E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C infection |
Infección Cronica por Hepatitis C |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Hepatitis C infection |
Infección Cronica por Hepatitis C |
|
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 |
|
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 primary objective of this study is to evaluate the safety and antiviral efficacy, defined as the percentage of subjects with sustained virologic response 12 weeks post-dosing (SVR12; HCV RNA < LLOQ 12 weeks after the last dose of study drug). |
El criterio de valoración principal de la eficacia es el porcentaje de sujetos con RVS12 (ARN del VHC < LIC 12 semanas después de la última dosis de la medicación del estudio), tanto global como en función del tratamiento en el estudio previo. |
|
E.2.2 | Secondary objectives of the trial |
? to evaluate the percentage of subjects with sustained virologic response 24 weeks post-dosing (SVR24; HCV RNA < LLOQ 24 weeks after the last dose of study drug) and ? to evaluate the percentage of subjects with extended rapid virologic response (eRVR) (HCV RNA < LLOQ at Weeks 4 through 12 of therapy with ABT 450/r plus ABT-267 plus pegIFN plus RBV). |
? evaluar el porcentaje de sujetos con respuesta virológica sostenida 24 semanas después del tratamiento (RVS24; ARN del VHC < LIC 24 semanas después de la última dosis del fármaco del estudio) y ? evaluar el porcentaje de sujetos con respuesta virológica rápida prolongada (RVRp) (ARN del VHC < LIC en las semanas 4 a 12 del período TI) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must have experienced virologic failure as defined in a previous pegIFN-free Abbott DAA combination trial. 2. Female subjects of childbearing potential must be willing to use two effective forms of birth control (not including oral contraceptives or contraceptives containing ethinyl estradiol) while receiving study drug and for 6 months (or per local ribavirin label) after stopping study drug, unless abstinent from sexual intercourse. 3. Females must have negative results for pregnancy test performed on a urine specimen obtained on Study Day 1 (prior to dosing). 4. Males must be surgically sterile or agree to practice two effective forms of birth control throughout the course of the study, starting with Study Day 1 and for 6 months (or per local ribavirin label) after the last dose of study drug, unless abstinent from sexual intercourse. 5. Subject must be considered an appropriate candidate for pegIFN, RBV, ABT-450/r and ABT-267 therapy in the opinion of the investigator. |
1. El sujeto deberá haber presentado fracaso virológico conforme a la definición utilizada en un estudio previo de Abbott sobre el tratamiento combinado con AAD sin pegIFN. 2. Las mujeres con capacidad de procrear deben estar dispuestas a utilizar dos métodos anticonceptivos eficaces (sin incluir anticonceptivos orales o anticonceptivos que contengan etinilestradiol) mientras reciban la medicación del estudio y durante 6 meses (o conforme a la ficha técnica local de la ribavirina) después de suspender la medicación del estudio, a menos que no mantengan relaciones sexuales 3. Las mujeres deberán tener un resultado negativo en una prueba de embarazo realizada en una muestra de orina obtenida el día 1 del estudio (antes de la administración de la medicación del estudio). 4. Los varones tienen que estar esterilizados quirúrgicamente o deben acceder a utilizar dos métodos anticonceptivos eficaces durante el estudio, a partir del día 1 del estudio, y durante 6 meses después de la última dosis de la medicación del estudio (o lo que indique la ficha técnica local de la ribavirina), a menos que no mantengan relaciones sexuales. 5. El sujeto es un candidato adecuado para recibir tratamiento con pegIFN, RBV, ABT-450/r y ABT-267 en opinión del investigador. |
|
E.4 | Principal exclusion criteria |
1. In subjects with a null or partial response to pegIFN/RBV treatment (at the time of enrollment into the previous Abbott DAA combination study), the presence of variants relative to the subject's baseline sequence or to prototypic standard sequence at any of the following amino acid positions: NS3 protease 155, 156, or 168; NS5A 28, 29, 30, 31, 32, 58, or 93. 2. Females who are pregnant or plan to become pregnant, or breast-feeding, or males whose partners are pregnant or planning to become pregnant. 3. Use of known inhibitors (e.g., ketoconazole) or inducers (e.g., phenobarbital, rifampin, carbamazepine, St. John's Wort) of CYP3A and OATP1B1 (e.g., cyclosporine) within 1 month prior to study drug administration. 4. Use of any medications contraindicated for use with pegIFN, RBV or ritonavir within 2 weeks prior to study drug administration or 10 half-lives, whichever is longer. Prior to entering the study, subjects must be able to safely discontinue the contraindicated medication or switch to an acceptable alternative under supervision of the investigator. 5. Discontinuation of antiviral therapy due to intolerance or an adverse event in a previous Abbott DAA combination study. |
