E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C |
Hepatitis C crónica |
|
E.1.1.1 | Medical condition in easily understood language |
Viral infection called Hepatitis C which causes damage to the liver |
Infección viral denominada Hepatitis C que provoca daño en el hígado |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic 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 compare the sustained virological response of the following treatment regimens: - DNV/r with RO5024048 and Copegus® when administered for 24 weeks in patients with previous partial or null response to PEG-IFN/RBV treatment. - DNV/r with Pegasys® and Copegus® when administered for 24 weeks in patients with previous partial response to PEG-IFN/RBV treatment. - DNV/r and RO5024048 with Pegasy®s and Copegus® when administered for 24 weeks in patients with previous partial or null response to PEG-IFN/RBV treatment. - DNV/r and RO5024048 with Pegasys® and Copegus® when administered for 24 weeks followed by Pegasys® and Copegus® administered for an additional 24 weeks in patients with previous null response to PEG-IFN/RBV treatment. |
Comparar la respuesta virológica sostenida de las siguientes pautas de tratamiento en pacientes en los que ha fracasado al tratamiento previo con la asociación de interferón alfa pegilado más ribavirina: DNV/r con RO5024048 y Copegus® cuando se administra durante 24 semanas en pacientes con respuesta parcial o nula al tratamiento previo con IFN-PEG/RBV DNV/r con Pegasys® y Copegus® cuando se administra durante 24 semanas en pacientes con respuesta parcial al tratamiento previo con IFN-PEG/RBV DNV/r y RO5024048 con Pegasys ® y Copegus® cuando se administra durante 24 semanas en pacientes con respuesta parcial o nula al tratamiento previo con IFN-PEG/RBV DNV/r y RO5024048 con Pegasys® y Copegus® cuando se administra durante 24 semanas seguido de Pegasys® y Copegus® administrado durante otras 24 semanas en pacientes con respuesta nula al tratamiento previo con IFN-PEG/RBV |
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E.2.2 | Secondary objectives of the trial |
- To compare the safety (incidence of adverse events) of the following treatment regimens: danoprevir, RO5024048 and Copegus; danoprevir, Pegasys and Copegus; danoprevir, RO5024048, Pegasys and Copegus. - To determine virologic response over time - To characterize the pharmacokinetics of DNV and RO5024048 - To characterize the resistance profile of DNV and RO5024048 |
Comparar la seguridad y tolerabilidad de las tres pautas de tratamiento siguientes: DNV/r, RO5024048 y Copegus®, DNV/r, Pegasys® y Copegus® ,DNV/r, RO5024048, Pegasys y opegus® Determinar la respuesta virológica a lo largo del tiempo (todas las visitas). Caracterizar las características farmacocinéticas de DNV y RO5024048 Caracterizar el perfil de resistencia de DNV y RO5024048 |
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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 |
Roche Clinical Repository Specimens (RCR) |
Roche Clinical Repository Specimens (RCR); subestudio farmacocinético y muestras opcionales para el análisis IL28 y VHC. Para más detalles, ver protocolo WV21913. |
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E.3 | Principal inclusion criteria |
- Adult patients, age 18 years and older - Presence of hepatitis C infection, genotype 1a or 1b - Documentation of previous treatment failure after receiving approved doses of peginterferon plus ribavirin for at least 12 weeks - Patients must have discontinued prior hepatitis C treatment at least 12 weeks prior to study start |
Pacientes de ambos sexos de 18 años o mayores. Presencia de Infección por Hepatitis C, genotipo 1a o 1b Documentación de fracaso terapéutico previo después del inicio del tratamiento con las dosis aprobadas de IFN-PEG más RBV. durante al menos 12 semanas. Los pacientes deben haber suspendido el tratamiento previo para VHC al menos 12 semanas antes de ser incluidos (primera administración) en este estudio |
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E.4 | Principal exclusion criteria |
- Infection with any hepatitis C genotype or subtype other than genotype 1a or 1b - Patients with cirrhosis - Patients who were discontinued from previous peginterferon plus ribavirin therapy due to reasons other than insufficient therapeutic response - Co-infection with hepatitis B or human immunodeficiency virus (HIV) - History or evidence of chronic liver disease other than hepatitis C |
Infección con cualquier subtipo o genotipo de VHC diferente a genotipo 1a o 1b. Pacientes con cirrosis Pacientes que se retiraron del tratamiento IFN-PEG/RBV previo por motivos diferentes a respuesta terapéutica insuficiente Co-infección con hepatitis B o virus de la inmunodeficiencia humana (VIH) Antecedentes u otras pruebas de una enfermedad asociada con la hepatopatía crónica diferente a VHC |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary measure of efficacy is SVR-24 according to planned treatment duration. |
