Boce-Par: Effect of Boceprevir on HCV-specific T Cell Responses

Sponsor

Azienda Ospedaliero-Universitaria di Parma (Other)

Overall Status

Completed

CT.gov ID

NCT01403181

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Boceprevir

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.

Study Design

Study Type:

Observational

Actual Enrollment :

30 participants

Time Perspective:

Prospective

Official Title:

Effect of Boceprevir Therapy on HCV-specific T Cell Responses: Perspectives of Immune Monitoring and Immune Therapy

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Chronic hepatitis C 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)	Drug: Boceprevir 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 Names: Peginterferon alfa-2b and ribavirin

Arm

Intervention/Treatment

Chronic hepatitis C

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)

Drug: Boceprevir

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 Names:

Peginterferon alfa-2b and ribavirin

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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