E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus (HCV) genotype-1b Infection |
Virus de Hepatitis C (VHC) genotipo-1b |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis C Virus (HCV) genotype-1 Infection |
Virus de Hepatitis C (VHC) genotipo-1 Infección |
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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 | 16.0 |
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 |
The primary objectives are: - To evaluate the effect of steady-state simeprevir and daclatasvir on the steady-state pharmacokinetics of cyclosporine and tacrolimus when administered as a regimen containing simeprevir (150 mg qd), daclatasvir (60 mg qd) and RBV (1000 to 1200 mg per day) in post-OLT subjects with recurrent HCV genotype 1b infection - To evaluate the efficacy of a 24-week treatment regimen containing simeprevir, daclatasvir, and RBV with respect to the proportion of HCV genotype 1b infected post-OLT subjects achieving sustained virologic response 12 weeks after EOT (SVR12) |
Los objetivos principales son: - Para evaluar el efecto de simeprevir de estado estacionario y daclatasvir sobre la farmacocinética en estado estacionario de la ciclosporina y el tacrolimus cuando se administra como un régimen que contiene simeprevir (150 mg qd), daclatasvir (60 mg qd) y RBV (1000 a 1200 mg por día ) en sujetos post-OLT con infección por el VHC de genotipo 1b recurrente - Para evaluar la eficacia de un régimen de tratamiento de 24 semanas que contiene simeprevir, daclatasvir, y RBV con respecto a la proporción de VHC de genotipo 1b sujetos infectados después de la OLT lograron una respuesta virológica sostenida 12 semanas después del EOT (RVS12) |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To evaluate the pharmacokinetic profile of simeprevir and daclatasvir during a 24-week treatment regimen containing simeprevir, daclatasvir and RBV in post-OLT subjects with recurrent HCV genotype 1b infection - To determine the need for dose adjustment of cyclosporine and tacrolimus during a 24-week treatment regimen containing simeprevir, daclatasvir and RBV in post-OLT subjects with recurrent HCV genotype 1b infection - To evaluate the efficacy of a 24-week treatment regimen containing simeprevir, daclatasvir, and RBV with respect to the proportion of HCV genotype 1b infected post-OLT subjects achieving sustained virologic response 4 and 24 weeks after EOT (SVR4 and SVR24, respectively) - To evaluate safety and tolerability of a 24-week treatment regimen containing simeprevir, daclatasvir and RBV in post-OLT subjects with recurrent HCV genotype 1b infection |
Objetivos secundarios : Para evaluar el perfil farmacocinético de simeprevir y daclatasvir durante un régimen de tratamiento de 24 semanas que contiene simeprevir, daclatasvir y RBV en pacientes post-OLT con infección por el genotip 1b del VHC recurrente.Para determinar la necesidad de ajustar la dosis de ciclosporina y tacrolimus durante un régimen de tratamiento de 24 sem. que contiene simeprevir, daclatasvir y RBV en pacientes post-OLT con infección por el VHC de genotipo 1b recurrente Para evaluar la eficacia de un régimen de tratamiento de 24 semanas que contiene simeprevir, daclatasvir, y RBV con respecto a la proporción de VHC de genotipo 1b sujetos infectados después de la OLT lograron una respuesta virológica sostenida 4 y 24 semanas después del EOT(SVR4 y RVS24 respectivamente) Para evaluar la seguridad y la tolerabilidad de un régimen de tratamiento de 24 semanas que contiene simeprevir, daclatasvir y RBV en sujetos post-OLT con infección por VHC de genotipo 1b recurrente |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Liver transplant between 6 months and 10 years prior to the screening visit -Hepatitis C virus (HCV) genotype 1 subtype b infection - Screening HCV ribose nucleic acid level greater than 10,000 IU per milliliter - HCV treatment-naïve participants must not have received post-OLT treatment with any approved or investigational drug for the treatment of HCV - Receiving stable immunosuppressant therapy (ie, no change in dose in the last month) with cyclosporine or tacrolimus for more than 3 months prior to the screening visit |
- El trasplante de hígado entre los 6 meses y 10 años antes de la visita de selección -Virus de la hepatitis C (VHC) genotipo 1 subtipo B - Detección de ácido nucleico del VHC nivel ribosa mayor de 10.000 UI por mililitro - VHC participantes sin tratamiento previo no deben haber recibido un tratamiento post-OLT con cualquier fármaco aprobado o en fase de investigación para el tratamiento del VHC - Recepción de la terapia inmunosupresora estable (es decir, ningún cambio en la dosis en el último mes) con ciclosporina o tacrolimus durante más de 3 meses antes de la visita de selección |
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E.4 | Principal exclusion criteria |
- Evidence of acute or chronic hepatic decompensation after the liver transplantation (including ascites, bleeding varices or hepatic encephalopathy) - Any liver disease of non-HCV etiology, including current evidence of graft rejection except the presence of liver steatosis - Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of ribavarin - Coinfection with HCV of another genotype than genotype 1b, HIV type 1 or 2 (positive HIV-1 or HIV-2 antibodies test at screening), and hepatitis B virus (hepatitis B surface antigen positive) - Multi-organ transplant that included heart, lung, pancreas, or kidney |
