| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic active hepatitis C never treated previously with anti-viral terapie |
| Epatite cronica attiva da virus dell’epatite C (HCV) mai precedentemente sottoposti a terapie anti-virali per HCV |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic active hepatitis C never treated previously with anti-viral terapie |
| Epatite cronica attiva da virus dell’epatite C (HCV) mai precedentemente sottoposti a terapie anti-virali per HCV |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10019755 |
| E.1.2 | Term | Hepatitis chronic active |
| E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Primary objective of this study is to define the effect of anti-viral therapy with boceprevir on protective adaptive immune responses in patients with chronic hepatitis C by assessing: - whether viral suppression and decline of antigenemia induced by antiviral therapy are associated with a progressive restoration of HCV-specific antiviral T cell functions; - to what extent functional reconstitution results in maturation of fully differentiated effector and memory T cells, as observed after spontaneous control of HCV infection; - whether a hierarchical restoration of different T cell functions occurs over time upon viral control in individual patients. |
| Gli obiettivo primario dello studio sarà di caratterizzare l'effetto della terapia antivirale con boceprevir sulle risposte immunitarie adattative proteggenti in pazienti con epatite cronica C valutando: - se la soppressione virale ed il declino del antigenemia indotti dalla terapia antivirale sono associati ad un ripristino progressivo delle funzioni antivirali dei linfociti T HCV-specifici; - in che misura la ricostituzione immunologica conduca alla maturazione di linfociti T completamente differenziati in termini di memoria e di funzioni effettrici, come si osserva dopo controllo spontaneo dell'infezione da HCV; - se il ripristino funzionale T linfocitario si realizzi in modo progressivo e gerarchico in funzione del tempo di soppressione virale. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess whether the efficiency of pre-treatment antiviral T cell responses can predict response to boceprevir treatment |
| Valutare se il livello di efficienza delle risposte T linfocitarie HCV-specifiche espresso prima dell’inizio del trattamento possa predire la risposta al trattamento stesso |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 · 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) ³ 12 g/dl WBC ³ 2.500 cells/mL with absolute neutrofil count ³ 1500 cells/mL If a woman of childbearing potential, must have negative serum b-human chorionic gonadotropin (b-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 |
| · Uomini e donne di età compresa tra 18 e 70 anni · Firma del consenso informato · Diagnosi di epatite cronica da HCV diagnosticata almeno 6 mesi prima del baseline (giorno 1), in soggetti con positività di HCV-RNA sierico e anticorpi anti-HCV, documentati da: § positività degli anticorpi anti-HCV, positività di HCV-RNA oppure positività del genotipo di HCV almeno sei mesi prima del baseline (giorno 1) oppure § biopsia epatica effettuata prima del baseline (giorno 1) con evidenza di epatite cronica · HCV-genotipo 1 · HCV-RNA rilevabile allo screening · BMI tra 18 e 36 Kg/m2 · Pazienti-naïve, definiti come pazienti che non sono mai stati sottoposti a trattamento antivirale specifico con pegInterferone e ribavirina, senza controindicazioni a pegInterferone e ribavirina · Rispetto dei seguenti paramentri di laboratorio allo screening: § ALT e AST £ 5 del limite superiore della norma (ULN) § emoglobina (Hb) ³ 12 g/dl § WBC ³ 2.500/mL con conta assoluta dei neutrofili ³ 1500/mL § In caso di donna fertile, b-HCG negativo allo screening e test di gravidanza delle urine negativo, eseguito nelle 24 ore precedenti la prima somministrazione dei farmaci in studio. § Uso di metodi anticoncezionali efficaci per donne in età fertile e nelle partner di pazienti maschi in età fertile (almeno due metodi contraccettivi efficaci, uno dei quali rappresentato da condom con spermicida) per tutta la durata della terapia e nei 7 mesi success |
|
| E.4 | Principal 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 · Ongoin alcohol abuse · History of clinical relevant drug abuse · Positive urine screen for cocaine, opiate etc, or methadone use |
| • Donne incinte o donne che possono desiderare diventare incinte durante il corso dello studio • Soggetti di sesso maschile con partner incinta o che sta progettando di diventare incinta entro sette mesi dall’ultima dose di ribavirina • Evidenza di infezione o di co-infezione con HCV di genotipo non 1 • Storia di emoglobinopatia • Storia di sarcoidosi • Storia di neoplasia invasiva diagnosticata o trattata nei 5 anni precedenti. • Malattie psichiatriche non trattate o significative, quali depressione severa, schizofrenia, psicosi, storia di tentato suicidio • Co-infezione con HBV o HIV • Uso cronico di agenti immunosopressivi sistemici • Presenza di disordini autoimmuni;soggetti con ipotiroidismo trattato e TSH normale possono essere arruolati • Storia di malattia cardiaca significativa • Evidenza clinica di malattia polmonare cronica • Cirrosi conosciuta • Storia di trapianto di organo solido • Sospetto di carcinoma epatocellulare • Patologia epatica cronica di eziologia non HCV • Abuso di alcool in atto • Storia di abuso rilevante di droga • Positività delle urine per cocaina, o oppiacei; uso di metadone |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Generation of novel information about the mechanisms of action through which the new anti-virals can inhibit HCV replication |
| Acquisizione di nuove conoscenze sui meccanismi d’azione con cui i nuovi anti-virali riescono ad inibire la replicazione di HCV |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Generation of novel information about the mechanisms of protective T cell mempry maturation after long-term exposure to high antigen concentrations; |
| Acquisizione di nuove conoscenze sui meccanismi di maturazione di memoria T linfocitaria proteggente dopo lungo tempo di esposizione dei linfociti ad alte concentrazioni di antigeni virali |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Characterization of functional T cell restoration during anti-viral therapy |
| Caratterizzazione dei meccanismi di recupero funzionale T-linfocitario in corso di terapia antiviral |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Completion of the laboratory immunological study |
| Completamento dello studio immunologico-laboratoristico |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 24 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 24 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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