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Pilot Study Evaluate Efficacy of Grazoprevir + Elbasvir for 12 or 16 Weeks in Liver Transplant Recipients. (EGRADICATE)

Primary Purpose

Liver Transplantation, Hepatitis C

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Grazoprevir 100 mg/day
Elbasvir 50 mg/d
Grazoprevir 100 mg/day
Elbasvir 50 mg/day
Ribavirin 1200 mg/day
Sponsored by
Fundacion Clinic per a la Recerca Biomédica
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Transplantation

Eligibility Criteria

18 Years - 78 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age between 18 and 78 year-old.
  • Previous liver transplantation(more than 6 month).
  • Genotype 1 and 4 infection.
  • Hepatitis C recurrence defined by the presence of abnormal liver function test, positive HCV-RNA, histological signs of hepatitis C recurrence.
  • Viral load ≥10000UI/mL.
  • Immunosuppression with tacrolimus and/or mycophenolate (Prednisone use is allowed at low dose, ≤10 mg/d).
  • Treatment naïve or treatment experienced (Peg-RBV or triple therapy).

Exclusion Criteria:

  • Genotype 2, 3, 5 or 6 infection.
  • Decompensated cirrhosis defined by the presence of actual or previous history of clinical decompensation including ascites, hepatic encephalopathy, variceal bleeding or spontaneous bacterial peritonitis, or a Child-Pugh B or C.
  • Hepatocellular carcinoma after liver transplantation.
  • Total bilirubin > 3 mg/dL.
  • Immunosuppression with cyclosporine or an mTOR inhibitor (everolimus or sirolimus).
  • Severe extrahepatic diseases: cardiovascular, respiratory, cerebrovascular and poorly controlled diabetes.
  • Platelets < 75 x 109 cells/L.
  • Neutrophil count < 0.5 x 109 cells/L.
  • Hemoglobin < 9 g/dL.
  • Albumin < 3g/dL.
  • HIV infection.
  • Hepatitis B infection.
  • Active intake of toxic amounts of alcohol or recreational drugs.
  • Females who are pregnant, become to be pregnant or breastfeeding or males whose partners are pregnant, become to be pregnant or breastfeeding.

  • Intake of disallowed medications including(but not limited to):

    1. Antibiotics: clarithromycin, erythromycin, telithromycin, nafcillin, rifampin
    2. Antifungals: itraconazole, ketoconazole, voriconazole
    3. Antihypertensives: nifedipine
    4. Anticonvulsants: carbamazepine, phenytoin, phenobarbital
    5. Bosentan
    6. Modafinil
    7. St.Jonh's Wort
    8. Immunosuppressants: cyclosporin, everolimus, sirolimus
    9. Diabetes agents: glibenclamide, glyburide
    10. Lipid lowering agents: gemfibrozil
    11. Eltrombopag
    12. Lapatinib
    13. HIV medications: efavirenz, etravirine, all ritonavir boosted and unboosted HIV protease inhibitors
    14. Statins: simvastatin, fluvastatin, rosuvastatin at doses greater than 10 mg/d, atorvastatin at doses greater than 10 mg/d.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Genotype 1B

    Genotype 1A and 4

    Arm Description

    treatment 12 weeks

    treatment 16 weeks

    Outcomes

    Primary Outcome Measures

    Sustained virological response
    Sustained virological response 12 w (SVR24) defined as HCV-RNA undetectable at post-treatment week 12.

    Secondary Outcome Measures

    Sustained virological response
    Sustained virological response 12 ( SVR12) defined as HCV-RNA undetectable at post-treatment weeks 4 and , 24 respectively.
    To evaluate the beneficial effects of antiviral therapy on renal function.
    creatinine sample analyses blood analyses in all visits
    To assess the impact of therapy in kidney function.
    Elevation Transaminases blood analyses in all visits
    Tolerability of this combination in liver transplant recipients.
    Serious advers events evaluation

    Full Information

    First Posted
    August 24, 2016
    Last Updated
    November 2, 2017
    Sponsor
    Fundacion Clinic per a la Recerca Biomédica
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02890719
    Brief Title
    Pilot Study Evaluate Efficacy of Grazoprevir + Elbasvir for 12 or 16 Weeks in Liver Transplant Recipients.
    Acronym
    EGRADICATE
    Official Title
    Pilot Study Evaluate Efficacy of Grazoprevir + Elbasvir for 12 or 16 Weeks in Liver Transplant Recipients.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2016
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    impossibility of supplying the medication in research of the study by the pharmaceutical company that gave it to the trial
    Study Start Date
    May 2, 2017 (Actual)
    Primary Completion Date
    June 1, 2017 (Actual)
    Study Completion Date
    December 2017 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Fundacion Clinic per a la Recerca Biomédica

