week -4, 0, 4 (end of lead-in), 8, 12, 24, 48, week 24 of follow-up. HCV-RNA will be quantified at the same time points and viremia will be correlated with immunological data.
Other Name: Peginterferon alfa-2b and ribavirin
Reconstitution of the antiviral T cell function may represent a component of the anti-viral effect of protease inhibitors. If T cell responsiveness is restored under therapy, potentiation of anti-viral T cell functions by exogenous T cell stimulation might be exploited to complement and to further improve response to available therapies. Monitoring the T cell function might also be useful to predict more accurately response to therapy.
To address these issues, phenotype and function of HCV-specific T cells will be analyzed longitudinally before, during and after therapy in naïve genotype 1 chronic hepatitis C patients treated with peginterferon plus ribavirin or with peginterferon and ribavirin plus boceprevir. To analyze the global CD4 and CD8 reactivity against all structural and non-structural HCV proteins a wide panel of peptides corresponding to the whole HCV genome of genotype 1 will be employed. To further analyze CD8 reactivity, HLA-A2/peptide tetramers will be used in HLA-A2 positive patients to directly quantify ex vivo HCV-specific CD8 cells circulating in the peripheral blood.The T cell function will be analyzed as capacity of expansion in vitro, cytokine production and cytotoxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01403181
|Unit of Infectious Diseases and Hepatology|
|Parma, Italy, 43126|
|Principal Investigator:||Carlo Ferrari, MD||Azienda Ospedaliero-Universitaria di Parma|