E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C Virus Infection (Genotype 1b) |
Hepatitis C crónica con genotipo 1b |
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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 | 100000004862 |
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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 efficacy of Lambda/RBV/DCV to alfa-2a/RBV/TVR in subjects with chronic infection with HCV GT-1b, measured as the proportion of subjects who achieve SVR12 at post-treatment follow-up Week 12. |
Comparar la eficacia de lambda/RBV/DCV con alfa-2a/RBV/TVR en sujetos con infección crónica con el VHC de GT-1b, medida como el porcentaje de sujetos que alcanzan RVM12 en la semana 12 de seguimiento postratamiento |
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E.2.2 | Secondary objectives of the trial |
? To compare the proportion of subjects who achieve SVR12 in treatment-naive subjects at post-treatment follow-up Week 12 ? To compare the proportion of subjects with rash related dermatologic events of special interest reported during the first 12 weeks of treatment ? To compare the proportion of subjects who develop treatment emergent cytopenic abnormalities (anemia as defined by Hb <10 g/dL, and/or neutropenia as defined by ANC <750/mm³, and/or thrombocytopenia as defined by platelets <50,000/mm³) through EOT (max. 48 weeks) ? To compare the proportion of subjects with the following on-treatment interferon-associated symptoms through EOT (max. 48 weeks): ? Flu-like symptoms (as defined by pyrexia, chills or pain) ? Musculoskeletal symptoms (as defined by arthralgia, myalgia or back pain) ? To compare the proportion of subjects who achieve SVR24 (HCV RNA < LLOQ at post-treatment follow-up Week 24).
See Protocol sections 1.3.2 & 1.3.3 for additional objectives. |
?Comparar el porcentaje de sujetos que alcanzan RVM12 en sujetos que no han recibido tto previo en la semana 12 de seguimiento postto. ?Comparar el porcentaje de sujetos con acontecimientos dermatológicos de tipo exantema de especial interés notificados durante las 12 1ªs semanas de tto ?Comparar el porcentaje de sujetos que desarrollan anomalías citopénicas surgidas durante el tto(anemia definida como hemoglobina<10 g/dl y/o neutropenia, definida como RAN<750/mm3 y/o trombocitopenia, definida como plaquetas <50.000/mm3)hasta el Fin tto(FDT;máx 48 semanas) ?Comparar el porcentaje de sujetos con los siguientes síntomas asociados a interferón durante el tto hasta el FDT(máx48 semanas): -Síntomas pseudogripales(definidos por pirexia, escalofríos o dolor) -Síntomas musculoesqueléticos(definidos por artralgia, mialgia o lumbalgia) ?Comparar el porcentaje de sujetos que alcanzan RVM24(ARN del VHC<LIDC en la semana 24 postto). Ver sec 1.3.2&1.3.3 del protocolo para obj adicionales |
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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 |
Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific (version 1.0, dated 21-Jun-12) |
Enmienda nº1 de toma de muestra para farmacogenética (version 1.0 de fecha 21-jun-12) |
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E.3 | Principal inclusion criteria |
? Patients chronically infected with HCV GT-1b ? Naïve to prior treatment or documented evidence of relapse after 48 wks of treatment with alfa/RBV ? HCV RNA viral load ? 100,000 copies/mL at screening ? Patients with compensated cirrhosis are permitted |
?Pacientes con infección crónica por el VHC con GT-1b. ?Naïve al tratamiento previo o evidencia documentada de recaída después de 48 semanas de tratamiento con alfa / RBV. ?Carga viral del ARN del VHC >= 100.000 copias/ml en la selección ?Pacientes con cirrosis compensada están permitidos |
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E.4 | Principal exclusion criteria |
? Infection with HCV other than GT-1b ? Positive HBsAg or HIV-1/HIV-2 antibody test at screening ? Evidence of chronic liver disease caused by diseases other than chronic HCV infection ? Current evidence of or history of variceal bleeding, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of any of these findings on physical examination performed at screening ? Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to screening ? Evidence of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria ? Laboratory values: hemoglobin < 12.0 g/dL (males) or < 11.0 g/dL (females), platelets <90,000/mm³, total serum bilirubin ? 2 mg/dL (unless due to Gilbert?s disease) |
