Hepatitis C Virus RecurrencePhase 2LEG-SIL-LTX-02NCT01518933
Effect of LEGALON SIL on Hepatitis C Virus Recurrence in Stable Liver Transplanted Patients
A Phase 2 study testing Silibinin (Legalon-SIL) and Saline in people with Hepatitis C Virus Recurrence, run by Rottapharm at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C Virus Recurrence
- What is being tested?
- Silibinin (Legalon-SIL) and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Aug 2011to Apr 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Azienda Ospedaliero-Universitaria Policlinico Consorziale
Bari, Bari, 70124
About this study
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
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.
Read the 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.
- Conditions
- Hepatitis C Virus Recurrence
- Being tested
- Silibinin (Legalon-SIL), Saline
- Keywords
- HCV recurrence, stable liver transplanted patients
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Silibinin (Legalon-SIL)Drug
Also called Legalon-SIL, SHS
20 mg/kg Silibinin (Legalon SIL), as per randomization schedule, will be administered daily as a 2-h infusion for 14 days.
SalineDrug
Also called Placebo (saline), as per randomization schedule, will be administered daily as a 2-h infusion for 14 days
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Viral load
To determine the effect of post-transplant treatment with Legalon SIL on HCV viral load 30 days after the beginning of treatment.
Measured: 30 days after the beginning of treatment
Secondary outcomes (3)
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.
Measured: 1 year after the beginning of the treatment
Fibrosis
To determine the effect of post-transplant treatment with Legalon SIL on fibrosis and functional state.
Measured: 1 year after the beginning of the treatment
Safety
To determine the safety and tolerability of post-transplant treatment with Legalon SIL, including evaluation of its effect on the levels of immunomodulators.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2012 (estimated)
- Study startAug 2011
- Primary completionApr 2012
- Study completionApr 2012
Why it stopped: when a blind review highlighted that at least 43% of patients had a virological response
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C Virus RecurrenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rottapharm
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Azienda Ospedaliera Universitaria Policlinico
- Responsible party
- Sponsor
- Investigators
- Alfredo Di Leo, MD, Principal investigator, Azienda Ospedaliero-Universitaria Policlinico Consorziale - Bari
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01518933
- Sponsor's protocol ID
- LEG-SIL-LTX-02
- Acronym
- LEG-SIL-LTX-02
- Status last verified
- Mar 2015
- First submitted
- 23 Jan 2012
- Last updated
- 5 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 24673819
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01518933
- Acronym / sponsor ID
- LEG-SIL-LTX-02 / LEG-SIL-LTX-02
- Conditions
- Hepatitis C Virus Recurrence
- Keywords
- HCV recurrence, stable liver transplanted patients
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: when a blind review highlighted that at least 43% of patients had a virological response
- Enrolment
- 20 participants (actual)
- Lead sponsor
- RottapharmIndustry (pharma, biotech, devices)
- Collaborators
- Azienda Ospedaliera Universitaria Policlinico
- Study start
- Aug 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 26 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Silibilin (Legalon-SIL) | Experimental | Drug: Silibinin (Legalon-SIL)20 mg/kg Silibinin (Legalon SIL) ,as per randomization schedule, will be administered daily as a 2-h infusion for 14 days. |
| Saline | Placebo comparator | Drug: SalinePlacebo (saline), as per randomization schedule, will be administered daily as a 2-h infusion for 14 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Silibinin (Legalon-SIL)Also: Legalon-SIL, SHS20 mg/kg Silibinin (Legalon SIL), as per randomization schedule, will be administered daily as a 2-h infusion for 14 days. | Drug | Silibilin (Legalon-SIL) |
| SalineAlso: Placebo (saline), as per randomization schedule, will be administered daily as a 2-h infusion for 14 daysPlacebo | Drug | Saline |
Primary outcome
Viral load
Time frame: 30 days after the beginning of treatment
To determine the effect of post-transplant treatment with Legalon SIL on HCV viral load 30 days after the beginning of treatment.
3 secondary outcomes
Viral load and lymphocyte activation
Time frame: 1 year after the beginning of the treatment
Fibrosis
Time frame: 1 year after the beginning of the treatment
Safety
Time frame: 1 year
Results and safety
The study was stopped early (reason given: when a blind review highlighted that at least 43% of patients had a virological response). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2015.
- Derived from this study: PubMed 24673819Rendina 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfredo Di Leo, MD principal investigator
Azienda Ospedaliero-Universitaria Policlinico Consorziale - Bari
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Silibinin (Legalon-SIL) and Saline in people with Hepatitis C Virus Recurrence, run by Rottapharm at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: when a blind review highlighted that at least 43% of patients had a virological response). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Viral load (time frame: 30 days after the beginning of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01518933, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2015.