E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
HCV di Genotipo 1–6 in Soggetti con Compromissione Renale |
HCV Genotype 1-6 in subjects with Renal impairment |
|
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 |
|
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 assess the efficacy (by evaluating the percentage of subjects achieving SVR12) and safety of glecaprevir/pibrentasvir (GLE/PIB) in adults with chronic hepatitis C virus (HCV) genotype (GT) 1 – 6 infection with or without compensated cirrhosis and with chronic renal impairment in both HCV treatment-naïve and treatment experienced subjects. The efficacy of GLE/PIB will be assessed based on the overall population (i.e., across treatment durations, genotypes, and cirrhosis status) and the safety of GLE/PIB will be assessed by treatment duration and cirrhosis status across genotypes |
Valutare l’efficacia (valutando la percentuale di soggetti che ottengono la risposta SVR12) e la sicurezza di glecaprevir/pibrentasvir (GLE/PIB) in soggetti adulti con infezione cronica da virus dell’epatite C (HCV di genotipo 1 – 6, con o senza cirrosi compensata, e con compromissione renale cronica, compresi soggetti naïve rispetto al trattamento anti-HCV e soggetti che hanno ricevuto un pregresso trattamento anti-HCV. L’efficacia di GLE/PIB sarà valutata nella popolazione globale (ovvero in maniera trasversale per le diverse durate di trattamento, genotipi e lo stato relativo alla cirrosi) e la sicurezza di GLE/PIB sarà valutata sia in base alla durata del trattamento che allo stato relativo alla cirrosi in maniera trasversale per i diversi genotipi. |
|
E.2.2 | Secondary objectives of the trial |
To assess the percentage of subjects with HCV on-treatment virologic failure and the percentage of subjects with HCV virologic relapse across treatment durations, genotypes, and cirrhosis status. |
Valutare la percentuale di soggetti con HCV in fallimento da trattamento virologico e la percentuale di soggetti con recidiva virologica HCV in maniera trasversale per le diverse durate di trattamento, i diversi genotipi e lo stato relativo alla cirrosi. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Version: 20 gennaio 2017 Date: 20/01/2017 Title: Optional pharmacogenetic exploratory research. Objectives: Optional pharmacogenetic samples may be collected to conduct exploratory investigations into known and novel biomarkers.
|
Farmacogenetica Versione: 20 gennaio 2017 Data: 20/01/2017 Titolo: Ricerca esplorativa farmacogenetica opzionale. Obiettivi: I campioni di farmacogenetica opzionale possono essere raccolti per condurre indagini esplorative in biomarcatori noti e nuovi.
|
|
E.3 | Principal inclusion criteria |
1. Male or female at least 18 years of age at time of Screening. 2. Positive for anti-HCV antibody (Ab) at Screening and HCV RNA > 1,000 IU/mL at Screening. 3. Subject has an Estimated Glomerular Filtration Rate (eGFR) < 45mL/min/1.73 m2 as estimated by the MDRD method at screening according to the following formula: eGFR (mL/min/1.73 m2) = 175 × (Serum Creatinine) – 1.154 × Age – 0.203 × (0.742 if female) × (1.212 if black), or is dialysis-dependent. Subjects requiring dialysis should have been receiving dialysis for at least 1 month prior to enrollment, and may be on hemodialysis or peritoneal dialysis. 4. Screening laboratory result indicating HCV GT1-, 2-, 3-, 4-, 5- and/or6-infection. 5. Subject must be HCV treatment-naïve (i.e., patient has never received a single dose of any approved or investigational anti-HCV regimen) or treatment-experienced (i.e., subject has failed prior interferon [IFN] or pegylated interferon [pegIFN] with or without ribavirin [RBV], or sofosbuvir [SOF] plus RBV with or without pegIFN therapy). Prior HCV treatment with any other approved or investigational medications is not allowed. Previous HCV treatment must have been completed = 2 months prior to screening.
