Recurrent Hepatitis C MedDRA version: 16.1 Level: LLT Classification code 10070678 Term: Hepatitis C recurrent System Organ Class: 100000004862
Conditions
Sponsors
Rottapharm
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed and dated informed consent before undergoing any trial-related procedures 2.Male or female patient aged between 18 and 70 years inclusive 3.Patient with documented HCV infection 4.Patient with a documented diagnosis of cirrhosis 5.Patient placed on waiting list for liver transplantation 6.Ability to communicate, participate, and comply with the requirements of the entire study [NB: patients that cannot afford the burden of daily visits to the center to receive the daily treatment before LT or patients with baseline characteristics (e.g. rare ABO and Rh blood groups) causing a low chance to receive a compatible graft within 42 days after randomization are eligible for the post-LT treatment only and can be randomized to Treatment Groups D or E]. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 140 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1.Co-infection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive) 2.Active septic infections at time of screening 3.Previous organ/tissue transplantation other than cornea and hair 4.Patients requiring combined transplantation 5.Use of systemic immunomodulators (including systemic corticosteroids) within 4 weeks of the screening visit or during the screening period 6.Total bilirubin value >10mg/dL [Patients with total bilirubin value >10mg/dL are eligible to receive the post-LT treatment only, and therefore will be randomized to Treatment Groups F or G] 7.Patients not eligible to be treated with ribavirin as per the instructions present in its prescribing information document 8.For females of childbearing potential: -Pregnancy (i.e. positive pregnancy test at screening) or breast feeding -Failure to agree to practice adequate contraception methods (e.g. oral contraceptives, intra-uterine device (IUD), transdermal contraceptive patch). 9.Male patients not vasectomized, who do not agree to abstain from intercourse or who do not use a condom 10.Treatment for HCV with any investigational medication (prior use of silymarin is not exclusionary) 11.Treatment for HCV with any licensed therapies or therapy with any interferon alpha within 30 days of the randomization visit 12.Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study 13.Any known pre-existing medical condition that could interfere with the listing of the patient or with his/her participation in and completion of the study, including but not limited to: -Chronic pulmonary disease (e.g. clinical chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis) -Current or history of any clinically significant cardiac abnormalities/dysfunction (e.g. angina, congestive heart failure, myocardial infarction, pulmonary hypertension, complex congenital heart disease, cardiomyopathy, significant arrhythmia) including current uncontrolled hypertension, or history of use of antianginal agents for cardiac conditions 14.Site personnel directly involved in the study or their family members 15.Known hypersensitivity to Legalon® SIL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if a treatment with Legalon® SIL, alone or in combination with ribavirin, is effective in reducing the Hepatitis C Virus Ribonucleic Acid (HCV-RNA) levels down to undetectable, after Liver Transplantation (LT), in Chronic Hepatitis C patients undergoing LT.;Secondary Objective: -To assess if a treatment with Legalon® SIL, alone or in combination with ribavirin, is effective on histological endpoints -To determine whether Legalon® SIL, alone or in combination with ribavirin, is able to induce other clinically significant virological responses -To assess if a treatment with Legalon® SIL, alone or in combination with ribavirin, is able to improve liver function during pre-LT period -To assess the safety and tolerability of Legalon® SIL, alone or in combination with ribavirin, including its potential effect on immunosuppressant agents -To assess the pharmacokinetics of silibinin hydrogen succinate A and B, silibinin A and B and ribavirin -To asses the liver concentrations of silibinin hydrogen succinate A and B and silibinin A and B -To asses Ex-Vivo plasma protein binding of silibinin hydrogen succinate A and B;Primary end point(s): The primary end-point is Complete Virological Response defined as undetectable HCV-RNA levels at the end of treatment with Legalon® SIL, alone or in combination with a standard dose of ribavirin.;Timepoint(s) of evaluation of this end point: End of treatment with Legalon SIL. For control group 4 weeks after LT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Liver histology evaluation 28 weeks after LT; -Liver fibrosis progression 28 weeks after LT; -Proportion of patients with a Complete Virological Response at end of study treatment, lasting for 4 weeks thereafter ? SVR4 -Proportion of patients with a Complete Virological Response at end of study treatment, lasting for 12 weeks thereafter ? SVR12; -Proportion of patients with a Complete Virological Response at the end of study treatment, lasting for 24 weeks thereafter ? SVR24; -Proportion of patients with a Complete Virological Response at several time points during the course of the study; -Proportion of patients with a Partial Virological Response (at least 2 log10 drop in HCV-RNA) at several time points during the course of the study; -Proportion of patients with virological relapse; -Proportion of patients with virological breakthrough; -Proportion of patients with null response; -Effect of treatment on timing of antiviral therapy institution; -Normalization of Serum Alanine Aminotransferase (ALT) values, compared to baseline, at several time points during the course of the study; -Improvement of Serum Alanine Aminotransferase (ALT) values, compared to baseline, at several time points during the course of the study -Improvement of Liver Function during the pre-LT period Pharmacokinetic Endpoints -Silibinin hydrogen succinate A and B and silibinin A and B plasma concentrations will be determined during the first, the tenth, and the twenty-eighth day of treatment with Legalon® SIL, during both pre-LT and post-LT treatment, until 10h after the start of the infusion. Additional blood samples will be collected during the repeated dosing period, before drug administration. In patients belonging to Groups B, E, and G also RBV red blood cells and plasma concentrations will be determined. Urine concentrations for all drugs will be determined in 0-24h interval. -Silibinin hydrogen succinate A and B and silibinin A and B concentrations will be d | — |
Countries
Spain
Contacts
Public ContactMedical Director
Rottapharm
Outcome results
None listed