E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
HCV Genotype 1, 2, 4, 5 or 6 in treatment na¿ve subjects with compensated cirrhosis |
HCV di Genotipo 1,2,4,5 o 6 in soggetti con cirrosi compensata e na¿ve rispetto al trattamento |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019752 |
E.1.2 | Term | Hepatitis C virus (HCV) |
E.1.2 | System Organ Class | 100000004848 |
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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 |
To demonstrate the non-inferiority of the SVR12 rates of 8 weeks of treatment with the glecaprevir/pibrentasvir combination regimen to the historical SVR12 rate of 12 weeks of treatment with the glecaprevir/pibrentasvir in treatment na¿ve adults with chronic HCV GT 1, 2, 4, 5 or 6 infection and compensated cirrhosis. The primary efficacy objective will be assessed across genotypes, in the Per-Protocol (PP) population. To assess the safety of 8 weeks of treatment with the glecaprevir/pibrentasvir combination regimen in treatment na¿ve adults with chronic HCV GT 1, 2, 4, 5 or 6 infection and compensated cirrhosis. |
¿ Dimostrare la non inferiorit¿ dei tassi di risposta SVR12 per il trattamento della durata di 8 settimane con il regime combinato glecaprevir/pibrentasvir rispetto al tasso SVR12 storico ottenuto dal trattamento della durata di 12 settimane con glecaprevir/pibrentasvir in adulti affetti da infezione cronica da virus HCV di genotipo 1, 2, 4, 5 o 6 e cirrosi compensata che sono na¿ve al trattamento. L¿obiettivo primario di efficacia sar¿ valutato in maniera trasversale per tali genotipi nella popolazione PP (per protocol). ¿ Valutare la sicurezza del trattamento della durata di 8 settimane con il regime combinato glecaprevir/pibrentasvir in soggetti adulti affetti da infezione cronica da virus HCV di genotipo 1, 2, 4, 5 o 6 e cirrosi compensata, na¿ve al trattamento. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the non-inferiority of the SVR12 rates of 8 weeks of treatment with the glecaprevir/pibrentasvir combination regimen to the historical SVR12 rate of 12 weeks of treatment with the glecaprevir/pibrentasvir in treatment na¿ve adults with chronic HCV GT 1, 2, 4, 5 or 6 infection and compensated cirrhosis based on in the intention-to-treat (ITT) population. To assess the percentage of subjects with OTVF across genotypes in the intention-to-treat (ITT) population. To assess the percentage of subjects with post-treatment relapse across genotypes in the intention-to-treat (ITT) population. |
- Dimostrare la non inferiorit¿ dei tassi di risposta SVR12 per il trattamento della durata di 8 settimane con il regime combinato glecaprevir/pibrentasvir rispetto al tasso SVR12 storico ottenuto dal trattamento della durata di 12 settimane con glecaprevir/pibrentasvir in adulti affetti da infezione cronica da virus HCV di genotipo 1, 2, 4, 5 o 6 e cirrosi compensata nella popolazione Intention-to-Treat (ITT). - Valutare la percentuale di soggetti che manifestano fallimento virologico durante il trattamento (on-treatment virologic failure, OTVF) in maniera trasversale per i genotipi (nella popolazione ITT). - Valutare la percentuale di soggetti con recidiva post-trattamento rilevata in maniera trasversale per i genotipi (nella popolazione ITT). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, at least 18 years of age at time of Screening; 2. Screening laboratory result indicating HCV GT 1, 2, 4, 5 or 6 infection; 3. Positive plasma HCV antibody and HCV RNA viral load = 1000 IU/mL at Screening; 4. Treatment-naïve to any approved or investigational anti-HCV medication; 5. Subject must be documented as cirrhotic, with a Child-Pugh score of = 6. |
1. Soggetti di ambo i sessi, di età pari o superiore a 18 anni al momento dello Screening; 2. Infezione da HCV di genotipo 1, 2, 4, 5 o 6 confermata dai risultati degli esami di laboratorio eseguiti allo Screening; 3. Positività plasmatica per anticorpi anti-HCV e carica virale HCV RNA = 1000 UI/mL allo Screening; 4. Soggetti naïve rispetto al trattamento con qualsiasi medicinale anti-HCV approvato o sperimentale; 5. Soggetti per cui sia disponibile evidenza di cirrosi, con un punteggio Child-Pugh = 6. |
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E.4 | Principal exclusion criteria |
1. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study, or for approximately 30 days after the last dose of study drug; 2. Any current or historical clinical evidence of decompensated cirrhosis, including any current or past evidence of Child-Pugh B or C classification, hepatic encephalopathy or variceal bleeding, radiographic evidence ofsmall ascites, or empiric use of lactulose/rifaximin. The use of beta blockers is not exclusionary; 3. Current HBV or HIV infection on screening tests, defined as: • A positive HBsAg, or; • HBV DNA > LLOQ in subjects with isolated positive anti-HBc (i.e., negative HBsAg and Anti-HBs), or; • A positive anti-human immunodeficiency virus antibody (HIV Ab). 4. HCV genotype performed by the central laboratory during screening indicating genotype 3 infection or co-infection with more than one HCV genotype; 5. Screening laboratory analyses showing any of the following abnormal laboratory results: • Alanine aminotransferase ALT > 10 × ULN • Aspartate aminotransferase AST > 10 × ULN • Total Bilirubin > 3.0 mg/dL • Calculated creatinine clearance (CrCl, Cockcroft-Gault method) of < 50 mL/min • Albumin < 2.8 mg/dL • Hemoglobin < 10 g/dL • Platelets < 50,000 cells/mm3 6. History of suspected or confirmed hepatocellular carcinoma. |
1. Soggetto di sesso femminile in gravidanza, in allattamento o che intenda iniziare una gravidanza nel corso della sperimentazione o nei circa 30 giorni dopo l’ultima dose del medicinale sperimentale; 2.Qualsiasi evidenza clinica attuale o pregressa di cirrosi scompensata, compresa qualsiasi evidenza attuale o pregressa di Child-Pugh B o C, encefalopatia epatica oppure emorragia da varici, evidenza radiografica di ascite di grado lieve oppure uso empirico di lattulosio/rifaximina. L’uso di betabloccanti non rappresenta un criterio di esclusione; 3. Presenza attuale di infezione da HBV oppure HIV rilevata durante il periodo di Screening , definita come: • Positività per HBsAg, oppure; • HBV DNA > LLOQ in soggetti con positività isolata dell’anti-HBc (ovvero, negatività per HBsAg ed Anti- HBs), oppure; • Positività per HIV Ab (anticorpi anti-HIV). 4. Infezione da virus HCV di genotipo 3 confermata dal laboratorio centrale nel corso dello Screening oppure presenza di coinfezione con più di un genotipo del virus HCV; 5. Risultati delle analisi di laboratorio che indicano una delle seguenti alterazioni: • Alanina aminotransferasi ALT > 10 × ULN • Aspartato aminotransferasi AST > 10 × ULN • Bilirubina Totale > 3,0 mg/dl • Clearance della creatinina (CrCl calcolata mediante formula di Cockcroft-Gault) < 50 ml/min • Albumina < 2,8 mg/dl • Emoglobina < 10 g/dl • Piastrine < 50.000 cell/mm3 6. Storia di sospettato o confermato carcinoma epatocellulare |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the percentage of subjects who achieve SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug) across genotypes. |
L’obiettivo primario di efficacia consiste nella percentuale di soggetti che raggiungono la risposta SVR12 (HCV RNA < LLOQ 12 settimane dopo l'ultima dose attuale di farmaco sperimentale) in maniera trasversale nei genotipi. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks following the last dose of study drug |
12 settimane dopo l'ultima dose attuale di farmaco sperimentale |
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E.5.2 | Secondary end point(s) |
- SVR12 (HCV RNA<LLOQ 12 weeks after the last actual dose of study drug) for the subjects in the Intention-to-Treat population. - The percentage of subjects with HCV on-treatment virologic failure. - The percentage of subjects with post-treatment HCV relapse. |
- Tassi di SVR12 (HCV RNA< LLOQ 12 settimane dopo l'ultima dose attuale di farmaco sperimentale) per i soggetti nella popolazione Intention-to-Treat (ITT). - Percentuale di soggetti che manifestano fallimento virologico durante il trattamento. - Percentuale di soggetti con recidiva post-trattamento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 weeks following the last dose of study drug for Secondary Endpoint 1 and 2; 24 weeks following the last dose of study drug for Secondary Endpoint 3. |
12 settimane dopo l'ultima dose di farmaco sperimentale per l'end point secondario 1 e 2; 24 settimane dopo l'ultima dose di farmaco sperimentale per l'end point secondario 3 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Israel |
Mexico |
Puerto Rico |
Taiwan |
United States |
Vietnam |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |