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

Study Overview
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Brief Summary
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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.

Official Title
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Pilot Study Evaluate Efficacy of Grazoprevir + Elbasvir for 12 or 16 Weeks in Liver Transplant Recipients.

Conditions
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Liver Transplantation, Hepatitis C

Intervention / Treatment
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* Drug: Grazoprevir 100 mg/day
* Drug: Elbasvir 50 mg/d
* Drug: Grazoprevir 100 mg/day
* Drug: Elbasvir 50 mg/day
* Drug: Ribavirin 1200 mg/day


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genotype 1B<br>treatment 12 weeks | Drug: Grazoprevir 100 mg/day<br>* Grazoprevir 100 mg/ day 12 weeks<br>* Other names: J05AX68 100 mg;Drug: Elbasvir 50 mg/d<br>* Elbasvir 50 mg/day 12 weeks<br>* Other names: J05AX68 50mg;|
| Experimental: Genotype 1A and 4<br>treatment 16 weeks | Drug: Grazoprevir 100 mg/day<br>* Grazoprevir 100 mg/day 16 weeks<br>* Other names: J05AX68 100 mg;Drug: Elbasvir 50 mg/day<br>* Elbasvir 50 mg/d 16 weeks<br>* Other names: 50mg J05AX68;Drug: Ribavirin 1200 mg/day<br>* Ribavirin 1200 mg/day 16 weeks<br>* Other names: J05AB04 1200 mg/d;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response | Sustained virological response 12 w (SVR24) defined as HCV-RNA undetectable at post-treatment week 12. | 12 weeks post-treatment | 

Secondary Outcome Measures

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