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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-001089-17 | EudraCT Number |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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Evaluation of efficacy of triple therapy with pegylated interferon, ribavirin, and boceprevir in patients with genotype 1 chronic hepatitis C, who are treatment-naive, have relapsed, or are non-responders with cirrhosis and awaiting liver transplantation, with a MELD score less than or equal to 18
Evaluation of sustained virological response defined as the proportion of patients with undetectable hepatitis C virus RNA 24 weeks after discontinuation of therapy and/or after liver transplantation in patients with genotype 1, who are treatment-naive, have relapsed, or are non-responders with cirrhosis and awaiting liver transplantation, with a MELD score less than or equal to 18
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Boceprevir, Pegylated interferon and Ribavirin | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Boceprevir | Drug | 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) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Sustained Virologic Response (SVR) Rate | 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:
| Week 24 after the discontinuation of antiviral C treatment and at the time of liver transplantation or at the time of liver transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events as a measure of safety and tolerability | 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 | From week 0 to week 144 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Didier Samuel, Pr | Hepatobiliary Center of Paul Brousse Hospital. France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Haut-Lévêque Hospital | Bordeaux | 33601 | France | |||
| Beaujon Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27554134 | Result | Fontaine H, Maynard M, Bouix C, Carrieri MP, Botta-Fridlund D, D'Alteroche L, Conti F, Pageaux GP, Leroy V, Metivier S, Anty R, Durand F, Canva V, Vilotitch A, Lebray P, Alric L, Duvoux C, Petrov-Sanchez V, Beaulieux F, Wellems C, Paul C, Roque-Afonso AM, Roche B, Pradat P, Samuel D, Duclos-Vallee JC; BOCEPRETRANSPLANT study group. Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT). Clin Res Hepatol Gastroenterol. 2017 Feb;41(1):56-65. doi: 10.1016/j.clinre.2016.06.006. Epub 2016 Aug 20. |
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| Peg-Interferon α-2b or Peg-Interferon α-2a | Biological | 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 |
|
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| Ribavirin | Drug | 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 |
|
| Perceived symptoms | Information on symptoms as perceived by the patients will be collected through self-administered questionnaires. | at day 0, week 24, week 48 and every 24 week up liver transplant - post liver transplant: day 0, week 24 and week 48 |
| Compliance rate. | Treatment compliance will be assesses through a self-administered questionnaire reporting the number of medication doses prescribed and taken by the participants | week 12, week 24, week 36, week 48, week 72 - after Liver transplant:Day 0 |
| SVR prognosis factors | 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) | Week-4 up week 144 |
| The predictive value of on-treatment HCV RNA on SVR | 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 | During weeks 1, 4, 5, 6, 7, 8, 12, 16, 20, and 24 (before transplantation) |
| The percentage of virologic failure | 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 | week 4 and week 48 |
| The percentage of relapse after transplantation | 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 | Between week 16 and week 144 |
| Boceprevir resistant mutations | 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 | From week 5 to week 48 or after week 48 |
| Resistant mutations in plasma and liver samples (both explanted liver and graft) | Week 16 up to week 96 |
| Sepsis according to Systemic Inflammatory Response System (SIRS) Criteria | From day 0 to week 72 |
| Cirrhosis impairment | Cirrhosis impairment will be assessed by studying:
| From day 0 to week 72 |
| Survival after transplantation | Week 16 up to week 96 |
| Survival rate within one year after liver transplantation | week 64 up to week 144 |
| The mean time elapsed between registration on the transplantation list and the date of transplantation | Week16 up to week 96 |
| Measurement of the residual plasma concentration (Cres) of ribavirin | at Week 4 and Week 8 |
| Area Under the Plasma Concentration Time Curve (AUC) From 0-8h of Boceprevir | At week 16 and at week 24 and if the MELD score has changed by more than three points |
| Maximum Plasma Concentration (Cmax) of Boceprevir | At week 16 and at week 24 and if the MELD score has changed by more than three points |
| Time of Maximum Plasma Concentration (Tmax) of Boceprevir | At week 16 and at week 24 and if the MELD score has changed by more than three points |
| Minimum Plasma Concentration (Cmin) of Boceprevir | At week 16 and at week 24 and if the MELD score has changed by more than three points |
| Correlation study between the presence of an elevated level of IP-10 during triple therapy and the absence of sustained virologic response | 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 | From week 4 to week 48 |
| Histological severity of HCV recurrence after liver transplantation | 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 |
| Insulin Resistance (HOMA-IR) | At baseline, week 48 and at the last follow-up visit |
| Virological Response in participants with and without Insulin Resistance | At week 4, 8, 16, 28 and 48 during therapy |
| Relationship between the presence of a polymorphism in the IL28B gene (donor and recipient) and SVR | 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). | After week 144 |
| Relationship between the presence of a polymorphism to the ITPA gene and the onset of hemolytic anemia | 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 | After week 144 |
| Clichy |
| 92110 |
| France |
| Henri Mondor Hospital | Créteil | 94010 Cedex | France |
| A Michallon Hospital | Grenoble | 38700 | France |
| Claude Huriez hospital | Lille | 59037 cedex | France |
| La Croix-Rousse | Lyon | 69 317 CEDEX | France |
| La Conception Hospital | Marseille | 13285 | France |
| Saint-Eloi Hospital | Montpellier | 34090 | France |
| Archet Hospital | Nice | 06202 cedex 3 | France |
| La Pitié Salpétrière Hospital | Paris | 75013 | France |
| Cochin Hospital | Paris | 75014 | France |
| Staint Antoine Hospital | Paris | 75571 Cedex 12 | France |
| Pontchaillou Hospital | Rennes | 35033 cedex 9 | France |
| Civil Hospital | Strasbourg | 67091 Cedex | France |
| Purpan Hospital Médecine interne | Toulouse | 31059 cedex | France |
| Purpan Hospital | Toulouse | 31059 cedex | France |
| Trousseau Hospital | Tours | 37044 | France |
| Nancy Hospital | Vandœuvre-lès-Nancy | 54500 | France |
| Paul Brousse Hospital | Villejuif | 94804 cedex | France |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| D008106 | Liver Cirrhosis, Experimental |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008103 | Liver Cirrhosis |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C512204 | N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide |
| C417083 | peginterferon alfa-2b |
| D012254 | Ribavirin |
| ID | Term |
|---|---|
| D012263 | Ribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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