E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Genotype 1 Hepatitis C Virus Infection |
Infezione da virus dell'epatite C di Genotipo 1 |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | Hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as plasma HCV RNA < LLoQ at 24 weeks post-treatment) of response guided therapy (RGT) with GS-5885 + GS-9451 + PEG/RBV or GS-5885 + PEG/RBV. |
Valutare l’efficacia antivirale misurata dalla risposta virologica sostenuta (SVR, definita come livelli di HCV RNA nel plasma < limite inferiore di quantificazione (LLoQ) 24 settimane dopo il trattamento) della terapia guidata dalla risposta (RGT) con GS-5885 + GS-9451 + PEG/RBV(peginterferone alfa-2a/ribavirina), o GS-5885 + PEG/RBV. |
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E.2.2 | Secondary objectives of the trial |
. To evaluate the safety and tolerability of each regimen . To characterize viral dynamics and steady state pharmacokinetics of GS-5885 and GS-9451 when administered with PEG and RBV . To characterize the viral resistance to GS-5885 and GS-9451 when administered in combination with PEG and RBV. |
• Valutare la sicurezza e la tollerabilità di ciascun regime • Definire la dinamica virale e la farmacocinetica allo stato stazionario di GS-5885 e GS-9451 somministrati con PEG e RBV • Definire la resistenza virale a GS-5885 e GS-9451 somministrati in combinazione con PEG e RBV. |
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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 |
PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:
Date:
Title:Viral Dynamics Substudy. Pharmacokinetic Substudy.
Objectives:Viral Dynamics Substudy: Up to 20 subjects (10 per Arm) will participate in a Viral Dynamics Substudy with sampling on Day 1 (t = 4, 6, 8 hrs post-dose), Day 2 (t = 24 hrs post-dose), Day 3 (t = 48 hrs postdose), on Day 5 (or 6 or 7 based on scheduling preference) and Day 10. Samples obtained will be used for determination of HCV RNA levels and analysis of genotypic and phenotypic characterization of viral isolates. Pharmacokinetic Substudy: Up to 24 subjects (approx. 12 subjects per Arm) will participate in a PK Substudy and will have serial PK collection (samples obtained up to 24 hours after dosing) performed at Week 2 to determine the steady state pharmacokinetics of GS-5885, GS-9451 and RBV.
OTHER SUBSTUDIES:
Retreatment Substudy: Retreatment will be available to subjects in Arm 1 who are randomized to stop treatment at Week 12 and who relapse through 24 weeks post-treatment.
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FARMACOCINETICA/FARMACODINAMICA:
Vers:
Data:
Titolo:Sottostudio sulla dinamica virale. Sottostudio sulla farmacocinetica.
Obiettivi:Sottostudio sulla dinamica virale: Fino a 20 soggetti (10 per Braccio) parteciperanno a un Sottostudio sulla dinamica virale con raccolta di campioni il Giorno 1 (t = 4, 6, 8 ore dopo la dose), Giorno 2 (t = 24 ore dopo la dose), Giorno 3 (t = 48 ore dopo la dose), Giorno 5 (o 6 o 7 in base alla preferenza di programmazione) e Giorno 10. I campioni saranno utilizzati per la determinazione dei livelli di HCV RNA e per le analisi genotipiche e fenotipiche.
Sottostudio sulla farmacocinetica: Fino a 24 soggetti (12 per Braccio) parteciperanno al Sottostudio sulla PK e saranno sottoposti ad un prelievo seriale per la PK (campioni ottenuti fino a 24 ore dopo il dosaggio) che sarà effettuato alla Settimana 2 al fine di stabilire la farmacocinetica allo stato stazionario di GS-5885, GS- 9451 e RBV.
ALTRI SOTTOSTUDI:
Sottostudio di ripresa del trattamento: La ripresa del trattamento sarà disponibile per quei soggetti nel Braccio 1 che saranno nuovamente randomizzati per interrompere il trattamento alla Settimana 12 o che presenteranno recidiva nelle 24 settimane dopo il trattamento.
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E.3 | Principal inclusion criteria |
•Male or female, aged from 18 to 70 years old • Chronic HCV infection •Monoinfection with HCV GT 1 •HCV RNA > 104 IU/mL •HCV treatment naïve •Candidate for PEG/RBV therapy • Body mass index (BMI) between 18 and 36 kg/m2. |
• Uomini e donne di età compresa tra i 18 ed i 70 anni • Infezione cronica da HCV • Monoinfezione da HCV genotipo 1 • HCV RNA > 104 IU/ml allo Screening • Naïve al trattamento dell’HCV • Candidati alla terapia con PEG/RBV • Indice di massa corporea (BMI) 18-36 kg/m2, compresi. |
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E.4 | Principal exclusion criteria |
• Pregnant female or male with pregnant female partner • Poorly-controlled diabetes mellitus • History of clinically significant hemoglobinopathy • History of clinically significant retinal disease • History of invasive malignancy diagnosed or treated within 5 years • Untreated or significant psychiatric illnesses • Contraindications for PEG or RBV therapy • Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) • Chronic use of systemically administered immunosuppressive agents • Presence of autoimmune disorders • Severe chronic obstructive pulmonary disease • History of significant cardiac disease • Known cirrhosis |
•Donne in stato di garavidanza o uomini con partner in gravidanza • Diabete mellito scarsamente controllato •Storia di emoglobinopatia clinicamente significativa • Storia di malattia retinica clinicamente significativa • Storia di patologia maligna invasiva diagnosticata o trattata entro 5 anni • Malattie psichiatriche importanti • Controindicazioni alla terapia con PEG o RBV • Co-infezione HBV o HIV • Impiego cronico di agenti immunosoppressivi somministrati per via sistemica •Patologie autoimmuni • Patologia polmonore cronica ostruttiva • Malattia cardiaca significativa • Cirrosi nota. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Plasma HCV RNA <LLoQ |
HCV RNA plasmatico < LLoQ |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 weeks post treatment |
24 settimane dopo il trattamento |
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E.5.2 | Secondary end point(s) |
vRVR, eRVR, pEVR, HCV RNA < LLoQ |
vRVR, eRVR, pEVR, HCV RNA < LLoQ |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 2, 4, 8, 12, 16, 20, 24, 36, 48 of treatment, and at Week 4, 12 and 24 post-treatment. |
Alle settimane 2, 4, 8, 12, 16, 20, 24, 36, 48 di trattamento, e alla settimana 4, 12 e 24 post-trattamento. |
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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 | 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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | No |
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 |
Australia |
New Zealand |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 0 |