HCV Recurrence After Liver TransplantationPhase 2NCT01535092
Legalon SIL for the Treatment of HCV Recurrence in Liver Transplanted Patients
A Phase 2 study testing Silibinin in people with HCV Recurrence After Liver Transplantation, run by Rottapharm.
Trial summary
Orthotopic liver transplantation (OLT) is the treatment of choice for patients with Hepatitis C Virus (HCV) infection and end-stage liver disease or hepatocellular carcinoma; infection of the graft and hepatitis C recurrence is universal after OLT and recurrent HCV hepatitis often follows an accelerated course after… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HCV Recurrence After Liver Transplantation
- What is being tested?
- Silibinin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- No sites listed yet
- Study dates
- Sep 2010to Nov 2011
- 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
- Patient must provide signed and dated informed consent before undergoing any trial related procedure.
- Patient between 18 and 70 years of age.
- Patient must have documented HCV infection. The HCV-RNA result obtained from the local laboratory at the screening visit must confirm HCV-RNA > 1000 IU/mL.
- Patient must qualify for liver transplantation at the time of Screening according to Model for End stage Liver Disease (MELD) criteria
- Patient must have a documented diagnosis of cirrhosis.
- Patient weigh between 50 kg and 100 kg.
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- 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, intrauterine device, transdermal contraceptive patch) and must have a negative pregnancy urine test at screening.
- HCV Genotype, chest X-ray, ultrasonography and ocular examination (for patients with history of diabetes or hypertension) must be performed within 6 months prior to Screening or between Screening and Day 1. 12-Lead ECG must be performed within 3 months prior to Screening.
Who cannot join
- Patients known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive).
- Active septic infections at time of screening.
- Previous organ transplantation other than cornea and hair.
- Use of systemic immunosuppressant or immunomodulating agents (including systemic corticosteroids) within 4 weeks of the screening visit or during the screening period.
- Treatment for HCV with any investigational medication (prior use of silymarin is not exclusionary)
- Treatment for HCV with any licensed therapies or prior maintenance therapy with any interferon alpha within 30 days of the randomization visit.
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- Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study.
- Any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study including but not limited to:
- Chronic pulmonary disease (eg, clinical chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis).
- Current or history of any clinically significant cardiac abnormalities/dysfunction (eg, 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.
- Any other condition which, in the opinion of a physician-investigator, would make the patient unsuitable for enrollment or could interfere with the subject participating in and completing the study.
- Subjects who are part of the site personnel directly involved with this study or those who are family members of the investigational study staff.
- If female, pregnancy or breast-feeding.
- Known hypersensitivity to Legalon® SIL.
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 of the Graft in Orthotopic Liver Transplant Patients
Orthotopic liver transplantation (OLT) is the treatment of choice for patients with Hepatitis C Virus (HCV) infection and end-stage liver disease or hepatocellular carcinoma; infection of the graft and hepatitis C recurrence is universal after OLT and recurrent HCV hepatitis often follows an accelerated course after OLT, with rapid histological recurrence and cirrhosis. These very poor outcome significantly affect graft and patient survival and reduces the benefit of transplantation for this indication. Therapeutic strategies are not available; high viral load, high prevalence of genotype 1b and need of dose reduction of interferon and ribavirin because of the side effects or intolerance, together with the interference of immunosuppressive drugs, resulted in the vast majority of the patients in failure in obtaining viral eradication.
Recently, Silibinin, has been studied and reported to be capable to act as potent antiviral agent in patients with HCV; it has been used successfully in a protocol of a 14 day intravenous infusion in previous non-responders to peginterferon/ribavirin therapy. In view of his postulated profile of safety, it seems an ideal drug to be used in the setting of HCV recurrent patients after liver transplant.
Read more
Aim of this prospective, randomized, double-blind, placebo-controlled, parallel group study is to determine the therapeutic effect of Legalon SIL in the prevention of HCV reinfection in chronically infected hepatitis C patients after OLT.
Awaiting orthotopic liver transplantation patients affected by HCV will be randomised 3:1 to receive, in addition to their current therapy, silibinin 20mg/kg/day (Legalon SIL) or placebo infused over 2 hours from 14 to 21 consecutive days; in addition, patients will receive treatment with silibinin 20mg/kg/day (Legalon SIL), infused over 2 hours, for 7 days after transplant.
The Primary Efficacy endpoint is to achieve sustained virological response (SVR) while Secondary Efficacy endpoints are to evaluate the virologic response, the percentage of patients who has a decreased of at least 2 log10 the levels of HCV-RNA and the safety of Legalon SIL in this population.
