E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C infection |
Infección Crónica de Hepatitis C |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis C Infection |
Infección Hepatitis C |
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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 | 18.1 |
E.1.2 | Level | PT |
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 |
? In Part 2, the primary objectives are to evaluate the safety and efficacy (percentage of treatment-naïve subjects achieving SVR24) of OBV, PTV, RTV and DSV with or without RBV in HCV GT1-infected subjects and OBV, PTV, RTV with RBV in GT4-infected pediatric subjects with or without compensated cirrhosis. ? In Part 3, the primary and secondary objectives are to assess the durability of response for subjects who achieved SVR, to assess the persistence of specific HCV amino acid variants associated with drug resistance in subjects who experienced virologic failure, and to assess the impact of OBV, PTV, RTV with or without DSV coadministered with or without RBV on growth and development. |
En la Parte 2, el objetivo primario es evaluar la seguridad y eficacia (porcentaje de pacientes sin experiencia de tratamiento con una RVS24) de OBV, PTV, RTV, y DSV en pacientes pediátrico infectados con GT4 con o sin cirrosis compensada En la parte 3 , el objetivo primario y secundario es determinar la durabilidad de la respuesta en pacientes que alcanzaron la RVS, determinar la persistencia de variantes de aminoácidos específicas del VHC asociadas a resistencia a fármacos en pacientes que presentaron fracaso virológico y determinar el impacto de OBV, PTV, RTV con o sin DSV coadministrado con o sin RBV en el crecimiento y el desarrollo. |
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E.2.2 | Secondary objectives of the trial |
? Part 2 (Safety and Efficacy): To evaluate the percentage of treatment-naïve subjects with SVR12 and the percentage of treatment-naïve subjects with ALT normalization by the end of treatment. ? Part 3 (Long-term Follow-up): To assess the long term impact of OBV, PTV, RTV with or without DSV coadministered with or without RBV on growth and development. |
Parte 2 ( Seguridad y Eficacia) : Evaluar el porcentaje de pacientes sin experiencia de tratamiento con RVS12 y porcentaje de pacientes sin experiencia de tratamiento con normalización de ALT al final del tratamiento. Parte 3 ( Seguimiento a largo plazo): determinar a largo plazo el impacto de OBV, PTV, RTV con o sin DSV coadministrado con o sin RBV en el crecimiento y el desarrollo. |
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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 |
The Pharmacogenetic Sub-Study procedure is described in the M14-748 Protocol. DNA samples from the Pharmacogenetic Sub-study may be sequenced and data analyzed for genetic factors contributing to the disease or to the subject's response to OBV, PTV, DSV in terms of pharmacokinetics, efficacy, tolerability, and safety. Such genetic factors may include genes for drug metabolizing enzymes, drug transport proteins, genes within the target pathway, genes believed to be related to the disease or to drug response. Some genes currently insufficiently characterized or unknown may be understood to be important at the time of analysis. The samples may be analyzed as part of a multi-study assessment of genetic factors involved in the response to OBV, PTV, DSV, drugs of this class, or the disease state. The samples may also be used for the development of diagnostic tests related to OBV, PTV, DSV, drugs of this class, or the disease state. |
El procedimiento del sub-estudio farmacogenético está descrito en el protocolo M14-748. Las muestras de ADN del subestudio de farmacogenética pueden ser secuenciadas y los datos analizados para factores genéticos contribuyendo a la enfermedad o a la respuesta de los pacientes a OBV,PTV,DSV en términos de farmacocinética, eficacia , tolerabilidad, y seguridad. Esos factores genéticos pueden incluir genes para enzimas que metabolizan fármacos, proteínas de transporte de fármacos , los genes para el camino del objetivo, los genes que se cree están relacionados con la enfermedad o la respuesta al fármaco. Algunos genes actualmente insuficientemente caracterizados o desconocido puede que se consideren importantes en el momento del análisis. Las muestras pueden ser analizadas como parte de una evaluación multi-estudio de los factores genéticos implicados en la respuesta al OBV, PTV, DSV, fármacos de esta clase, o el estado de la enfermedad. Las muestras también se pueden utilizar para el desarrollo de pruebas de diagnóstico relacionados con OBV, PTV, DSV, fármacos de esta clase, o el estado de enfermedad. |