?Infección con VHC diferente al GT-1b. ?Prueba del HBsAg o anticuerpos anti-VIH1/VIH-2 positiva en la selección ?Signos de hepatopatía crónica causada por enfermedades diferentes a la infección crónica por el VHC ?Signos actuales o antecedentes de hemorragia varicosa, encefalopatía hepática o ascitis que requiere diuréticos o paracentesis o signos de cualquiera de estos hallazgos en la exploración física realizada durante la selección ?Cáncer o antecedentes de cáncer (salvo carcinoma in situ de cuello de útero o carcinoma de piel de células basales o escamosas) adecuadamente tratado en los 5 años anteriores al reclutamiento ?Evidencia de cirrosis descompensada basada en criterios radiológicos o resultados de la biopsia y criterios clínicos ?Valores de laboratorio: hemoglobina < 12,0 g/dl (hombres) o < 11,0 g/dl (mujeres), recuento de plaquetas < 90.000/mm3, bilirrubina sérica total >= 2 mg/dl (a menos que se deba a la enfermedad de Gilbert) |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the efficacy of Lambda/RBV/DCV to alfa-2a/RBV/TVR in subjects with chronic infection with HCV GT-1b, measured as the proportion of subjects with SVR12. |
Comparar la eficacia de lambda/RBV/DCV con alfa-2a/RBV/TVR en sujetos con infección crónica con el VHC de GT-1b, medida como el porcentaje de sujetos que alcanzan RVM12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis of primary endpoint will be conducted after all subjects reach the Week 12 post-treatment follow-up visit. An additional analysis will be conducted when all subjects complete the Week 24 post-treatment follow-up visit. |
Análisis de la variable principal de valoración se llevará a cabo después de que todos los pacientes hayan alcanzado la semana 12 de seguimiento postratamiento. Un análisis adicional se llevará a cabo cuando todos los sujetos hayan completado la semana 24 de seguimiento postratamiento |
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E.5.2 | Secondary end point(s) |
Proportion of subjects with ? SVR12 in naive ? dermatologic events ? treatment emergent cytopenic abnormalities ? on-treatment IFN associated flu-like/musculoskeletal symptoms ? SVR24 |
Porcentaje de sujetos con ?SVR12 en naive ?Eventos dermatológicos ?Anomalías citopénicas surgidas por el tratamiento ?Síntomas musculoesqueléticos asociados a interferón durante el tratamiento ?SVR24 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
? after all subjects reach the Week 12 post-treatment follow-up visit ? after all subjects complete the first 12 wks of treatment ? after all subjects complete treatment ? after all subjects complete treatment ? after all subjects reach the Week 24 post-treatment follow-up visit |
? después que todos los pacientes alcancen la semana 12 de seguimiento postratamiento ? después que todos los pacientes hayan completado las 12 primeras semanas de tratamiento ? después que todos los pacientes hayan completado tratamiento ? después que todos los pacientes alcancen la semana 24 de seguimiento postratamiento |
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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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
? Outcomes Research Hepatitis Physical Symptom Severity Diary: - ?Flu-like symptom? Index - HCV-Related Physical Symptoms - Hepatitis Quality of Life Questionnaire (HQLQ) - EQ-5D-3L - Healthcare Utilization and Productivity by Treatment Group
? Resistance Testing ? Immunogenicity Assessment |
Diario de intensidad de los síntomas físicos de la hepatitis : - índice de síntomas "similares a gripe" - VHC Relacionada con Síntomas Físicos - Cuestionario de Calidad de Vida (HQLQ) de Hepatitis - EQ-5D-3L -Utilización de recursos sanitarios y productividad por grupo de tratamiento. ? Pruebas de resistencia ? Evaluación de la inmunogenicidad |
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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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
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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LPLV
Analysis of primary endpoint will be conducted after all subjects reach the Week 12 posttreatment follow-up visit. An additional analysis will be conducted when all subjects complete the Week 24 post-treatment follow-up visit. |
Ultima visita del último paciente
Análisis de la variable principal de valoración se llevará a cabo después de que todos los pacientes hayan alcanzado la semana 12 de seguimiento postratamiento. Un análisis adicional se llevará a cabo cuando todos los sujetos hayan completado la semana 24 de seguimiento postratamiento |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 14 |