Chronic Hepatitis CPhase 3NCT00375895
Switch From Tacrolimus to Cyclosporin in the Treatment of Recurrent Hepatitis C After Liver Transplantation
A Phase 3 study testing ciclosporin in people with Chronic Hepatitis C and Evidence of Liver Transplantation, run by Rennes University Hospital at 13 sites in France.
Trial summary
In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation and recurrence causes chronic liver disease in 50 to 80% of cases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C, Evidence of Liver Transplantation
- What is being tested?
- ciclosporin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 13 sitesFrance
- Study dates
- Jun 2006to Dec 2009
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18 or over,
- Who had been included in the Transpeg 1 study,
- Non-responders after a three month peginterferon alfa-2a / ribavirin bitherapy or with a recurrent disease during the Transpeg 1 maintenance phase, whatever the randomization group (ribavirin or placebo),
- With a positive qualitative PCR at inclusion,
- With a METAVIR histologic score of 1 or more on the last biopsy (done within the 6 months preceding inclusion),
- Treated with tacrolimus for at least 6 months prior to inclusion,
- Having given a written informed consent.
Who cannot join
- Treatment with peginterferon or ribavirin within the 6 months preceding inclusion,
- Severe hepatocellular failure or decompensated cirrhosis,
- Acute graft rejection within the two months preceding inclusion, or signs of chronic rejection on the last biopsy, or retransplantation since inclusion in the Transpeg 1 study,
- Treatment with cyclosporin for more than 6 months during the 24 months preceding inclusion,
- Treatment with a mTOR inhibitor or with another investigational immunosuppressive drug,
- Positive serology for HIV or HBV,
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- Cancer (or history of other malignancy during the last 5 years) except patients transplanted for hepatocellular carcinoma and basocellular or excised spinocellular carcinoma,
- Serious concomitant disease or acute or chronic disorder, other than the current transplant, treated with steroids,
- Serious cardiac pathology within the last 6 months,
- Women with ongoing pregnancy or breast-feeding,
- Serious chronic renal failure (creatinine clearance < 30 ml/mn),
- Haemoglobin < 10 g/dl, platelets < 50 000/mm3 or neutrophils < 1000 / mm3,
- Abnormal TSH values,
- Inability to cooperate or to communicate with the investigator,
- Contraindications to ribavirin, peginterferon alfa-2a or cyclosporin.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
France13 sites
Service d'Hépatologie - Hôpital Jean Minjoz
Besançon, 25030
Service d'Hépatogastroentérologie - Hôpital Beaujon
Clichy, 92118
Service d'Hépatologie et Gastroentérologie - CH Henri Mondor
Créteil, 94010
Service des Maladies de l'Appareil Digestif - CHRU Claude Huriez
Lille, 59037
Service de Chirurgie Générale - Hôpital Edouard Herriot
Lyon, 69437
Chirurgie Générale - Hôpital de la Conception
Marseille, 13385
Service d'Hépato-gastro-entérologie - Hôpital Saint Eloi
Montpellier, 34295
Chirurgie Viscérale et Digestive - Hôpital de l'Archet
Nice, 06200
Service de Chirurgie Générale - Hôpital Cochin
Paris, 75679
Service des Maladies du Foie - Hôpital Pontchaillou
Rennes, 35033
Service de Chirurgie Générale et Transplantation Multi-organe - Hôpital de la Hautepierre
Strasbourg, 67098
Service d'Hépato-gastro-entérologie - Hôpital de Rangueil
Toulouse, 31403
Centre Hépato-Biliaire - Hôpital Paul Brousse
Villejuif, 94804
About this study
Official title: Prospective, Open-label, Single Arm Pilot Study Evaluating the Effect on Virological Response of the Switch From Tacrolimus to Cyclosporin Associated With a Peginterferon Alfa-2a / Ribavirin Bitherapy, in Non-responder or With Recurrent VHC+ Disease Liver Transplanted Patients.
In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation and recurrence causes chronic liver disease in 50 to 80% of cases. The aim of this study is to assess the efficacy of cyclosporin on C virological response. Patients included in the Transpeg 1 study and non-responder or with a recurrent disease will be switched from their tacrolimus therapy to cyclosporin, in association with a 1 year peginterferon alfa-2a / ribavirin bitherapy. Efficacy will be assessed by the percentage of patients with a negative qualitative PCR after 19 months of cyclosporin treatment.
