Effect of Boceprevir Therapy on HCV-specific T Cell Responses: Perspectives of Immune Monitoring and Immune Therapy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Observational
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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)
干预措施: Boceprevir (Drug)
结局指标
主要结局
Levels of HCV-specific T cell functions before, during and after therapy to measure functional restoration induced by therapy
时间窗: 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
次要结局
- Correlation of quality and intensity of pre-treatment HCV-specific T cell responses with outcome of therapy(2 years)
研究者
Carlo Ferrari
MD
Azienda Ospedaliero-Universitaria di Parma