- La evidencia de descompensación hepática aguda o crónica después del trasplante de hígado (como ascitis, várices sangrantes o encefalopatía hepática) - Cualquier enfermedad hepática de etiología no-HCV, incluyendo la evidencia actual de rechazo del injerto, excepto la presencia de esteatosis hepática - Cualquier otra enfermedad clínicamente significativa que, en opinión del investigador se ve agravada por los efectos conocidos de ribavirina - Coinfección con VHC de genotipo de otro genotipo 1b, el VIH tipo 1 o 2 (positivo VIH-1 o VIH-2 prueba de anticuerpos en la selección), y el virus de la hepatitis B (antígeno de superficie de hepatitis B positivo) - Trasplante de varios órganos que incluye corazón, pulmón, páncreas o riñón |
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E.5 End points |
E.5.1 | Primary end point(s) |
1 - Number of participants with a sustained virologic response (SVR)12 Weeks after the end of treatment 2 - Maximum Observed Plasma Concentration (Cmax) of cyclosporine and tacrolimus 3 - Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[last]) of cyclosporine and tacrolimus |
1 - Número de participantes con una respuesta virológica sostenida (RVS) 12 semanas después del final del tratamiento 2 - La concentración plasmática máxima (Cmax) de ciclosporina y tacrolimus 3 - Área bajo la curva concentración-tiempo de curva de cero cuando en cuando a última concentración cuantificable Observado (AUC [última]) de ciclosporina y tacrolimus |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 - Week 36 2 - Baseline, Week 2, 4, 8, 12 3 - Baseline, Week 2, 4, 8, 12 |
1 - Semana 36 2 - Línea de base, Semana 2, 4, 8, 12 3 - Línea de base, Semana 2, 4, 8, 12 |
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E.5.2 | Secondary end point(s) |
1 - Maximum Observed Plasma Concentration (Cmax) of simprenavir and daclatasvir 2 - Time to Reach Maximum Observed Plasma Concentration (Tmax) of simprenavir and daclatasvir 3 - Predose (trough) concentration (C0h) of simprenavir and daclatasvir 4 - Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of simprenavir and daclatasvir 5 - Number of participants with dose adjustment of cyclosporine and tacrolimus during treament with regimen simeprevir, daclatasvir and RBV 6 - Number of patients with a sustained virological response SVR4 after the end of treatment 7 - Number of participants with a sustained virologic response SVR24 after the end of treatment 8 - Number of participants with adverse events 9 - Number of participants with Undetectable HCV RNA (less than 25 IU/milliliter undetectable) and HCV RNA less than 25 IU/milliliter detectable 10 - Number of participants with HCV RNA level less than 100 IU/milliliter 11 - Number of participants with ontreatment failure after treatment with regimen simeprevir, daclatasvir and RBV 12 - Number of participants with viral relapse after treatment with regimen simeprevir, daclatasvir and RBV 13 - Number of participants with HCV NS3/4A and NS5A sequences |
1 - La concentración plasmática máxima (Cmax) de simprenavir y daclatasvir 2 - El tiempo para alcanzar la concentración plasmática máxima (Tmáx) de simprenavir y daclatasvir 3 - Predosis (valle) de concentración (C0h) de simprenavir y daclatasvir 4 - Área Bajo la Curva del Cero Tiempo al final del intervalo de dosificación (AUCtau) de simprenavir y daclatasvir 5 - Número de participantes con un ajuste de dosis de ciclosporina y tacrolimus durante Treament con régimen simeprevir, daclatasvir y RBV 6 - Número de pacientes con SVR4 respuesta virológica sostenida después del final del tratamiento 7 - Número de participantes con una respuesta virológica sostenida SVR24 después del final del tratamiento 8 - Número de participantes con eventos adversos 9 - Número de participantes con ARN del VHC indetectable (menos de 25 UI / mililitro indetectable) y de ARN del VHC de menos de 25 UI / mililitro detectable 10 - Número de participantes con nivel de ARN del VHC inferior a 100 UI / ml 11 - Número de participantes con insuficiencia ontreatment después del tratamiento con el régimen simeprevir, daclatasvir y RBV 12 - Número de participantes con recaída viral después del tratamiento con el régimen simeprevir, daclatasvir y RBV 13 - Número de participantes con VHC NS3/4A y secuencias NS5A |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - Baseline, Week 2, 4, 8, 12 2 - Baseline, Week 2, 4, 8, 12 3 - Baseline, Week 2, 4, 8, 12 4 - Baseline, Week 2, 4, 8, 12 5 - Part 1: Days 10 to 14 6 - Week 28 7 - Week 48 8 - Up to Week 48 9 - Weeks 2, 4, 12 and 24 10 - Week 4 11 - Screening, baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24 12 - Screening, baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24 13 - Screening, baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24 |
1 - Línea de base, Semana 2, 4, 8, 12 2 - Línea de base, Semana 2, 4, 8, 12 3 - Línea de base, Semana 2, 4, 8, 12 4 - Línea de base, Semana 2, 4, 8, 12 5 - Parte 1: días 10 al 14 de 6 - Semana 28 7 - Semana 48 |
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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 | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
- tolerability - HCV NS3/4A and NS5A sequences determination |
- tolerabilidad - NS3/4A de VHC NS5A y la determinación de secuencias |
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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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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
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Last visit of the last subject |
última visita del último sujeto |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |