E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C Infection |
Infección crónica por el virus de la hepatitis C (VHC) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Hepatitis C Infection |
Infección crónica por el virus de la hepatitis C (VHC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 objective of Cohort A is to evaluate the safety and pharmacokinetic (PK) profile of BI 207127 (potentially two doses) in combination with 120 mg once daily (q.d.) FDV and weight-based RBV in a small group of patients with moderate hepatic impairment (Child-Pugh B [CPB]) compared to patients with mild hepatic impairment (Child-Pugh A [CPA]) to define the BI 207127 dose to be used in Cohort B. The objective of Cohort B is to assess efficacy, safety, and pharmacokinetics of 24-week treatment of the BI 207127 dose selected in Cohort A in combination with 120 mg once daily (q.d.) FDV and weight ?based RBV in a larger group of chronically infected HCV GT1b patients with moderate hepatic impairment (CPB). |
El objetivo de la cohorte A es evaluar la seguridad y el perfil farmacocinético (FC) del BI 207127 (potencialmente dos dosis) en combinación con una dosis diaria (QD) de 120 mg de FDV y RBV en función del peso en un reducido grupo de pacientes con fallo hepático moderado (Child-Pugh B [CPB]) en comparación con pacientes con fallo hepático leve (Child-Pugh A [CPA]) para definir la dosis de BI 207127 que se usará en la Cohorte B. El objetivo de la cohorte B es evaluar la eficacia, la seguridad y la farmacocinética de un tratamiento durante 24 semanas con la dosis de BI 207127 seleccionada en la cohorte A en combinación con una dosis diaria (QD) de 120 mg de FDV y RBV en función del peso en un grupo mayor de pacientes con infección crónica por el GT1b del VHC y con fallo hepático moderado (CPB). |
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E.2.2 | Secondary objectives of the trial |
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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 |
Cohort B PK Substudy: For Cohort B, an intensive PK sub-study will be conducted to assess pre-dose and 4 post-dose samples at Day 1, 8 and Week 4 and 16. A total of 48 patients will participate. |
Subestudio de farmacocinética en Cohorte B: Se realizará un subestudio farmacocinético en la cohorte B para evaluar muestras tomadas anteriormente a la dosis y 4 tomadas despues de la dosis en los día 1, 8 y en la semana 4 y 16. Participarán un total de 48 pacientes |
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E.3 | Principal inclusion criteria |
Treatment naïve and experienced patients (prior relapse, interferon intolerant, and [allowed in Cohort A only] prior partial response). Chronic HCV infection of genotype 1 (GT1), sub-GT1b virus only. Liver cirrhosis defined as Metavir Grade=4 or Ishak Grade ?5 on liver biopsy or liver stiffness of ?13 kPa on fibroscan. |
Pacientes sin o con tratamiento previo (recidiva anterior, intolerantes al interferón y [solamente permitido en la cohorte A] con respuesta parcial previa). Infección crónica por el genotipo 1 (GT1) del virus de la hepatitis C (VHC), solamente el subtipo GT1b. Cirrosis hepática, definida como grado 4 en la escala Metavir o grado ? 5 en la escala de Ishak según biopsia hepática o rigidez hepática ? 13 kPa en elastografía de transición (Fibroscan®). |
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E.4 | Principal exclusion criteria |
HCV infection of mixed genotype (1/2, 1/3, and 1/4) or mixed sub-GT1a/1b or undefined diagnosed by genotypic testing at screening.
Liver disease due to causes other than chronic HCV infection which may include but is not limited to hemochromatosis, Wilson's disease, or autoimmune liver diseases.
HIV infection |
Infección por virus de hepatitis C (VHC) de genotipo mixto (1/2, 1/3, 1 y 4 /) o sub-GT1a/1b mixta o indefinida, diagnosticada mediante pruebas genotípicas en el cribado.
Enfermedad hepática debida a causas distintas de la infección crónica por el VHC que puede incluir pero no se limita a la hemocromatosis, enfermedad de Wilson, enfermedades autoinmunes hepáticas. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is Sustained Virologic Response at Week 12 post-treatment (SVR12): Plasma HCV RNA level <25 IU/mL at 12 weeks after EOT (End of Treatment). |
El criterio de valoración principal es la respuesta virológica sostenida en la semana 12 después del tratamiento (SVR12, por sus siglas en inglés): Concentración plasmática de ARN del VHC <25 UI/ml a las 12 semanas de la finalización del tratamiento (FDT). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint is at 12 weeks after EOT. |
El criterio de valoración principal es a las 12 semanas después de la finalización del tratamiento. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: ? SVR4: Plasma HCV RNA level <25 IU/mL at 4 weeks after EOT ? SVR24: Plasma HCV RNA level <25 IU/mL at 24 weeks after EOT |
Los criterios secundarios de valoración de la eficacia son: ? SVR4: Concentración plasmática de ARN del VHC <25 UI/ml a las 4 semanas de la finalización del tratamiento. ? SVR24: Concentración plasmática de ARN del VHC <25 UI/ml a las 24 semanas de la finalización del tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 4 weeks after EOT and 24 weeks after EOT |
a las 4 semanas después de la finalización del tratamiento y a las 24 semanas después de la finalización del tratamiento |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Cohorte A es abierta y cohorte B is doble-ciego |
Cohort A is open and Cohort B is double blind |
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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 | 5 |
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 | 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 |
France |
Germany |
Ireland |
Italy |
Netherlands |
Spain |
Switzerland |
United Kingdom |
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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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LVLS |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |