E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HCV infection and liver trasplant |
infección po VHC en pacientes recientemente trasplantados hepaticos |
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E.1.1.1 | Medical condition in easily understood language |
HCV infection and liver trasplant |
infección po VHC en pacientes recientemente trasplantados hepaticos |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019752 |
E.1.2 | Term | Hepatitis C virus (HCV) |
E.1.2 | System Organ Class | 100000004848 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024716 |
E.1.2 | Term | Liver transplantation |
E.1.2 | System Organ Class | 100000004865 |
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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 investigate the efficacy and tolerability of Grazoprevir and Elbasvir in liver transplant recipients with hepatitis C recurrence. |
El objetivo principal del estudio evaluar la eficacia (respuesta viral sostenida a 12 semanas tras la finalización del tratamiento, RVS12) de la combinación de Grazoprevir + Elbasvir ± Ribavirina en receptores de trasplante hepático |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the beneficial effect of antiviral therapy in liver function. - To assess the impact of therapy in kidney function. |
Los objetivos secundarios estudiar la RVS 4 y 24, la tolerabilidad del tratamiento, y el impacto del tratamiento en la función hepática y función renal de los pacientes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age between 18 and 78 year-old. - Previous liver transplantation (more than 6 months). - Genotype 1 and 4 infection. - Hepatitis C recurrence defined by the presence of abnormal liver function tests, positive HCV-RNA, histological signs of hepatitis C recurrence. - Viral load ≥ 10000 UI/mL. - Immunosuppression with tacrolimus and/or mycophenolate (Prednisone use is allowed at low dose, ≤10mg/d). - Treatment naïve or treatment experienced (Peg-RBV or triple therapy) |
- Edad entre 18 y 78 años. - Trasplante hepático (> 6 meses) - Infección por genotipo 1 o 4 - Recidiva de la hepatitis C tras el trasplante definida como: pruebas hepaticas anormales, ARN-VHC positive, o signos histológicos de recidiva de la hepatitis C. - Carga viral del VHC >10000 UI/ml - Inmunosupresión con tacrolimus y/o micofenolato (se permite dosis baja de prednisona, ≤10mg/d). |
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E.4 | Principal exclusion criteria |
- Genotype 2, 3, 5 or 6 infection. - Decompensated cirrhosis defined by the presence of actual or previous history of clinical decompensation including ascites, hepatic encephalopathy, variceal bleeding or spontaneous bacterial peritonitis, or a Child-Pugh B or C. - Hepatocellular carcinoma after liver transplantation. - Total bilirubin > 3 mg/dL. - Immunosuppression with cyclosporine or an mTOR inhibitor (everolimus or sirolimus). - Severe extrahepatic diseases: cardiovascular, respiratory, cerebrovascular and poorly controlled diabetes. - Platelets < 75 x 109 cells/L. - Neutrophil count < 0.5 x 109 cells/L. - Hemoglobin < 9 g/dL. - Albumin < 3g/dL. - HIV infection. - Hepatitis B infection. - Active intake of toxic amounts of alcohol or recreational drugs. - Females who are pregnant, become to be pregnant or breastfeeding or males whose partners are pregnant, become to be pregnant or breastfeeding. - Intake of disallowed medications including(but not limited to): 1. Antibiotics: clarithromycin, erythromycin, telithromycin, nafcillin, rifampin 2. Antifungals: itraconazole, ketoconazole, voriconazole 3. Antihypertensives: nifedipine 4. Anticonvulsants: carbamazepine, phenytoin, phenobarbital 5. Bosentan 6. Modafinil 7. St.Jonh’s Wort 8. Immunosuppressants: cyclosporin, everolimus, sirolimus 9. Diabetes agents: glibenclamide, glyburide 10. Lipid lowering agents: gemfibrozil 11. Eltrombopag 12. Lapatinib 13. HIV medications: efavirenz, etravirine, all ritonavir boosted and unboosted HIV protease inhibitors 14. Statins: simvastatin, fluvastatin, rosuvastatin at doses greater than 10 mg/d, atorvastatin at doses greater than 10 mg/d. |
- Cirrosis descompensada - Carcinoma hepatocelular de aparición tras el trasplante hepático. - Bilirrubina total > 3 mg/dL. - Inmunosupresión con Ciclosporina o in inhibidor de mTOR (everolimus o sirolimus). - Enfermedad extra-hepática grave: cardiovascular, respiratoria, cerebrovascular o diabetes mellitus mal controlada.. - Plaquetas < 75 x 109/L. - Neutrófilos < 0.5 x 109 cells/L. - Hemoglobina < 9 g/dL. - Albúmina < 3 g/L. - Infección por VIH o hepatitis B. - Ingesta active de drogas o alcohol. - Mujeres en embarazo o lactancia, o hombres con pareja en embarazo o lactancia. - Ingesta de medicamentos prohibidos. incluidos: 1.Antibiotics: clarithromycin, erythromycin, telithromycin, nafcillin, rifampin 2. Antifungals: itraconazole, ketoconazole, voriconazole 3. Antihypertensives: nifedipine 4. Anticonvulsants: carbamazepine, phenytoin, phenobarbital 5. Bosentan 6. Modafinil 7. St.Jonh’s Wort 8. Immunosuppressants: cyclosporin, everolimus, sirolimus 9. Diabetes agents: glibenclamide, glyburide 10. Lipid lowering agents: gemfibrozil 11. Eltrombopag 12. Lapatinib 13. HIV medications: efavirenz, etravirine, all ritonavir boosted and unboosted HIV protease inhibitors 14. Statins: simvastatin, fluvastatin, rosuvastatin at doses greater than 10 mg/d, atorvastatin at doses greater than 10 mg/d. |
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E.5 End points |
E.5.1 | Primary end point(s) |
6.2. Primary end point: Sustained virological response 12 (SVR12) defined as HCV-RNA undetectable at post-treatment week 12. |
Primario: respuesta viral sostenida a 12 semanas tras la finalización del tratamiento, RVS12) de la combinación de Grazoprevir + Elbasvir ± Ribavirina en receptores de trasplante hepático |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Sustained virological response 12 (SVR12) defined as HCV-RNA undetectable at post-treatment week 12. |
Indetectabilidad del VHC-RNA en la semana º12 post tratamiento |
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E.5.2 | Secondary end point(s) |
- To evaluate the beneficial effect of antiviral therapy in liver function. - To assess the impact of therapy in kidney function. |
Los objetivos secundarios estudiar la RVS 4 y 24, la tolerabilidad del tratamiento, y el impacto del tratamiento en la función hepática y función renal de los pacientes. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Sustained virological response 4 (SVR4) and 24 (SVR24) defined as HCV-RNA undetectable at post-treatment weeks 4 and 24, respectively. - Effects of antiviral therapy on renal function.(cleareance de creatinine) - Effects of antiviral therapy in liver function.(transaminases) - Tolerability of this combination in liver transplant recipients. |
- porcentaje de indetectabilidad para RNA-VHC en la semama 4 y 24 post tratamiento -Efectos del tratamiento en la funcion renal (cleareance de creatinina) - efectos del tratamiento en la función hepática (transaminasas) - tolerancia de la combinación del tratamiento en pacientes ttrasplantados hepárticos |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
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) | 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 | 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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 2 |
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 | 2 |
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 |