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Effect of LEGALON SIL on Hepatitis C Virus Recurrence in Stable Liver Transplanted Patients (LEG-SIL-LTX-02)

Primary Purpose

Hepatitis C Virus Recurrence

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Silibinin (Legalon-SIL)
Saline
Sponsored by
Rottapharm
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C Virus Recurrence focused on measuring HCV recurrence, stable liver transplanted patients

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must provide signed and dated informed consent before undergoing any trial related procedure.
  • Males or females aged ≥ 18 and ≤ 70.
  • Patients with HCV recurrent chronic hepatitis after liver transplantation, not responding to treatment with peginterferon/ribavirin (i.e. the so called standard of care, SOC).
  • Stable (≥ 1 year) liver transplanted patients with HCV recurrence (as indicated by positive serum HCV-RNA, increase in transaminases, signs of graft damage according to HCV recurrence and/or presence of liver fibrosis as assessed by Fibroscan).
  • Patients without biochemical, clinical and/or histological suspicion of rejection.
  • Patients must be able to communicate, participate and comply with the requirements of the entire study.
  • Female patients of child-bearing potential must agree on using a contraceptive method (oral contraceptive, intra-uterine device [IUD], transdermal contraceptive patch) and must have a negative pregnancy test at screening.

Exclusion Criteria:

  • Patients with active hepatocellular carcinoma or other neoplasia (excluding cutaneous carcinoma in view of the high prevalence in the transplanted population).
  • Patients with active biliary tract anomalies.
  • Patients with a rejection episode in the 6 months preceding study inclusion.
  • Patients on active interferon treatment.
  • Female patients who are pregnant or breast-feeding.
  • Patients with clinically significant laboratory abnormalities at screening.
  • Patients with creatinine clearance < 50 ml.
  • Patients with any abnormality on physical examination, vital signs (sitting systolic blood pressure greater than 140 mmHg, sitting diastolic blood pressure greater than 90 mmHg and pulse greater than 80 bpm) and ECG, unless these abnormalities are judged to be not clinically significant by the Investigator (a note about this must be made on the electronic Case Report Form - e-CRF).
  • Patients taking any concomitant medication that is not allowed and that cannot be discontinued for the entire study period.
  • Patients who are already taking other investigational drugs/treatments or have taken part in a clinical study within the previous 3 months or 5 half lives (whichever is longer).
  • Patients with known hypersensitivity to any of the test materials or related compounds.
  • Patients with a history of drug, alcohol or other substance abuse or other factors limiting their ability to co-operate during the study.
  • Patients not available to attend all the test days and investigations as foreseen by the protocol, or unable to understand the aim, procedure or possible hazards of the study.

Sites / Locations

  • Azienda Ospedaliero-Universitaria Policlinico Consorziale

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Silibilin (Legalon-SIL)

Saline

Arm Description

20 mg/kg Silibinin (Legalon SIL) ,as per randomization schedule, will be administered daily as a 2-h infusion for 14 days.

Placebo (saline), as per randomization schedule, will be administered daily as a 2-h infusion for 14 days.

Outcomes

Primary Outcome Measures

Viral load
To determine the effect of post-transplant treatment with Legalon SIL on HCV viral load 30 days after the beginning of treatment.

Secondary Outcome Measures

Viral load and lymphocyte activation
To determine the effect of post-transplant treatment with Legalon SIL on HCV viral load and lymphocyte activation one year after the beginning of treatment.
Fibrosis
To determine the effect of post-transplant treatment with Legalon SIL on fibrosis and functional state.
Safety
To determine the safety and tolerability of post-transplant treatment with Legalon SIL, including evaluation of its effect on the levels of immunomodulators.

Full Information

First Posted
January 23, 2012
Last Updated
March 4, 2015
Sponsor
Rottapharm
Collaborators
Azienda Ospedaliera Universitaria Policlinico
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1. Study Identification

Unique Protocol Identification Number
NCT01518933
Brief Title
Effect of LEGALON SIL on Hepatitis C Virus Recurrence in Stable Liver Transplanted Patients
Acronym
LEG-SIL-LTX-02
Official Title
A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of LEGALON SIL for the Treatment of HCV Recurrence in Stable Liver Transplanted Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Terminated
Why Stopped
when a blind review highlighted that at least 43% of patients had a virological response
Study Start Date
August 2011 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rottapharm
Collaborators
Azienda Ospedaliera Universitaria Policlinico

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Hepatitis C virus (HCV)-related liver disease is the most common indication for liver transplantation (LT). However, LT does not cure the infection, and therapeutic strategies resulted in very limited efficacy and tolerability in LT recipients. In view of its postulated safety profile, Silibinin seems an ideal drug to be used in the setting of HCV recurrent patients after liver transplantation.
Detailed Description
Hepatitis C virus (HCV)-related liver disease continues to be the most common indication for liver transplantation (LT) in both the United States and Europe. However, LT does not cure the infection, and re-infection of the liver allograft universally occurs. Recurrent HCV hepatitis often follows an accelerated course after LT, and histological recurrence occurs in approximately 50% of patients within 1 year after LT; 15-30% of them develop cirrhosis within 5 years. In this context, a peculiar feature is represented by the rapid course of liver fibrosis. Therapeutic strategies for managing the primary cause of liver damage, i.e. HCV infection, irrespective of application in pre-, peri-, and/or post-LT periods resulted in very limited efficacy and tolerability in LT recipients. In view of its postulated safety profile, Silibinin seems an ideal drug to be used in the setting of HCV recurrent patients after liver transplantation. Silibinin, a flavonolignan representing the main component (60%) of Silymarin and proposed as an anti-hepatotoxic agent for the treatment of various liver diseases has been recently reported to beneficially modulate the pro-fibrogenic potential of HSC, thus representing a very attractive possibility in the transplanted population. Besides the anti-inflammatory properties, Silibinin is able to inhibit Tumor necrosis factor-alpha (TNF-α). This is a proinflammatory cytokine with a major role in both acute and chronic viral, bacterial and fungal infections. The primary objective is to determine the effect of post-transplant treatment with Legalon SIL on HCV viral load 30 days after the beginning of treatment. 44 stable liver transplanted patients with HCV recurrence will be randomized 3:1 to receive Legalon-SIL or Placebo. Randomized patients will be treated for 14 consecutive days with Legalon-SIL or Placebo. Patients dropping-out before the end of treatment period will be replaced. Patients will be followed up for 1 year to monitor the effect of treatment on liver fibrosis, liver functional state, lymphocyte activation, and viral load.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus Recurrence
Keywords
HCV recurrence, stable liver transplanted patients

