Effect of Boceprevir on HCV-specific T Cell Responses
- Registration Number
- NCT01403181
- Lead Sponsor
- Azienda Ospedaliero-Universitaria di Parma
- Brief Summary
Analysis of HCV-specific T cell responses in patients treated with boceprevir to assess whether therapy can induce restoration of the T cell function and to what extent this recovery can be achieved
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
- Male or female, aged from 18 to 70 years old, inclusive.
- Willing and able to provide written informed consent
- Chronic HCV infection for at least 6 month prior to baseline (Day 1) in subjects currently positive for HCV-RNA and anti-HCV antibody documented by:
- A positive anti-HCV antibody test, positive HCV-RNA assay, or HCV genotype test at least 6 month prior to baseline (Day 1) or
- A liver biopsy performed prior to baseline (Day 1) with evidence of chronic HCV infection
- Subjects must have liver biopsy results (performed no more than two years prior the screening) indicating the absence of cirrhosis
- HCV infection limited to genotype 1
- Detectable plasma HCV-RNA at screening
- BMI between 18 and 36 Kg/m2
- Eligible subjects must also be HCV treatment-naïve, defined as no prior exposure to PEG-INF and ribavirin, and must be eligible to standard of care therapy with PEG/RBV
- Subjects must have the following laboratory parameters at screening:
ALT and AST ≤ 5 x upper limit of normal range (ULN) Hemoglobin (Hb) ≥ 12 g/dl WBC ≥ 2.500 cells/μL with absolute neutrophil count ≥ 1500 cells/μL If a woman of childbearing potential, must have negative serum β-human chorionic gonadotropin (β-HCG) pregnancy test documented at the screening visit and a negative serum or urine pregnancy test before the first dose of study drug to ensure that they are not pregnant at the time of starting treatment A female subjects of childbearing potential and nonvasectomized male subjects with a female partners of childbearing potential must agree that they and their partner will use effective contraception (two separate forms of contraception simultaneously, one of which must be a male condom with spermicide) from screening throughout the duration of study treatment and for at least 7 months
- Pregnant women or women who may wish to become pregnant during the course of the study
- Male with a female who is pregnant or is planning to become pregnant within seven month the study of anticipated last dose of ribavirin
- Evidence of infection or co-infection with a no-genotype 1 HCV-strain
- History of hemoglobinopathy
- History of sarcoidosis
- History of invasive malignancy diagnosed or treated within 5 years.
- Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, history of a suicide attempt
- Co-infection with HBV or HIV
- Chronic use of systemic immunosuppressive agents
- Presence of autoimmune disorders; subjects with treated hypothyroidism with normal TSH may be enrolled
- History of significant cardiac disease
- Clinical evidence of chronic pulmonary disease
- Known cirrhosis
- History of solid organ transplantation
- Suspicion of hepatocellular carcinoma
- Chronic liver disease of a non-HCV etiology
- Ongoing alcohol abuse
- History of clinical relevant drug abuse
- Positive urine screen for cocaine, opiate etc, or methadone use
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Chronic hepatitis C Boceprevir * 10 naïve genotype 1 chronic hepatitis C patients treated with PEG plus RBV (control arm) * 20 naïve genotype 1 chronic hepatitis C patients treated with a response guided therapy consisting of Boceprevir in combination with PEG plus RBV (experimental arm)
- Primary Outcome Measures
Name Time Method Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy 2 years 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
- Secondary Outcome Measures
Name Time Method Correlation of quality and intensity of pre-treatment HCV-specific T cell responses with outcome of therapy 2 years To assess whether different levels of efficiency of pre-treatment antiviral T cell responses can predict response to treatment.
Trial Locations
- Locations (1)
Unit of Infectious Diseases and Hepatology
🇮🇹Parma, Italy