La variable principal de valoración de eficacia es RVS-24 de acuerdo con la duración prevista del tratamiento. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 weeks after the planned end of treatment |
24 semanas después del final del tratamiento previsto |
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E.5.2 | Secondary end point(s) |
- SVR-24 according to actual treatment duration, defined as the percentage of patients with undetectable HCV RNA 20 weeks after the actual end of treatment, as measured by Roche COBAS TaqMan HCV. - Virological response at clinical visits over time, defined as the percentage of patients with undetectable (< 25 IU/ml) HCV RNA as measured by the Roche COBAS TaqMan HCV test - Virological response at the end of treatment period, defined as the percentage of patients with undetectable (< 25 IU/ml) HCV RNA as measured by the Roche COBAS TaqMan HCV test at the last administration of study medication - Virological response at 12 weeks post treatment, defined as the percentage of patients with undetectable HCV RNA as measured by the Roche COBAS TaqMan HCV test at 12 weeks after the last dose of study medication (SVR-12 according to actual treatment duration) - Relapse rate, defined as the percentage of patients who achieved a virological response at the end of treatment but had detectable HCV RNA at the last assessment post treatment (among patients that had a virological response at the end of treatment and had at least one HCV RNA assessment post treatment) - Virological breakthrough, defined as the percentage of patients who achieved a virological response during treatment (viral load decline > 0.5 log10 followed by an increase of at least 0.5 log10 from on treatment nadir) before the end of danoprevir/r or RO5024058 treatment. |
- RVS-24 de acuerdo con la duración real del tratamiento, definido como el porcentaje de pacientes con ARN VHC indetectable ? 20 semanas después de la finalización real del tratamiento, determinado por Roche COBAS TaqMan VHC. - Respuesta virológica en las visitas clínicas a lo largo del tiempo, definida como el porcentaje de pacientes con ARN VHC indetectable (< 25 UI/ml) determinado por Roche COBAS TaqMan VHC test. - Respuesta virológica en el final del periodo de tratamiento, definido como el porcentaje de pacientes con ARN VHC indetectable (< 25 UI/ml) determinado por Roche COBAS TaqMan VHC test en la última administración del tratamiento del estudio. - Respuesta virológica en 12 semanas después del tratamiento, definido como el porcentaje de pacientes con ARN VHC indetectable determinado por Roche COBAS TaqMan VHC test en 12 semanas después de la última administración del tratamiento del estudio (RVS-12 de acuerdo con la duración real del tratamiento) - Tasa de recaída, definida como el porcentaje de pacientes que consiguieron respuesta virológica al final del tratamiento pero tenían ARN VHC detectable en la última valoración posterior al tratamiento (entre los pacientes que tenían una respuesta virológica al final del tratamiento y tenían al menos una valoración ARN VHC posterior al tratamiento) - Recaída virológica, definido como el porcentaje de pacientes que consiguieron respuesta virológica durante el tratamiento (disminución de la viremia > 0,5 log10 seguido de un aumento de al menos 0,5 log10 desde el mínimo del tratamiento) antes del final del tratamiento con danoprevir/r o RO5024058. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 weeks after the planned end of treatment. Up to four interim analyses of efficacy and safety data may be performed to inform the clinical development plan for RO5024048 and danoprevir. Interim analyses may be performed (1) when at least 80% of patients have completed approximately 12 weeks in the study, (2) when all patients have completed at least 24 weeks in the study, (3) when all patients have completed at least 36 weeks in the study, and (4) when all patients have completed at least 12 weeks of treatment-free follow up. |
24 semanas después del final del tratamiento previsto. Pueden realizarse un máximo de cuatro análisis de los datos de eficacia y seguridad para informar el plan de desarrollo clínico de RO5024048 y danoprevir. Los análisis intermedios pueden realizarse (1) cuando al menos el 80% de los pacientes han completado aproximadamente 12 semanas en el estudio, (2) cuando todos los pacientes han completado al menos 24 semanas en el estudio, (3) cuando todos los pacientes han completado al menos 36 semanas en el estudio, y (4) cuando todos los pacientes han completado al menos 12 semanas de seguimiento sin 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 | No |
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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 31 |
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 |
Austria |
Brazil |
Canada |
France |
Germany |
Italy |
Mexico |
Poland |
Spain |
United Kingdom |
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
|
See protocol |
Ver protocolo |
|
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 | 9 |
E.8.9.1 | In the Member State concerned days | 23 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 23 |