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

This study has been completed.
Information provided by (Responsible Party):
Carlo Ferrari, Azienda Ospedaliero-Universitaria di Parma Identifier:
First received: July 26, 2011
Last updated: November 5, 2013
Last verified: November 2013
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 Intervention
Chronic Hepatitis C
Drug: Boceprevir

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Effect of Boceprevir Therapy on HCV-specific T Cell Responses: Perspectives of Immune Monitoring and Immune Therapy

Resource links provided by NLM:

Further study details as provided by Azienda Ospedaliero-Universitaria di Parma:

Primary Outcome Measures:
  • Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy [ Time Frame: 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 [ Time Frame: 2 years ]
    To assess whether different levels of efficiency of pre-treatment antiviral T cell responses can predict response to treatment.

Biospecimen Retention:   Samples With DNA
Sera and peripheral blood lymphomononuclear cells

Enrollment: 30
Study Start Date: April 2012
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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 Name: Peginterferon alfa-2b and ribavirin

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.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Naïve genotype 1 chronic hepatitis C patients

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
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Please refer to this study by its identifier: NCT01403181

Unit of Infectious Diseases and Hepatology
Parma, Italy, 43126
Sponsors and Collaborators
Azienda Ospedaliero-Universitaria di Parma
Principal Investigator: Carlo Ferrari, MD Azienda Ospedaliero-Universitaria di Parma
  More Information

Responsible Party: Carlo Ferrari, MD, Azienda Ospedaliero-Universitaria di Parma Identifier: NCT01403181     History of Changes
Other Study ID Numbers: AZOSPA
Study First Received: July 26, 2011
Last Updated: November 5, 2013

Keywords provided by Azienda Ospedaliero-Universitaria di Parma:
T cells

Additional relevant MeSH terms:
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Liver Diseases
Digestive System Diseases
Peginterferon alfa-2b
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents processed this record on April 24, 2017