|
1. Soggetti di ambo i sessi, di età pari o superiore a 18 anni al momento dello Screening; 2. Positività per l’anticorpo (Ab) anti-HCV allo Screening e livelli di HCV RNA > 1.000 UI/mL allo Screening. 3. Soggetto con Tasso di Filtrazione Glomerulare Stimato (eGFR) < 45mL/min/1,73 m2 come stimato dal metodo MDRD allo screening secondo la seguente formula: eGFR (mL/min/1,73 m2) = 175 × (Creatinina Sierica)–1.154 × Età–0.203 × (0,742 se di sesso femminile) × (1,212 se di colore), oppure se dialisi-dipendente. I soggetti che necessitano di dialisi dovranno essere in dialisi da almeno 1 mese prima dell’arruolamento, e possono essere in emodialisi o dialisi peritoneale. 4. Risultati di laboratorio dello screening che indica infezione da HCV GT1-, 2-, 3-, 4-, 5- e/o 6. 5. Il soggetto deve essere naïve al trattamento HCV (cioè, il paziente non ha mai ricevuto una singola dose di qualsiasi regime anti-HCV approvato o sperimentale) oppure ha già ricevuto un trattamento (ovvero, soggetto che ha fallito una prima terapia con interferone [IFN] o interferone pegilato [pegIFN] con o senza ribavirina [RBV], o con sofosbuvir [SOF] più RBV con o senza pegIFN). Il trattamento pregresso con altri medicinali anti-HCV approvati o in fase di sperimentazione non è permesso. Il precedente trattamento HCV deve essere stato completato = (DA ALMENO) 2 mesi prima dello screening.
|
|
E.4 | Principal exclusion criteria |
Female who is pregnant, planning to become pregnant during the study, or breastfeeding during the study or for approximately 30 days after the last dose of study drug. 2. Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab). 3. Clinical history of acute renal failure in the 3 months prior to screening. 4. Clinically significant abnormalities or co-morbidities, or recent (within 6 months prior to study drug administration) alcohol or drug abuse that make the subject an unsuitable candidate for this study in the opinion of the investigator. 5. Receipt of any other investigational or commercially available direct acting anti HCV agents other than sofosbuvir (e.g., telaprevir, boceprevir, simeprevir, paritaprevir, grazoprevir, daclatasvir, ledipasvir, ombitasvir, elbasvir, velpatasvir or dasabuvir). |
1.Soggetto di sesso femminile che è in gravidanza, che sta allattando o che intende iniziare una gravidanza nel corso della sperimentazione o per 30 giorni circa dopo l’ultima dose del medicinale sperimentale. 2.Risultato positivo allo screening del test per l'antigene di superficie dell'epatite B (HBsAg) o per gli anticorpi anti-HIV (HIV Ab). 3.Storia clinica di insufficienza renale acuta nei 3 mesi precedenti lo screening. 4.Alterazioni o comorbilità clinicamente significative, oppure abuso recente (nei 6 mesi precedenti la somministrazione del medicinale sperimentale) di alcolici o sostanze stupefacenti che a giudizio dello sperimentatore rendono il soggetto un candidato non idoneo per la sperimentazione. 5.Soggetto che ha ricevuto qualsiasi agente anti-HCV ad azione diretta, sia sperimentale che commercializzato, diverso da sofosbuvir (es., telaprevir, boceprevir, simeprevir, paritaprevir, grazoprevir, daclatasvir, ledipasvir, ombitasvir, elbasvir, velpatasvir o dasabuvir).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug).
|
La variabile primaria di efficacia è SVR12 (HCV RNA < LLOQ 12 settimane dopo l’ultima dose effettivamente ricevuta del medicinale sperimentale). |
|
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 del medicinale sperimentale |
|
E.5.2 | Secondary end point(s) |
¿ The percentage of subjects with HCV on-treatment virologic failure. ¿ The percentage of subjects with post-treatment HCV relapse. |
• La percentuale di soggetti con HCV in fallimento da trattamento virologico • La percentuale di soggetti con recidiva virologica dopo il trattamento anti-HCV
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 weeks following the last dose of study drug |
24 settimane dopo l’ultima dose del medicinale sperimentale |
|
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 | 3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Korea, Republic of |
Puerto Rico |
United States |
Romania |
|
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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 20 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 20 |