Clinical trial NCT01403181: Effect of Boceprevir on HCV-specific T Cell Responses
Official title: Effect of Boceprevir Therapy on HCV-specific T Cell Responses: Perspectives of Immune Monitoring and Immune Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Hepatitis C
Keywords: HCV
T cells
cytokines
cytotoxicity
proliferation
Lead sponsor: Azienda Ospedaliero-Universitaria di Parma
Sponsor class: OTHER
First posted: 2011-07-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Naïve genotype 1 chronic hepatitis C patients

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy
timeFrame: 2 years
Secondary outcomes:
measure: Correlation of quality and intensity of pre-treatment HCV-specific T cell responses with outcome of therapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Parma
country: Italy
facility: Unit of Infectious Diseases and Hepatology
Study officials:
affiliation: Azienda Ospedaliero-Universitaria di Parma
name: Carlo Ferrari, MD
role: PRINCIPAL_INVESTIGATOR
References: