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

NCT01518933 | Terminated Phase 2

• 1 other identifier: LEG-SIL-LTX-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C Virus Recurrence

Keywords

HCV recurrence; stable liver transplanted patients

Outcome Measures

Primary Outcomes (1)

• Viral load

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

  30 days after the beginning of treatment

Secondary Outcomes (3)

• Viral load and lymphocyte activation

  1 year after the beginning of the treatment

• Fibrosis

  1 year after the beginning of the treatment

• Safety

  1 year

Study Arms (2)

Silibilin (Legalon-SIL)

EXPERIMENTAL

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

Drug: Silibinin (Legalon-SIL)

Saline

PLACEBO COMPARATOR

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

Drug: Saline

Interventions

Silibinin (Legalon-SIL) DRUG

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

Also known as: Legalon-SIL, SHS

Silibilin (Legalon-SIL)

Saline DRUG

Placebo

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

Saline

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Rottapharm: lead
• Azienda Ospedaliera Universitaria Policlinico: collaborator

Study Sites (1)

Azienda Ospedaliero-Universitaria Policlinico Consorziale

Bari, Bari, 70124, Italy

Location

Related Publications (1)

• 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.

  PMID: 24673819 DERIVED

MeSH Terms

Interventions

Silybin; Sodium Chloride

Intervention Hierarchy (Ancestors)

Silymarin; Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Alfredo Di Leo, MD

  Azienda Ospedaliero-Universitaria Policlinico Consorziale - Bari

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2012
• First Posted: January 26, 2012
• Study Start: August 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: March 5, 2015

Record last verified: 2015-03

Locations

IT (1)