- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01463956
Efficacy of PegInterferon-Ribavirin-Boceprevir Therapy in Patients Infected With G1 HCV With Cirrhosis, Awaiting Liver Transplantation
Pilot Study on the Efficacy of Pegylated Interferon-Ribavirin-Boceprevir Triple Therapy in Patients Infected With Genotype 1 HCV With Cirrhosis and Awaiting Liver Transplantation (ANRS HC 29 BOCEPRETRANSPLANT)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Bordeaux, France, 33601
- Haut-levêque Hospital
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Clichy, France, 92110
- Beaujon Hospital
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Creteil, France, 94010 Cedex
- Henri Mondor Hospital
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Grenoble, France, 38700
- A Michallon Hospital
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Lille, France, 59037 cedex
- Claude Huriez Hospital
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Lyon, France, 69 317 CEDEX
- La Croix-Rousse
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Marseille, France, 13285
- La Conception Hospital
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Montpellier, France, 34090
- Saint-Eloi Hospital
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Nice, France, 06202 cedex 3
- Archet Hospital
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Paris, France, 75013
- La Pitié Salpêtrière Hospital
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Paris, France, 75014
- Cochin Hospital
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Paris, France, 75571 Cedex 12
- Staint Antoine Hospital
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Rennes, France, 35033 cedex 9
- Pontchaillou Hospital
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Strasbourg, France, 67091 Cedex
- Civil Hospital
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Toulouse, France, 31059 cedex
- Purpan Hospital Médecine interne
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Toulouse, France, 31059 cedex
- Purpan Hospital
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Tours, France, 37044
- Trousseau Hospital
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Vandoeuvre Les Nancy, France, 54500
- Nancy Hospital
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Villejuif, France, 94804 cedex
- Paul Brousse Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adult 18 years and older
- Chronic infection with hepatitis C virus proven with positive PCR for more than 6 months
- Viral genotype 1
- Cirrhosis while awaiting liver transplantation
- MELD score < or equal to 18
- With or without hepatocellular carcinoma
- Naive to antiviral C treatment
- Failure on a previous treatment. Failure is defined as the persistence of detectable HCV RNA. The previous HCV failure treatment profile must be able to be documented according to the following terminology:- Relapsing patient: HCV RNA undetectable at the end of treatment, becoming detectable again after the discontinuation of treatment- Breakthrough: increase of viremia of 1 log or more during the treatment - Non-responding patient with partial response: HCV RNA detectable at W24 without ever having been undetectable and with a decrease in HCV RNA ≥ 2 log at W12 - Non-responding patient with nul response: decrease in HCV RNA < 2 log at W12
- No need for prior treatment wash-out
- Negative pregnancy test in women of child-bearing age
- Double method of contraception in men and women of child-bearing age during the entire duration of treatment and the 6 months following its discontinuation
- Free, informed, and written consent (signed on the day of pre-enrollment at the latest and before all exams required by the study)
- Person enrolled in or a beneficiary of a social security/Universal Health Insurance Coverage
- Inclusion approved by the Decision Support Committee
Exclusion Criteria:
- Previous HCV treatment with boceprevir or telaprevir
- Alcohol consumption > 40 g/day
- Toxicomania constituting a barrier for starting therapy according to the opinion of the investigator. Patients included in a methadone or buprenorphine replacement program may be enrolled
- MELD > 18
- Non controlled sepsis
- Platelets < 50,000/mm3
- Neutrophil granulocyte levels < 1000/mm3
- Creatinine clearance < 50 mL/min (MDRD)
- Hb < 10 g/dL
- Uncontrolled psychiatric problems
- Contraindications to boceprevir
- Contraindication to interferon or ribavirin
- Subject with major complications of cirrhosis
- HIV coinfection
- HBV coinfection (unless this is treated effectively with analogues, as proven by undetectable viremia for at least 12 months)
- Other infectious disease underway
- Neoplastic disease other than hepatocellular carcinoma during the previous year, or neoplastic disease for which the prognosis is less than 3 years
- Treatment with immunosuppressors (including corticosteroids), antivirals other than those for the study, except aciclovir
- Consumption of St. John's wort
- Associated treatments including a molecule or substance that could interfere with the pharmacokinetic characteristics of boceprevir
- History of a lactose allergy
- Person participating in another study including an exclusion period that is still underway during pre-enrollment