1. En el caso de sujetos con respuesta nula o parcial al tratamiento con pegIFN/RBV (en el momento de la incorporación al estudio previo de Abbott sobre el tratamiento combinado con AADanterior de Abbott sobre tratamiento combinado con AAD), presencia de variantes correspondientes a la secuencia basal del sujeto o a una secuencia patrón prototípica en cualquiera de las siguientes posiciones de aminoácidos: proteasa NS3 155, 156 o 168; NS5A 28, 29, 30, 31, 32, 58 o 93. 2. Mujeres que estén embarazadas o tengan previsto quedarse embarazadas o que estén lactando, o varones cuyas parejas estén embarazadas o tengan previsto quedarse embarazadas. 3. Uso de inhibidores (p. ej., ketoconazol) o inductores (p. ej., fenobarbital, rifampicina, carbamazepina, hipérico) conocidos de la CYP3A y del OATP1B1 (p. ej., ciclosporina) en el mes anterior a la administración de la medicación del estudio. 4. Uso de medicamentos contraindicados para el uso con pegIFN, RBV o ritonavir en las 2 semanas previas a la administración de la medicación del estudio o en un período previo equivalente a 10 semividas, lo que suponga más tiempo. Antes de entrar en el estudio, los sujetos deben poder suspender de forma segura la medicación contraindicada o sustituirla por una alternativa aceptable bajo la supervisión del investigador. 5. Suspensión del tratamiento antiviral debido a intolerancia o a un acontecimiento adverso en un estudio previo de Abbott sobre el tratamiento combinado con AAD. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of subjects with sustained virologic response 12 weeks after the last actual dose of study drug (including DAA, pegIFN, and RBV) (SVR12actual; HCV RNA < LLOQ 12 weeks after the last actual dose of study drug). The percentage of subjects with SVR12actual and the corresponding 95% exact binomial confidence interval will be calculated overall and by treatment group in the prior study |
El criterio de valoración principal de la eficacia es el porcentaje de sujetos con respuesta virológica sostenida 12 semanas después de la última dosis real de la medicación del estudio (incluidos los AAD, pegIFN y RBV) (RVS12real). El porcentaje de sujetos con RVS12real y el intervalo de confianza binomial exacto del 95 % correspondiente se calcularán de forma global y por grupo de tratamiento en el estudio previo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after the last dose of study drug |
12 semanas tras la última dosis de medicación de estudio |
|
E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are the percentage of subjects with sustained virologic response 24 weeks after the last actual dose of study drug (including DAA, pegIFN, and RBV) (SVR24actual; HCV RNA < LLOQ 24 weeks after the last actual dose of study drug) and the percentage of subjects with eRVR (HCV RNA < LLOQ at TI Weeks 4 through 12). The percentage of subjects with SVR24actual and eRVR and the corresponding 95% exact binomial confidence intervals will be calculated overall and by treatment group in the prior study. |
Los criterios de valoración secundarios de la eficacia son el porcentaje de sujetos con respuesta virológica sostenida 24 semanas después de la última dosis real de la medicación del estudio (incluidos los AAD, pegIFN y RBV) (RVS24real) y el porcentaje de sujetos con una RVRp (ARN del VHC < LIC en las semanas 4 a 12 en el subestudio 1). El porcentaje de sujetos con RVS24real y RVRp y el intervalo de confianza binomial exacto del 95 % correspondiente se calcularán de forma global y por grupo de tratamiento en el estudio previo. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 weeks after the last dose of study drug |
24 semanas tras la última dosis de la medicación de estudio |
|
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 | 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 | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
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 |
Australia |
Brazil |
Canada |
Chile |
France |
Germany |
Mexico |
New Zealand |
Puerto Rico |
Spain |
United Kingdom |
United States |
|
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
|
last subject last visit |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |