Effect of Boceprevir on HCV-specific T Cell Responses

NCT ID: NCT01403181

Last Updated: 2013-11-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-04-30

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.

Conditions

Chronic Hepatitis C

Keywords

HCV; T cells; cytokines; cytotoxicity; proliferation

Study Design

• Study Time Perspective: PROSPECTIVE

Study Groups

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)

Boceprevir

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Peginterferon alfa-2b and ribavirin

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Ospedaliero-Universitaria di Parma

OTHER

Sponsor Role: lead

Responsible Party

Carlo Ferrari

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carlo Ferrari, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero-Universitaria di Parma

Locations

Unit of Infectious Diseases and Hepatology

Parma, Italy, Italy

Countries

Italy

Other Identifiers

AZOSPA

Identifier Type: -

Identifier Source: org_study_id