Ignite Creation Date:
2025-12-24 @ 11:40 PM
Ignite Modification Date:
2025-12-25 @ 9:31 PM
Study NCT ID:
NCT01296451
Status:
COMPLETED
Last Update Posted:
2016-04-26
First Post:
2011-02-09
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Study of a New MVA Vaccine for Hepatitis C Virus
Sponsor:
ReiThera Srl
Organization:
Study Overview
Official Title:
A Phase I Study to Assess the Safety and Immunogenicity of AdCh3NSmut and MVA-NSmut in Healthy Volunteers and Patients With Hepatitis C Virus Infection
Status:
COMPLETED
Status Verified Date:
2016-04
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:
The study is aimed at assessing the safety of AdCh3NSmut and the new candidate vaccine MVA-NSmut when administered sequentially, or alone, to healthy volunteers and patients with hepatitis C virus infection The study also aims at assessing the cellular immune response generated by AdCh3NSmut and MVA-NSmut administered as mentioned above.
Detailed Description:
The scientific rationale supporting this study can be summarised as follows: 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. Furthermore, mouse and other human models of persistent viral infection show that antigen load crucially determines the quality and quantity of the anti-viral T cell responses so generated \[17-18\]. This supports the case for the assessment of efficacy of T cell induction, a) in the setting of low viral loads following viral suppression with combination therapy, and b) in the setting of high viral loads. Since pre-existing anti-vector immunity to adenoviral vectors may limit vaccine efficacy, we have conducted a phase-I clinical trial in healthy human subjects using human (Ad6) and simian (AdCh3) adenoviral vectors found at low sero-prevalence in human populations, in a heterologous prime/boost regimen (study HCV001). The same vectors are also under investigation in HCV infected patients (HCV002). These vectors encode the HCV non-structural proteins with a genetically inactivated polymerase gene (NSmut). We have shown that both vectors are safe and highly immunogenic. In preclinical primate studies using identical vectors, heterologous boosting increased peak responses and long-term immunity. However, in humans it appears that, although HCV specific T-cell responses increase following boosting, the magnitude of this response is reduced compared to that observed during vaccine priming. This is probably due to the induction of cross-reactive immunity between the two vectors. In contrast, it has recently been shown that Modified Vaccinia Ankara (MVA) encoding the malaria antigen ME-TRAP very successfully boosts T-cell responses primed with a simian Adenovirus vector, inducing the highest level of CD4+ and CD8+ T-cell responses ever observed using a vectored vaccine and affording protection from malaria infection (A. Hill unpublished data).
For these reasons we now wish to assess an MVA construct encoding HCV NS that will be combined with AdCh3NSmut (or AdCh3NSmut1) in a heterologous prime/boost vaccination regimen to assess the safety and immunogenicity of this strategy in healthy and HCV infected patients. This study will address the following questions: In healthy volunteers:
1. Can vaccination with MVA-NSmut vector alone safely induce HCV specific T cell responses?
2. Can vaccination using a heterologous prime/boost vaccination schedule with AdCh3NSmut and MVA-NSmut safely induce HCV specific T cell responses?
In HCV infected patients can a heterologous prime/boost vaccination schedule using AdCh3NSmut and MVA-NSmut:
3. Safely induce HCV specific T cell responses during pegylated-interferon and ribavirin (combination) therapy for HCV genotype-1 infection, after a significant decline in viral load, 14 weeks into therapy?
4. Safely induce HCV specific T cell responses during combination therapy for HCV genotype-1 infection, 2 weeks into therapy?
5. Safely induce HCV specific T cell responses in patients with chronic HCV (not receiving combination therapy) and a high viral load?
6. Suppress viral load in patients with chronic HCV, not on treatment with IFN and Ribavirin? Since the effect of combination therapy on HCV specific T cells is currently debated (see below) we will compare the T cell responses generated by the therapeutic prime/boost vaccination schedule in this study, to a group of matched historical control patients treated with combination therapy in whom immunological assessment has been made in an identical way to that proposed in this study.
For these reasons we now wish to assess an MVA construct encoding HCV NS that will be combined with AdCh3NSmut (or AdCh3NSmut1) in a heterologous prime/boost vaccination regimen to assess the safety and immunogenicity of this strategy in healthy and HCV infected patients. This study will address the following questions: In healthy volunteers:
1. Can vaccination with MVA-NSmut vector alone safely induce HCV specific T cell responses?
2. Can vaccination using a heterologous prime/boost vaccination schedule with AdCh3NSmut and MVA-NSmut safely induce HCV specific T cell responses?
In HCV infected patients can a heterologous prime/boost vaccination schedule using AdCh3NSmut and MVA-NSmut:
3. Safely induce HCV specific T cell responses during pegylated-interferon and ribavirin (combination) therapy for HCV genotype-1 infection, after a significant decline in viral load, 14 weeks into therapy?
4. Safely induce HCV specific T cell responses during combination therapy for HCV genotype-1 infection, 2 weeks into therapy?
5. Safely induce HCV specific T cell responses in patients with chronic HCV (not receiving combination therapy) and a high viral load?
6. Suppress viral load in patients with chronic HCV, not on treatment with IFN and Ribavirin? Since the effect of combination therapy on HCV specific T cells is currently debated (see below) we will compare the T cell responses generated by the therapeutic prime/boost vaccination schedule in this study, to a group of matched historical control patients treated with combination therapy in whom immunological assessment has been made in an identical way to that proposed in this study.
Study Oversight
Has Oversight DMC:
True
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2009-018260-10 | EUDRACT_NUMBER | None | View |