E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C Virus Infection (Genotypes 1 and 4) |
Hepatitis C crónica (genotipos 1 y 4) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Hepatitis C |
Hepatitis C crónica |
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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 | 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 assess efficacy, as determined by the proportion of subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12. |
Evaluar la eficacia, determinada por la proporción de pacientes con RVM12, definida con ARN del VHC < LDC en la semana 12 postratamiento. |
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E.2.2 | Secondary objectives of the trial |
? To assess safety, as measured by the frequency of SAEs and discontinuations due to AEs; ? To assess the relationship between efficacy endpoints and the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene. ? To assess the efficacy as determined by: ? HCV RNA undetectable at each of the following timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12 or post-treatment Week 24; ? HCV RNA < LOQ at each of the following timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; EOT (up to 24 weeks), post-treatment Week 24 (SVR24). ? To evaluate antiviral activity endpoints for HCV genotype 4 subjects;
+ see protocol section 1.3.3 for Exploratory objectives |
?Evaluar la seguridad, medida por la frecuencia de AAG y retiradas debido a AA; ?Evaluar la relación entre las variables de eficacia y los polimorfismos de nucleótido único (SNP) rs12979860 en el gen IL28B. ?Evaluar la eficacia determinada por: -ARN del VHC indetectable en cada uno de los siguientes puntos temporales: semanas 1, 2, 4, 6, 8 y 12; en ambas semanas 4 y 12 [RVRp]; FDT (hasta 24 semanas), semana 12 postratamiento o semana 24 postratamiento -ARN del VHC < LDC en cada uno de los siguientes puntos temporales: semanas 1, 2, 4, 6, 8 y 12; en ambas semanas 4 y 12 [RV(4y12)]; FDT (hasta 24 semanas), semana 24 postratamiento (RVM24). ?Evaluar las variables de actividad antiviral para los pacientes con VHC de genotipo 4;
- véase sección 1.3.3 del protocolo para objetivos exploratorios |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Males and females, ? 18 years of age; ? HCV Genotype 1 or 4 who previously failed treatment with P/R, classified as previous null and partial responders based on previous therapy; ? HCV RNA ? 10,000 IU/mL; ? Seronegative for HIV and HBsAg; ? Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population). |
?Hombres y mujeres >= 18 años de edad; ?VHC de genotipo 1 ó 4 que previamente no han respondido al tratamiento con P/R, clasificados como pacientes con respuesta nula y parcial basándose en el tratamiento previo; ?ARN del VHC >=104 UI/ml (10.000 UI/ml); ?Seronegativos para VIH y HBsAg; ?Se permiten los pacientes con cirrosis compensada (el reclutamiento de pacientes con cirrosis compensada se interrumpe cuando se alcanza aproximadamente el 25% de la población tratada). |
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E.4 | Principal exclusion criteria |
? Prior treatment of HCV with HCV direct acting antiviral (DAA); ? Evidence of a medical condition contributing to chronic liver disease other than HCV; ? Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy; ? Diagnosed or suspected hepatocellular carcinoma or other malignancies; ? Uncontrolled diabetes or hypertension; ? Total bilirubin ? 34 ?mol/L (or ? 2 mg/dL) unless subject has a documented history of Gilbert?s disease; ? Confirmed ALT ? 5x ULN; ? Confirmed Albumin < 3.5 g/dL (35 g/L) ? AFP > 100 ng/mL OR ? 50 and ? 100 ng/mL requires a liver ultrasound and subjects with findings suspicious of HCC are excluded; ? ANC < 1.5 x 10 billion cells/L (< 1.2 x 10 billion cells/L for Black/African-Americans); ? Confirmed Platelets < 90 x 10 billion cells/L; ? Hemoglobin < 12 g/dL for females or < 13 g/dL for males; ? Any criteria that would exclude the subject from receiving P/R. |
?Tratamiento previo del VHC con antivirales de acción directa (AAD) contra el VHC; ?Evidencia de un trastorno médico que contribuye a la hepatopatía crónica distinto a la infección por el VHC; ?Evidencia de enfermedad hepática descompensada incluidos, entre otros, antecedentes de o presencia de ascitis, varices hemorrágicas o encefalopatía hepática; ?Diagnóstico o sospecha de carcinoma hepatocelular u otros tumores; ?Diabetes o hipertensión no controladas; ?Bilirrubina total >= 34 micromol/l (o >= 2 mg/dl) salvo que el paciente tenga antecedentes documentados de enfermedad de Gilbert; ?ALT confirmada >= 5x LSN; ?Albúmina confirmada < 3,5 g/dl (35 g/l); ?Se excuyen los pacientes con AFP > 100 ng/ml O >= 50 y <=100 ng/ml, que requieren una ecografía hepática y se excluyen los pacientes con sospecha de CHC; ?RAN < 1,5 x 10^9 células/l (< 1,2 x 10^9 células/l en negros/afroamericanos); ?Plaquetas confirmadas < 90 x 10^9 células/l; ?Hemoglobina < 12 g/dl para mujeres o < 13 g/dl para hombres; ?Cualquier criterio que excluiría al paciente de recibir P/R; |