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Pilot, single center, open-label study to evaluate the efficacy and tolerability of Grazoprevir and Elbasvir in HCV GT1 and 4 liver transplant recipients.30 liver transplant recipients with hepatitis C recurrence.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Liver Transplantation, Hepatitis C

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Genotype 1B
    Arm Type
    Experimental
    Arm Description
    treatment 12 weeks
    Arm Title
    Genotype 1A and 4
    Arm Type
    Experimental
    Arm Description
    treatment 16 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Grazoprevir 100 mg/day
    Other Intervention Name(s)
    J05AX68 100 mg
    Intervention Description
    Grazoprevir 100 mg/ day 12 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Elbasvir 50 mg/d
    Other Intervention Name(s)
    J05AX68 50mg
    Intervention Description
    Elbasvir 50 mg/day 12 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Grazoprevir 100 mg/day
    Other Intervention Name(s)
    J05AX68 100 mg
    Intervention Description
    Grazoprevir 100 mg/day 16 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Elbasvir 50 mg/day
    Other Intervention Name(s)
    50mg J05AX68
    Intervention Description
    Elbasvir 50 mg/d 16 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Ribavirin 1200 mg/day
    Other Intervention Name(s)
    J05AB04 1200 mg/d
    Intervention Description
    Ribavirin 1200 mg/day 16 weeks
    Primary Outcome Measure Information:
    Title
    Sustained virological response
    Description
    Sustained virological response 12 w (SVR24) defined as HCV-RNA undetectable at post-treatment week 12.
    Time Frame
    12 weeks post-treatment
    Secondary Outcome Measure Information:
    Title
    Sustained virological response
    Description
    Sustained virological response 12 ( SVR12) defined as HCV-RNA undetectable at post-treatment weeks 4 and , 24 respectively.
    Time Frame
    4 weeks and 24 weeks post-treatment
    Title
    To evaluate the beneficial effects of antiviral therapy on renal function.
    Description
    creatinine sample analyses blood analyses in all visits
    Time Frame
    24 weeks post-treatment
    Title
    To assess the impact of therapy in kidney function.
    Description
    Elevation Transaminases blood analyses in all visits
    Time Frame
    24 weeks post-treatment
    Title
    Tolerability of this combination in liver transplant recipients.
    Description
    Serious advers events evaluation
    Time Frame
    Every visit

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    78 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age between 18 and 78 year-old. Previous liver transplantation(more than 6 month). Genotype 1 and 4 infection. Hepatitis C recurrence defined by the presence of abnormal liver function test, positive HCV-RNA, histological signs of hepatitis C recurrence. Viral load ≥10000UI/mL. Immunosuppression with tacrolimus and/or mycophenolate (Prednisone use is allowed at low dose, ≤10 mg/d). Treatment naïve or treatment experienced (Peg-RBV or triple therapy). Exclusion Criteria: Genotype 2, 3, 5 or 6 infection. Decompensated cirrhosis defined by the presence of actual or previous history of clinical decompensation including ascites, hepatic encephalopathy, variceal bleeding or spontaneous bacterial peritonitis, or a Child-Pugh B or C. Hepatocellular carcinoma after liver transplantation. Total bilirubin > 3 mg/dL. Immunosuppression with cyclosporine or an mTOR inhibitor (everolimus or sirolimus). Severe extrahepatic diseases: cardiovascular, respiratory, cerebrovascular and poorly controlled diabetes. Platelets < 75 x 109 cells/L. Neutrophil count < 0.5 x 109 cells/L. Hemoglobin < 9 g/dL. Albumin < 3g/dL. HIV infection. Hepatitis B infection. Active intake of toxic amounts of alcohol or recreational drugs. Females who are pregnant, become to be pregnant or breastfeeding or males whose partners are pregnant, become to be pregnant or breastfeeding. Intake of disallowed medications including(but not limited to): Antibiotics: clarithromycin, erythromycin, telithromycin, nafcillin, rifampin Antifungals: itraconazole, ketoconazole, voriconazole Antihypertensives: nifedipine Anticonvulsants: carbamazepine, phenytoin, phenobarbital Bosentan Modafinil St.Jonh's Wort Immunosuppressants: cyclosporin, everolimus, sirolimus Diabetes agents: glibenclamide, glyburide Lipid lowering agents: gemfibrozil Eltrombopag Lapatinib HIV medications: efavirenz, etravirine, all ritonavir boosted and unboosted HIV protease inhibitors Statins: simvastatin, fluvastatin, rosuvastatin at doses greater than 10 mg/d, atorvastatin at doses greater than 10 mg/d.

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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