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Silibilin (Legalon-SIL)
Arm Type
Experimental
Arm Description
20 mg/kg Silibinin (Legalon SIL) ,as per randomization schedule, will be administered daily as a 2-h infusion for 14 days.
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
Placebo (saline), as per randomization schedule, will be administered daily as a 2-h infusion for 14 days.
Intervention Type
Drug
Intervention Name(s)
Silibinin (Legalon-SIL)
Other Intervention Name(s)
Legalon-SIL, SHS
Intervention Description
20 mg/kg Silibinin (Legalon SIL), as per randomization schedule, will be administered daily as a 2-h infusion for 14 days.
Intervention Type
Drug
Intervention Name(s)
Saline
Other Intervention Name(s)
Placebo (saline), as per randomization schedule, will be administered daily as a 2-h infusion for 14 days
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Viral load
Description
To determine the effect of post-transplant treatment with Legalon SIL on HCV viral load 30 days after the beginning of treatment.
Time Frame
30 days after the beginning of treatment
Secondary Outcome Measure Information:
Title
Viral load and lymphocyte activation
Description
To determine the effect of post-transplant treatment with Legalon SIL on HCV viral load and lymphocyte activation one year after the beginning of treatment.
Time Frame
1 year after the beginning of the treatment
Title
Fibrosis
Description
To determine the effect of post-transplant treatment with Legalon SIL on fibrosis and functional state.
Time Frame
1 year after the beginning of the treatment
Title
Safety
Description
To determine the safety and tolerability of post-transplant treatment with Legalon SIL, including evaluation of its effect on the levels of immunomodulators.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must provide signed and dated informed consent before undergoing any trial related procedure. Males or females aged ≥ 18 and ≤ 70. Patients with HCV recurrent chronic hepatitis after liver transplantation, not responding to treatment with peginterferon/ribavirin (i.e. the so called standard of care, SOC). Stable (≥ 1 year) liver transplanted patients with HCV recurrence (as indicated by positive serum HCV-RNA, increase in transaminases, signs of graft damage according to HCV recurrence and/or presence of liver fibrosis as assessed by Fibroscan). Patients without biochemical, clinical and/or histological suspicion of rejection. Patients must be able to communicate, participate and comply with the requirements of the entire study. Female patients of child-bearing potential must agree on using a contraceptive method (oral contraceptive, intra-uterine device [IUD], transdermal contraceptive patch) and must have a negative pregnancy test at screening. Exclusion Criteria: Patients with active hepatocellular carcinoma or other neoplasia (excluding cutaneous carcinoma in view of the high prevalence in the transplanted population). Patients with active biliary tract anomalies. Patients with a rejection episode in the 6 months preceding study inclusion. Patients on active interferon treatment. Female patients who are pregnant or breast-feeding. Patients with clinically significant laboratory abnormalities at screening. Patients with creatinine clearance < 50 ml. Patients with any abnormality on physical examination, vital signs (sitting systolic blood pressure greater than 140 mmHg, sitting diastolic blood pressure greater than 90 mmHg and pulse greater than 80 bpm) and ECG, unless these abnormalities are judged to be not clinically significant by the Investigator (a note about this must be made on the electronic Case Report Form - e-CRF). Patients taking any concomitant medication that is not allowed and that cannot be discontinued for the entire study period. Patients who are already taking other investigational drugs/treatments or have taken part in a clinical study within the previous 3 months or 5 half lives (whichever is longer). Patients with known hypersensitivity to any of the test materials or related compounds. Patients with a history of drug, alcohol or other substance abuse or other factors limiting their ability to co-operate during the study. Patients not available to attend all the test days and investigations as foreseen by the protocol, or unable to understand the aim, procedure or possible hazards of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alfredo Di Leo, MD
Organizational Affiliation
Azienda Ospedaliero-Universitaria Policlinico Consorziale - Bari
Official's Role
Principal Investigator
Facility Information:
Facility Name
Azienda Ospedaliero-Universitaria Policlinico Consorziale
City
Bari
ZIP/Postal Code
70124
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
24673819
Citation
Rendina M, D'Amato M, Castellaneta A, Castellaneta NM, Brambilla N, Giacovelli G, Rovati L, Rizzi SF, Zappimbulso M, Bringiotti RS, Di Leo A. Antiviral activity and safety profile of silibinin in HCV patients with advanced fibrosis after liver transplantation: a randomized clinical trial. Transpl Int. 2014 Jul;27(7):696-704. doi: 10.1111/tri.12324. Epub 2014 May 10.
Results Reference
derived

Learn more about this trial

Effect of LEGALON SIL on Hepatitis C Virus Recurrence in Stable Liver Transplanted Patients

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