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E.5 End points |
E.5.1 | Primary end point(s) |
Antiviral activity, as determined by the proportion of genotype 1 subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for all subjects infected with HCV genotype 1. |
La actividad antiviral, determinada por la proporción de pacientes con genotipo 1 RVM12, definida con ARN del VHC < LDC en la semana 12 postratamiento para todos los pacientes infectados con VHC de genotipo 1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 12 weeks post-treatment |
Semana 12 postratamiento |
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E.5.2 | Secondary end point(s) |
? On-treatment safety, as measured by frequency of SAEs and discontinuations due to AEs through the end of treatment (maximum of 24 weeks) plus 7 days; ? Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene; ? Proportion of subjects with HCV RNA undetectable at each of the following timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12 or posttreatment Week 24; ? Proportion of subjects with HCV RNA < LOQ at each of the following timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; End of Treatment (EOT) (up to 24 weeks), posttreatment Week 24 (SVR24). ? Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects; |
? En el tratamiento de seguridad, medida por la frecuencia de AAG y retiradas debido a AA hasta final de tratamiento (máximo de 24 semanas) más 7 días; ? La proporción de pacientes con RVM12 (ARN del VHC <LDC en la semana 12 de post tratamiento) por los polimorfismos de nucleótido único (SNP) rs12979860 en el gen IL28B ? Proporción de pacientes con ARN del VHC indetectable en cada uno de los siguientes puntos temporales: semanas 1, 2, 4, 6, 8 y 12; en ambas semanas 4 y 12 [RVRp]; FDT (hasta 24 semanas), semana 12 postratamiento o semana 24 postratamiento. ? Proporción de pacientes con ARN del VHC <LDC en cada uno de los siguientes puntos temporales: semanas 1, 2, 4, 6, 8 y 12, en ambas semanas 4 y 12 [RV (4 y 12)]; final del tratamiento (FDT) (hasta a 24 semanas), la Semana 24 de post-tratamiento (RVM24). ? Proporción de pacientes con RVM12 (ARN del VHC <LDC en la semana 12 de post tratamiento) para los pacientes con VHC de genotipo 4 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
? Through the end of treatment (maximum of 24 weeks) plus 7 days; ? At post-treatment Week 12 ? Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12; EOT (up to 24 weeks), post-treatment Week 12 or post-treatment Week 24; ? Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12; End of Treatment (EOT) (up to 24 weeks), post-treatment Week 24. ? Post-treatment Week 12 |
?Hasta final del tratamiento (máximo de 24 semanas) más 7 días; ? Semana 12 posttratamiento ? Semanas 1, 2, 4, 6, 8 y 12; en ambas semanas 4 y 12 [RVRp]; FDT (hasta 24 semanas), semana 12 postratamiento o semana 24 postratamiento ? Semanas 1, 2, 4, 6, 8 y 12; en ambas semanas 4 y 12 [RVRp]; FDT (hasta 24 semanas), semana 24 postratamiento ? Semana 12 Post-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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
? Biomarker Assessments ? QoL ? Resistance testing |
?Evaluaciones de biomarcadores ? Calidad de vida ? Pruebas de resistencia |
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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) | 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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Argentina |
Canada |
Denmark |
France |
Germany |
Italy |
Korea, Republic of |
Mexico |
Netherlands |
Russian Federation |
Spain |
Sweden |
Switzerland |
Taiwan |
United States |
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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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The last visit will be considered the date of the last post-treatment visit. The end of the study will be considered the last subject?s last visit date or when the last data point required for statistical analysis is received from the last subject, whichever is later.
The primary analysis will occur when all subjects complete post-treatment Week 12, and a final analysis will occur once all subjects complete post-treatment Week 24. |
La última visita se considerará la fecha de la última visita de posttratamiento. El final del estudio se considerará la fecha de la última visita del último paciente, o cuando se reciba el último dato del último paciente necesario para el análisis estadístico, el que sea más tarde. El primer análisis se producirá cuando todos los sujetos hayan completado la semana 12 posttratamiento, y el análisis final,una vez que todos los pacientes hayan completado la semana 24 posttratamiento |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 2 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 2 |