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E.3 | Principal inclusion criteria |
1. Positive anti-HCV Ab and HCV RNA greater than or equal to 1000 IU/mL at the time of screening. 2. HCV genotype 1 or 4 for enrollment into Part 2. 3. Parent or legal guardian with the willingness and ability to provide written informed consent and participant willing and able to give assent, as appropriate for age and country. |
1. Ac anti-VHC positivos y ARN del VHC ? 1.000 UI/ml en el momento de la selección 2. VHC genotipo 1 o 4 para la inclusión en la Parte 2. 3. Padre(s)/tutor(es) legal(es) con el deseo y la capacidad de dar el consentimiento informado por escrito y paciente con el deseo y la capacidad de dar su asentimiento, según corresponda por edad y país |
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E.4 | Principal exclusion criteria |
1. Women who are pregnant or breastfeeding. 2. Use of known strong inducers and inhibitors (e.g., gemfibrozil) of cytochrome P450 2C8 (CYP2C8) in participants receiving dasabuvir, or strong or moderate inducers of CYP3A, within 2 weeks or 10 half lives, whichever is longer, of the respective medication/supplement prior to study drug administration. 3. Positive test result for Hepatitis B surface antigen (HbsAg) or anti-HIV antibody (HIV Ab) test. 4. Current enrollment in another interventional clinical study, previous enrollment in this study, prior or current use of any investigational or commercially available anti-HCV agents other than IFNs or RBV or receipt of any investigational product within 6 weeks prior to study drug administration. |
1. Mujeres embarazadas o en periodo de lactancia 2. Uso de inductores e inhibidores fuertes conocidos (p. ej., gemfibrozilo) del citocromo P450 2C8 (CYP2C8) en pacientes tratados con dasabuvir, o inductores fuertes o moderados de CYP3A, en 2 semanas o 10 semividas, lo que sea más prolongado, del medicamento/suplemento correspondiente antes de la administración del fármaco del estudio. 3. Resultado positivo en la prueba de antígeno de superficie de la hepatitis B (HbsAg) o anticuerpo anti-VIH (Ac VIH). 4. Inclusión actual en otro estudio clínico intervencional, inclusión previa en este estudio, uso previo o actual de fármacos en investigación o comercializados frente al VHC distintos a IFN o RBV o recepción de algún fármaco en investigación en los 6 meses previos a la administración del fármaco del estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
? Part 2: The primary endpoint is the percentage of treatment-naïve subjects with SVR24 ? Part 3: The primary endpoints of the Long-term Follow-up study are the percentage of subjects who relapse and the percentage of subjects who have new HCV infection at any time up to the last follow-up in this study out of subjects who achieved SVR in the previous study and enroll in this study. |
Parte 2: El objetivo principal es el porcentaje de pacientes sin experiencia de tratamiento con RVS24 Parte 3 : El objetivo primario del seguimiento a largo plazo en el estudio es el porcentaje de pacientes que recaen y el porcentaje de pacientes que tienen nueva infección VHC en cualquier momento hasta el último seguimiento en este estudio de los pacientes que alcanzan RVS en el estudio previo y se incluyen en este estudio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
An interim analysis on all the study data from Parts 1, 2 and 3 will occur after approximately 30 subjects enrolled in the ? 12 to 17 years age group in Part 2 complete PT Week 24 or prematurely discontinue from the study. An interim analysis on all the study data from Parts 1, 2 and 3 will occur after approximately 100 treatment-naïve subjects enrolled in Part 2 complete PT Week 24 or prematurely discontinue from the study. The same interim analysis will be repeated or updated once all subjects enrolled into Part 2 complete PT Week 24 or prematurely discontinue from the study. |
El análisis intermedio de todos los datos del estudio de la Parte 1, 2 y 3 ocurrirá después de que aproximadamente 30 pacientes del grupo ? 12 a 17 años en Parte 2 completen la semana PT o discontinúen prematuramente del estudio. Un análisis intermedio de todos los datos del estudio de la Parte 1, 2 y 3 ocurrirá después de que aproximadamente 100 pacientes sin experiencia de tratamiento incluidos en la Parte 2 completen semana 24 PT o discontinúen prematuramente del estudio. El mismos análisis intermedio se repetirá o actualizará cunado todos los pacientes incluidos en la Parte 2 completen Semana 24 PT o discontinúen prematuramente del estudio |
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E.5.2 | Secondary end point(s) |
? Part 2: The percentage of treatment-naïve subjects who achieve SVR12; and the percentage of treatment-naïve subjects with ALT .normalization during treatment, defined as ALT ? ULN at the final treatment visit for subjects with ALT > ULN at baseline ? Resistance: For subjects with virologic failure and HCV RNA > 1000 IU/mL, the variants at each amino acid position (by population, deep, and/or clonal nucleotide sequencing) at available post baseline time points compared to baseline and prototypic reference standard sequences will be summarized by DAA target genes and accompanying listings will be provided. Growth and Development: The following growth and development endpoints will be calculated through Post-Treatment Week 24 in Part 1 and Part 2, and in Part 3 for later visits. Growth rate at each post baseline visit (defined as change in height over change in age from the previous visit); Height z score; Waist circumference; Tanner staging |
Parte 2: El porcentaje de pacientes sin experiencia en el tratamiento que alcancen RVS12, y el porcentaje de pacientes sin experiencia en el tratamiento con normalización de la ALT durante el tratamiento, definida como ALT ? LSN en la visita final de tratamiento en pacientes con ALT > LSN en el periodo basal Resistencia: En pacientes con fracaso virológico y ARN del VHC > 1.000 UI/ml, las variantes en cada posición de aminoácidos (por secuenciación de nucleótidos poblacional, profunda o clonal) en intervalos de tiempo posbasales disponibles comparado con el periodo basal y secuencias estándares de referencia prototípicas se resumirán por genes objetivo de los AAD, con listas acompañantes. Crecimiento y desarrollo: Se calcularán los siguientes resultados de crecimiento y desarrollo hasta la semana 24 postratamiento en las Partes 1 y 2 y en la Parte 3 para visitas posteriores. Ritmo de crecimiento en cada visita posbasal (definido como el cambio en la estatura respecto al cambio de edad desde la visita previa).Puntuación z de estatura, Perímetro de la cintura, Estadios de Tanner. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
An interim analysis on all the study data from Parts 1, 2 and 3 will occur after approximately 30 subjects enrolled in the ? 12 to 17 years age group in Part 2 complete PT Week 24 or prematurely discontinue from the study. An interim analysis on all the study data from Parts 1, 2 and 3 will occur after approximately 100 treatment-naïve subjects enrolled in Part 2 complete PT Week 24 or prematurely discontinue from the study. The same interim analysis will be repeated or updated once all subjects enrolled into Part 2 complete PT Week 24 or prematurely discontinue from the study. |
El análisis intermedio de todos los datos del estudio de la Parte 1, 2 y 3 ocurrirá después de que aproximadamente 30 pacientes del grupo ? 12 a 17 años en Parte 2 completen la semana 24 PT o discontinúen prematuramente del estudio. Un análisis intermedio de todos los datos del estudio de la Parte 1, 2 y 3 ocurrirá después de que aproximadamente 100 pacientes sin experiencia de tratamiento incluidos en la Parte 2 completen semana 24 PT o discontinúen prematuramente del estudio. El mismos análisis intermedio se repetirá o actualizará cuando todos los pacientes incluidos en la Parte 2 completen Semana 24 PT o discontinúen prematuramente del estudio |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 |
Part 2: Safety & Efficacy; Part 3: Dose Response |
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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 | 26 |
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 |
Belgium |
Canada |
Germany |
Italy |
Puerto Rico |
Spain |
Switzerland |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |