Effect of Boceprevir on HCV-specific T Cell Responses

NCT01403181 | Completed DMC

• 1 other identifier: AZOSPA
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

Chronic Hepatitis C

Keywords

HCV; T cells; cytokines; cytotoxicity; proliferation

Outcome Measures

Primary Outcomes (1)

• Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy

  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

  2 years

Secondary Outcomes (1)

• Correlation of quality and intensity of pre-treatment HCV-specific T cell responses with outcome of therapy

  2 years

Study Arms (1)

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

Interventions

Boceprevir 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.

Also known as: Peginterferon alfa-2b and ribavirin

Chronic hepatitis C

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Naïve genotype 1 chronic hepatitis C patients

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Parma: lead

Study Sites (1)

Unit of Infectious Diseases and Hepatology

Parma, Italy, 43126, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Sera and peripheral blood lymphomononuclear cells

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; peginterferon alfa-2b; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Carlo Ferrari, MD

  Azienda Ospedaliero-Universitaria di Parma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 26, 2011
• First Posted: July 27, 2011
• Study Start: April 1, 2012
• Primary Completion: October 1, 2013
• Last Updated: November 6, 2013

Record last verified: 2013-11

Locations

IT (1)