Ignite Creation Date:
2024-05-06 @ 9:55 AM
Last Modification Date:
2024-10-26 @ 12:22 PM
Study NCT ID:
NCT03119025
Status:
COMPLETED
Last Update Posted:
2019-05-10
First Post:
2017-03-27
Brief Title:
Autologous Dendritic Cell Vaccine for Treatment of Patients With Chronic HCV-Infection
Sponsor:
Russian Academy of Medical Sciences
Organization:
Russian Academy of Medical Sciences
Study Overview
Official Title:
SafetyEfficacy of Vaccination With Autologous Dendritic Cells Pulsed With Recombinant HCV-Antigens Core and NS3 for Treatment of Patients With Chronic HCV-Infection
Status:
COMPLETED
Status Verified Date:
2019-02
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:
None
Brief Summary:
Clearance of HCV infection requires early and multi-specific HLA class I restricted CD8 T cell and class II restricted CD4 T cell responses to both structural Core and non-structural HCV proteins NS3 NS4A NS5A NS5B Dendritic cells DCs are professional antigen-presenting cells that link innate and adaptive immune responses and play a major role in priming initiating and sustaining strong anti-HCV T cell immune responses
The general objective of this study is to evaluate safety feasibility and clinical efficacy of therapeutic vaccination in genotype 1 HCV patients using autologous DCs pulsed with recombinant HCV-antigens Core and NS3 Expected effects DC vaccination induces CoreNS3-specific immune response and reduces viral load in patients with chronic HCV-infection
The general objective of this study is to evaluate safety feasibility and clinical efficacy of therapeutic vaccination in genotype 1 HCV patients using autologous DCs pulsed with recombinant HCV-antigens Core and NS3 Expected effects DC vaccination induces CoreNS3-specific immune response and reduces viral load in patients with chronic HCV-infection
Detailed Description:
Hepatitis C virus HCV has chronically infected an estimated 170 million people worldwide People infected with HCV are at risk for developing chronic liver diseases such as liver cirrhosis and primary hepatocellular carcinoma It has been estimated that HCV accounts for 27 of cirrhosis and 25 of hepatocellular carcinoma worldwide Therapy for chronically HCV-infected patients has involved a pegylated interferon-alpha and ribavirin pegIFNRBV and is still the only FDA-approved therapeutic combination However this therapy is expensive non-specific toxic and only effective in about 50 of genotype-1 HCV patients
An early immune response represented by the activation of NK cells the development of vigorous anti-HCV CD4 and CD8 T-cell responses and the appearance of HCV-specific antibodies is mounted by the host during acute HCV infection and leads to clearance of the virus However in the vast majority 85 of infected individuals HCV causes a persistent infection The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system
Although HCV genome is very variable with hundreds of serotypes and six genotypes several structural Core and nonstructural proteins NS3 NS4A NS5A NS5B are highly conserved among genotypes and subtypes It is apparent that clearance of hepatitis C infection requires early and multi-specific HLA class I restricted CD8 T cell and class II restricted CD4 T cell responses to both structural and non-structural HCV proteins
DCs are professional antigen-presenting cells that link innate and adaptive immune responses DCs play a major role in priming initiating and sustaining strong T cell responses against pathogen-derived antigens Therefore DC-based therapy represents a promising immunotherapeutic approach in terms of their propensity to establish anti-HCV adaptive immune responses
This trial is a prospective non-blinded interventional study to determine safety feasibility and clinical efficacy of therapeutic vaccination in genotype 1 HCV patients using autologous DCs pulsed with recombinant HCV-antigens Core and NS3 Our previous work has shown that the short-term loading of DCs with recombinant HCV proteins Core 1-120 and NS3 1192-1457 have no any marked inhibitory effect on maturation and functions of DCs
In experimental group thirty patients with chronic hepatitis C genotype 1 will be vaccinated via intracutaneous injection of monocyte-derived DCs generated in the presence of IFN-αGM-CSF and pulsed with recombinant HCV Core 1-120 and NS3 1192-1457 proteins The vaccination protocol will includes initiating one injection per week no 4 and maintaining one injection per month no 6 courses with subsequent 6-month of follow up
The safety will be determined by the evaluation of the number of participants with the adverse events Liver safety will be assessed by blood analysis and Ultrasound Patients will be monitored in a 2 months after completing of initiating course 7 months after completing of maintaining course and 13 months in a 6 months post-vaccination follow-up
An early immune response represented by the activation of NK cells the development of vigorous anti-HCV CD4 and CD8 T-cell responses and the appearance of HCV-specific antibodies is mounted by the host during acute HCV infection and leads to clearance of the virus However in the vast majority 85 of infected individuals HCV causes a persistent infection The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system
Although HCV genome is very variable with hundreds of serotypes and six genotypes several structural Core and nonstructural proteins NS3 NS4A NS5A NS5B are highly conserved among genotypes and subtypes It is apparent that clearance of hepatitis C infection requires early and multi-specific HLA class I restricted CD8 T cell and class II restricted CD4 T cell responses to both structural and non-structural HCV proteins
DCs are professional antigen-presenting cells that link innate and adaptive immune responses DCs play a major role in priming initiating and sustaining strong T cell responses against pathogen-derived antigens Therefore DC-based therapy represents a promising immunotherapeutic approach in terms of their propensity to establish anti-HCV adaptive immune responses
This trial is a prospective non-blinded interventional study to determine safety feasibility and clinical efficacy of therapeutic vaccination in genotype 1 HCV patients using autologous DCs pulsed with recombinant HCV-antigens Core and NS3 Our previous work has shown that the short-term loading of DCs with recombinant HCV proteins Core 1-120 and NS3 1192-1457 have no any marked inhibitory effect on maturation and functions of DCs
In experimental group thirty patients with chronic hepatitis C genotype 1 will be vaccinated via intracutaneous injection of monocyte-derived DCs generated in the presence of IFN-αGM-CSF and pulsed with recombinant HCV Core 1-120 and NS3 1192-1457 proteins The vaccination protocol will includes initiating one injection per week no 4 and maintaining one injection per month no 6 courses with subsequent 6-month of follow up
The safety will be determined by the evaluation of the number of participants with the adverse events Liver safety will be assessed by blood analysis and Ultrasound Patients will be monitored in a 2 months after completing of initiating course 7 months after completing of maintaining course and 13 months in a 6 months post-vaccination follow-up
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None