- So-called vulnerable populations (minors, people under guardianship or protection, or a private individual under protection from making legal or administrative decisions)
- Pregnancy, breast-feeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Boceprevir, Pegylated interferon and Ribavirin
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Boceprevir 200 mg capsules at 2400mg/day (800mg 3 times a day) from week 4 until week 48 or until liver transplant (can be performed from week 16)
Peg-Interferon α-2b by subcutaneous injection, 1.5µg/kg/week, from day 0 until week 48 or until liver transplantation, or Peg-Interferon α-2a by subcutaneous injection, 180 µg, once weekly, from day 0 until week 48 or until liver transplantation
Other Names:
Ribavirin: capsules 200 mg (weight-based daily dose: <65kg, 800 mg; 65-80kg, 1000mg; 81-105kg: 1200mg; >105kg: 1400mg), from day 0 until week 48 or until liver transplantation or, Ribavirin: Tablet Oral, weight-based dose, 1000 mg for subjects weighing below 75 kg or 1200 mg for subjects weighing equal or over75 kg, once daily, from day 0 until week 48 or until liver transplantation
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sustained Virologic Response (SVR) Rate
Time Frame: Week 24 after the discontinuation of antiviral C treatment and at the time of liver transplantation or at the time of liver transplantation
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Evaluation of sustained virologic response to antiviral C treatment depends of time of liver transplantation that can be performed between week 16 and week 96 of the trial:
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Week 24 after the discontinuation of antiviral C treatment and at the time of liver transplantation or at the time of liver transplantation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with adverse events as a measure of safety and tolerability
Time Frame: From week 0 to week 144
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Information on adverse events will be collected by the investigator during medical visits and reported in the CRF.
Adverse events will be classified as: a) Flu-like symptoms b) Musculoskeletal symptoms c) Neurologic symptoms d) Psychiatric symptoms e) Constitutional symptoms
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From week 0 to week 144
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Perceived symptoms
Time Frame: at day 0, week 24, week 48 and every 24 week up liver transplant - post liver transplant: day 0, week 24 and week 48
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Information on symptoms as perceived by the patients will be collected through self-administered questionnaires.
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at day 0, week 24, week 48 and every 24 week up liver transplant - post liver transplant: day 0, week 24 and week 48
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Compliance rate.
Time Frame: week 12, week 24, week 36, week 48, week 72 - after Liver transplant:Day 0
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Treatment compliance will be assesses through a self-administered questionnaire reporting the number of medication doses prescribed and taken by the participants
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week 12, week 24, week 36, week 48, week 72 - after Liver transplant:Day 0
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SVR prognosis factors
Time Frame: Week-4 up week 144
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Participants with undetectable plasma HCV-RNA 24 weeks after treatment cessation and/or liver transplantation will be considered as SVR.
Factors potentially associated with SVR will be studied through a logistic regression analysis.
These factors include demographical (age, gender), virological (baseline viral load), clinical (disease severity measured by MELD score) and genetic factors (IL28B polymorphism: TT, CT, or CC)
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Week-4 up week 144
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The predictive value of on-treatment HCV RNA on SVR
Time Frame: During weeks 1, 4, 5, 6, 7, 8, 12, 16, 20, and 24 (before transplantation)
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Quantitative assessment of HCV RNA during treatment will be performed at weeks 1, 4, 5, 6, 7, 8, 12, 16, 20, and 24 and correlated to SVR
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During weeks 1, 4, 5, 6, 7, 8, 12, 16, 20, and 24 (before transplantation)
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The percentage of virologic failure
Time Frame: week 4 and week 48
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Virological failure is defined as an increase of HCV RNA of at least 1 log IU/mL during treatment, or by the reappearance of positive viremia during treatment, after an initial negative result
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week 4 and week 48
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The percentage of relapse after transplantation
Time Frame: Between week 16 and week 144
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Virological relapse is characterized by an HCV RNA negative at the end of treatment but becoming detectable after cessation of therapy.
The proportion of patients with virological relapse will be determined
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Between week 16 and week 144
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Boceprevir resistant mutations
Time Frame: From week 5 to week 48 or after week 48
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The proportion of patients with emergence of resistant mutations to boceprevir in case of detectable viral load during treatment (from W5) and after the discontinuation of treatment in the event of virologic failure will be assessed
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From week 5 to week 48 or after week 48
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Resistant mutations in plasma and liver samples (both explanted liver and graft)
Time Frame: Week 16 up to week 96
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Week 16 up to week 96
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Sepsis according to Systemic Inflammatory Response System (SIRS) Criteria
Time Frame: From day 0 to week 72
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From day 0 to week 72
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Cirrhosis impairment
Time Frame: From day 0 to week 72
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Cirrhosis impairment will be assessed by studying:
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From day 0 to week 72
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Survival after transplantation
Time Frame: Week 16 up to week 96
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Week 16 up to week 96
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Survival rate within one year after liver transplantation
Time Frame: week 64 up to week 144
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week 64 up to week 144
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The mean time elapsed between registration on the transplantation list and the date of transplantation
Time Frame: Week16 up to week 96
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Week16 up to week 96
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Measurement of the residual plasma concentration (Cres) of ribavirin
Time Frame: at Week 4 and Week 8
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at Week 4 and Week 8
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Area Under the Plasma Concentration Time Curve (AUC) From 0-8h of Boceprevir
Time Frame: At week 16 and at week 24 and if the MELD score has changed by more than three points
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At week 16 and at week 24 and if the MELD score has changed by more than three points
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Maximum Plasma Concentration (Cmax) of Boceprevir
Time Frame: At week 16 and at week 24 and if the MELD score has changed by more than three points
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At week 16 and at week 24 and if the MELD score has changed by more than three points
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Time of Maximum Plasma Concentration (Tmax) of Boceprevir
Time Frame: At week 16 and at week 24 and if the MELD score has changed by more than three points
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At week 16 and at week 24 and if the MELD score has changed by more than three points
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Minimum Plasma Concentration (Cmin) of Boceprevir
Time Frame: At week 16 and at week 24 and if the MELD score has changed by more than three points
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At week 16 and at week 24 and if the MELD score has changed by more than three points
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Correlation study between the presence of an elevated level of IP-10 during triple therapy and the absence of sustained virologic response
Time Frame: From week 4 to week 48
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Plasma aliquots will be performed in all patients of the trial at day 0 before liver transplant and day 0 post liver transplant to measure IP10.
Evaluation will be performed at the end of the trial for all patients recruited.
The association between IP-10 level and SVR will be assessed
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From week 4 to week 48
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Histological severity of HCV recurrence after liver transplantation
Time Frame: At week 20 up to week 100, at week 40 up to week 120, at week 64 up to week 144
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Histological severity will be assessed by the METAVIR score at 1 month (if early recurrence), at 6 months, 1 year after transplantation in case of non-response/relapse before transplantation . Liver transplantation can be performed between week 16 and week 96 |
At week 20 up to week 100, at week 40 up to week 120, at week 64 up to week 144
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Insulin Resistance (HOMA-IR)
Time Frame: At baseline, week 48 and at the last follow-up visit
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At baseline, week 48 and at the last follow-up visit
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Virological Response in participants with and without Insulin Resistance
Time Frame: At week 4, 8, 16, 28 and 48 during therapy
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At week 4, 8, 16, 28 and 48 during therapy
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Relationship between the presence of a polymorphism in the IL28B gene (donor and recipient) and SVR
Time Frame: After week 144
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Whole blood aliquots (DNA bank) will be performed at the Day 0 visit to measure IL28B polymorphism.
Evaluation will be performed at the end of the trial for all patients recruited.
The SVR rate will be compared between the different IL28B phenotypes (CC, CT and TT).
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After week 144
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Relationship between the presence of a polymorphism to the ITPA gene and the onset of hemolytic anemia
Time Frame: After week 144
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Whole blood aliquots (DNA bank) will be performed at the Day 0 visit for ITPA gene measure.
Evaluation will be performed at the end of the trial for all patients recruited.
The proportion of patients with occurrence of hemolytic anemia will be compared according to the ITPA polymorphism
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After week 144
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Didier Samuel, Pr, Hepatobiliary Center of Paul Brousse Hospital. France
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Hepatitis
- Fibrosis
- Hepatitis C
- Liver Cirrhosis
- Liver Cirrhosis, Experimental
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Antineoplastic Agents
- Interferons
- Ribavirin
Other Study ID Numbers
- 2011- 001089 -17
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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