- Being tested
- Silibinin, Placebo
- Keywords
- HCV recurrence, HCV reinfection, Liver transplantation, Legalon SIL, silibinin, viral load
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SilibininDrug
Also called Legalon SIL
20mg/Kg daily by intravenous infusion, for 14-21 days pre-OLT and for 7 days post-OLT
PlaceboDrug
Saline, daily infused for 14-21 days pre-OLT and for 7 days post-OLT
| Study group | Role | What they receive |
|---|---|---|
| silibinin | Experimental | Silibinin 20mg/Kg/day (Legalon SIL) by intravenous infusion for 14-21 days before OLT and for 7 days after OLT Receives: Drug: Silibinin |
| Placebo | Placebo comparator | Placebo (NaCl 0.9% - saline) administered daily by intravenous infusion for 14-21 days before OLT and 7 days after OLT Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained virological response (SVR), defined as Virological Response (undetectable HCV-RNA) that lasts 6 months after the transplant
Measured: 6 months
Secondary outcomes (7)
Virologic response (VR) defined as undetectable HCV RNA
Measured: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
Percentage of patients who has a decreased of at least 2 log10 the levels of HCV-RNA
Measured: at week 4 after OLT
Number of patients with AE
Measured: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
laboratory parameters
Measured: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
blood levels of immunosuppressive drugs
Measured: week 1, 2, 3, 4, 8, 12, 24 after OLT
Vital signs
Measured: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
ECG
Measured: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2012 (estimated)
- Study startSep 2010
- Primary completionOct 2011
- Study completionNov 2011
Why it stopped: when realized that the target 60% of patients with SVR was no more achievable
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCV Recurrence After Liver TransplantationStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rottapharm
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Xavier Forns, Dr, Principal investigator, Hospital Clinic i Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01535092
- Sponsor's protocol ID
- LEG-SIL-LTX-03
- Status last verified
- Feb 2012
- First submitted
- 7 Feb 2012
- Last updated
- 17 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2012. 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 of the Graft in Orthotopic Liver Transplant Patients
- ClinicalTrials.gov ID
- NCT01535092
- Acronym / sponsor ID
- LEG-SIL-LTX-03
- Keywords
- HCV recurrence, HCV reinfection, Liver transplantation, Legalon SIL, silibinin, viral load
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: when realized that the target 60% of patients with SVR was no more achievable
- Enrolment
- 14 participants (actual)
- Lead sponsor
- RottapharmIndustry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Oct 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 17 Feb 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.
Orthotopic liver transplantation (OLT) is the treatment of choice for patients with Hepatitis C Virus (HCV) infection and end-stage liver disease or hepatocellular carcinoma; infection of the graft and hepatitis C recurrence is universal after OLT and recurrent HCV hepatitis often follows an accelerated course after OLT, with rapid histological recurrence and cirrhosis. These very poor outcome significantly affect graft and patient survival and reduces the benefit of transplantation for this indication. Therapeutic strategies are not available; high viral load, high prevalence of genotype 1b and need of dose reduction of interferon and ribavirin because of the side effects or intolerance, together with the interference of immunosuppressive drugs, resulted in the vast majority of the patients in failure in obtaining viral eradication.
Recently, Silibinin, has been studied and reported to be capable to act as potent antiviral agent in patients with HCV; it has been used successfully in a protocol of a 14 day intravenous infusion in previous non-responders to peginterferon/ribavirin therapy. In view of his postulated profile of safety, it seems an ideal drug to be used in the setting of HCV recurrent patients after liver transplant.
Aim of this prospective, randomized, double-blind, placebo-controlled, parallel group study is to determine the therapeutic effect of Legalon SIL in the prevention of HCV reinfection in chronically infected hepatitis C patients after OLT.
Awaiting orthotopic liver transplantation patients affected by HCV will be randomised 3:1 to receive, in addition to their current therapy, silibinin 20mg/kg/day (Legalon SIL) or placebo infused over 2 hours from 14 to 21 consecutive days; in addition, patients will receive treatment with silibinin 20mg/kg/day (Legalon SIL), infused over 2 hours, for 7 days after transplant.
The Primary Efficacy endpoint is to achieve sustained virological response (SVR) while Secondary Efficacy endpoints are to evaluate the virologic response, the percentage of patients who has a decreased of at least 2 log10 the levels of HCV-RNA and the safety of Legalon SIL in this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| silibinin | Experimental | Drug: SilibininSilibinin 20mg/Kg/day (Legalon SIL) by intravenous infusion for 14-21 days before OLT and for 7 days after OLT |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (NaCl 0.9% - saline) administered daily by intravenous infusion for 14-21 days before OLT and 7 days after OLT |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient must provide signed and dated informed consent before undergoing any trial related procedure.
- Patient between 18 and 70 years of age.
- Patient must have documented HCV infection. The HCV-RNA result obtained from the local laboratory at the screening visit must confirm HCV-RNA > 1000 IU/mL.
- Patient must qualify for liver transplantation at the time of Screening according to Model for End stage Liver Disease (MELD) criteria
- Patient must have a documented diagnosis of cirrhosis.
Key exclusion criteria (14 listed)
- Patients known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive).
- Active septic infections at time of screening.
- Previous organ transplantation other than cornea and hair.
- Use of systemic immunosuppressant or immunomodulating agents (including systemic corticosteroids) within 4 weeks of the screening visit or during the screening period.
- Treatment for HCV with any investigational medication (prior use of silymarin is not exclusionary)
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 |
|---|---|---|
| SilibininAlso: Legalon SIL20mg/Kg daily by intravenous infusion, for 14-21 days pre-OLT and for 7 days post-OLT | Drug | silibinin |
| PlaceboSaline, daily infused for 14-21 days pre-OLT and for 7 days post-OLT | Drug | Placebo |
Primary outcome
Sustained virological response (SVR), defined as Virological Response (undetectable HCV-RNA) that lasts 6 months after the transplant
Time frame: 6 months
7 secondary outcomes
Virologic response (VR) defined as undetectable HCV RNA
Time frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
Percentage of patients who has a decreased of at least 2 log10 the levels of HCV-RNA
Time frame: at week 4 after OLT
Number of patients with AE
Time frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
laboratory parameters
Time frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
blood levels of immunosuppressive drugs
Time frame: week 1, 2, 3, 4, 8, 12, 24 after OLT
Vital signs
Time frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
ECG
Time frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT
Results and safety
The study was stopped early (reason given: when realized that the target 60% of patients with SVR was no more achievable). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2012.
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.
Xavier Forns, Dr principal investigator
Hospital Clinic i Barcelona
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Silibinin in people with HCV Recurrence After Liver Transplantation, run by Rottapharm.
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 9 inclusion and 14 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 17 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
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 realized that the target 60% of patients with SVR was no more achievable). 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?
Sustained virological response (SVR), defined as Virological Response (undetectable HCV-RNA) that lasts 6 months after the transplant (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Feb 2012.