Read the detailed description
In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation. A main factor determining the severity of recurrent hepatitis C after transplantation may be immunosuppression. Thus optimization of immunosuppressive regimens might be a key aspect to improve the prognosis of chronic hepatitis C in transplanted patients. The two most frequently used immunosuppressive drugs are cyclosporin and tacrolimus. However, it has been shown that virus replication could be inhibited by cyclosporin, through the blockade of cyclophilins, decreasing hepatitis C viral load and improving liver function. These effects were not found with tacrolimus.
The aim of our study is to assess the efficacy on C virological response of the switch from tacrolimus to cyclosporin associated with a peginterferon alfa-2a / ribavirin bitherapy, in non-responder or with a recurrent VHC+ disease liver transplanted patients.
Patients will receive a 19 month cyclosporin treatment, associated during 12 months with a peginterferon alfa-2a / ribavirin bitherapy. Efficacy will be assessed by the percentage of patients with a negative qualitative PCR after 19 months of cyclosporin treatment.
- Being tested
- ciclosporin
- Keywords
- Cyclosporin, Peginterferon, Ribavirin, Chronic hepatitis C, Liver transplantation
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ciclosporinDrug
Also called CsA, Cyclosporin
ciclosporin administered orally twice a day, at the initial dosing of 2.5 mg/kg/d, adjusted to obtain a C2 concentration of 600 ng/ml associated with the usual ribavirin and PEGinterferon bitherapy.
| Study group | Role | What they receive |
|---|---|---|
| Ciclosporin | Experimental | Not described Receives: Drug: ciclosporin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prolonged virological response
Percentage of patients with a negative qualitative PCR, 19 months after the initiation of cyclosporin treatment.
Measured: 19 months
Secondary outcomes (8)
Virological response 4, 7 and 13 months after the initiation of cyclosporin treatment
Percentage of patient with negative or decreased quantitative PCR
Measured: 4, 7 and 13 months
Histological response: METAVIR score at 19 months
Measured: 19 months
Biological response: liver function at 4, 7, 13 and 19 months
Transaminases, gammaGT, alcalin phosphatase, total bilirubin.
Measured: 4, 7, 13 and 19 months
Incidence of acute or chronic graft rejection at 19 months
Measured: 19 months
Incidence of death, graft loss and retransplantation at 13 and 19 months
Measured: 13 and 19 months
Renal function at 4, 7, 13 and 19 months
Creatinin clearance
Measured: 4, 7, 13 and 19 months
Incidence of treatment discontinuation at 4, 7, 13 and 19 months
Measured: 4, 7, 13 and 19 months
Incidence of adverse events (cancers in particular).
Measured: 19 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2006 (estimated)
- Study startJun 2006
- Primary completionOct 2008
- Study completionDec 2009
Why it stopped: Insufficient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Yvon Calmus, MD, PhD, Principal investigator, Hôpital Cochin, ParisEric Bellissant, MD, PhD, Study chair, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00375895
- Sponsor's protocol ID
- EudraCT 2006-002714-35
- Other IDs
- LOC/06-05, CIC0203/058
- Status last verified
- Mar 2012
- First submitted
- 12 Sep 2006
- Last updated
- 2 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Open-label, Single Arm Pilot Study Evaluating the Effect on Virological Response of the Switch From Tacrolimus to Cyclosporin Associated With a Peginterferon Alfa-2a / Ribavirin Bitherapy, in Non-responder or With Recurrent VHC+ Disease Liver Transplanted Patients.
- ClinicalTrials.gov ID
- NCT00375895
- Acronym / sponsor ID
- EudraCT 2006-002714-35
- Keywords
- Cyclosporin, Peginterferon, Ribavirin, Chronic hepatitis C, Liver transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient enrollment
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jun 2006
- Primary completion
- Oct 2008 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 13 Sep 2006 (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.
In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation and recurrence causes chronic liver disease in 50 to 80% of cases. The aim of this study is to assess the efficacy of cyclosporin on C virological response. Patients included in the Transpeg 1 study and non-responder or with a recurrent disease will be switched from their tacrolimus therapy to cyclosporin, in association with a 1 year peginterferon alfa-2a / ribavirin bitherapy. Efficacy will be assessed by the percentage of patients with a negative qualitative PCR after 19 months of cyclosporin treatment.
Detailed description
In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation. A main factor determining the severity of recurrent hepatitis C after transplantation may be immunosuppression. Thus optimization of immunosuppressive regimens might be a key aspect to improve the prognosis of chronic hepatitis C in transplanted patients. The two most frequently used immunosuppressive drugs are cyclosporin and tacrolimus. However, it has been shown that virus replication could be inhibited by cyclosporin, through the blockade of cyclophilins, decreasing hepatitis C viral load and improving liver function. These effects were not found with tacrolimus.
The aim of our study is to assess the efficacy on C virological response of the switch from tacrolimus to cyclosporin associated with a peginterferon alfa-2a / ribavirin bitherapy, in non-responder or with a recurrent VHC+ disease liver transplanted patients.
Patients will receive a 19 month cyclosporin treatment, associated during 12 months with a peginterferon alfa-2a / ribavirin bitherapy. Efficacy will be assessed by the percentage of patients with a negative qualitative PCR after 19 months of cyclosporin treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ciclosporin | Experimental | Drug: ciclosporin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adults aged 18 or over,
- Who had been included in the Transpeg 1 study,
- Non-responders after a three month peginterferon alfa-2a / ribavirin bitherapy or with a recurrent disease during the Transpeg 1 maintenance phase, whatever the randomization group (ribavirin or placebo),
- With a positive qualitative PCR at inclusion,
- With a METAVIR histologic score of 1 or more on the last biopsy (done within the 6 months preceding inclusion),
Key exclusion criteria (15 listed)
- Treatment with peginterferon or ribavirin within the 6 months preceding inclusion,
- Severe hepatocellular failure or decompensated cirrhosis,
- Acute graft rejection within the two months preceding inclusion, or signs of chronic rejection on the last biopsy, or retransplantation since inclusion in the Transpeg 1 study,
- Treatment with cyclosporin for more than 6 months during the 24 months preceding inclusion,
- Treatment with a mTOR inhibitor or with another investigational immunosuppressive drug,
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 |
|---|---|---|
| ciclosporinAlso: CsA, Cyclosporinciclosporin administered orally twice a day, at the initial dosing of 2.5 mg/kg/d, adjusted to obtain a C2 concentration of 600 ng/ml associated with the usual ribavirin and PEGinterferon bitherapy. | Drug | Ciclosporin |
Primary outcome
Prolonged virological response
Time frame: 19 months
Percentage of patients with a negative qualitative PCR, 19 months after the initiation of cyclosporin treatment.
8 secondary outcomes
Virological response 4, 7 and 13 months after the initiation of cyclosporin treatment
Time frame: 4, 7 and 13 months
Histological response: METAVIR score at 19 months
Time frame: 19 months
Biological response: liver function at 4, 7, 13 and 19 months
Time frame: 4, 7, 13 and 19 months
Incidence of acute or chronic graft rejection at 19 months
Time frame: 19 months
Incidence of death, graft loss and retransplantation at 13 and 19 months
Time frame: 13 and 19 months
Renal function at 4, 7, 13 and 19 months
Time frame: 4, 7, 13 and 19 months
Incidence of treatment discontinuation at 4, 7, 13 and 19 months
Time frame: 4, 7, 13 and 19 months
Incidence of adverse events (cancers in particular).
Time frame: 19 months
Results and safety
The study was stopped early (reason given: Insufficient enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2012.
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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.
Yvon Calmus, MD, PhD principal investigator
Hôpital Cochin, Paris
Eric Bellissant, MD, PhD study chair
Rennes University Hospital
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ciclosporin in people with Chronic Hepatitis C and Evidence of Liver Transplantation, run by Rennes University Hospital at 13 sites in France.
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 15 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 2 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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: Insufficient enrollment). 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?
Prolonged virological response (time frame: 19 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 2 Mar 2012.