Grazoprevir/Elbasvir for Genotype 1b Chronic Hepatitis C After Liver or Kidney Transplantation

Study Overview
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Brief Summary
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Grazoprevir/elbasvir combination therapy is highly effective in the treatment of genotype 1b chronic hepatitis C, and the drug-drug interaction with central immunosuppressant, such as tacrolimus, should be manageable. The aim of this study is to assess the efficacy and tolerability of grazoprevir/elbasvir combination therapy in treating genotype 1b chronic hepatitis C after liver or kidney transplantation.

Detailed Description
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Grazoprevir/elbasvir combination therapy (grazoprevir 100 mg/ elbasvir 50 mg, Zepatier®, MSD) has been recommended as the 1st-line treatment for genotype 1b chronic hepatitis C by the updated international guidelines, and the rates of sustained virologic response (SVR) can be higher than 95% in either treatment-naïve or peginterferon-experienced patients with genotype 1b chronic hepatitis C. Moreover, even among patients with liver cirrhosis, the efficacy of grazoprevir/elbasvir combination therapy remains very high. In addition, drug-related adverse effects (AEs) were quite low in previous studies, and less than 1% of cirrhotic patients discontinued this therapy during treatment period (4). Grazoprevir/elbasvir combination therapy is an effective and safe treatment for chronic hepatitis C. Chronic hepatitis C is one of the most common indications for liver transplantation. Patients underwent liver or kidney transplantation always suffer from recurrent chronic hepatitis C. Recurrent chronic hepatitis C can result in liver cirrhosis, liver decompensation, and death. Chronic hepatitis C is also associated with a higher incidence of chronic rejection, graft failure and mortality after kidney transplantation. Treating hepatitis C virus (HCV) infection after liver or kidney transplantation was a big challenge before the development of new direct-acting antiviral (DAA). Not only a low SVR rate but also a high rate of severe adverse effects results in the hesitation of peginterferon-ribavirin combination therapy. Although some new DAAs can be used in organ transplantation, the cost remains quite high. More new DAA choices for patients underwent organ transplantation are needed. The clinical data of grazoprevir/elbasvir combination therapy on the treatment for patients with chronic hepatitis C after liver or kidney transplantation remain lacking. With high virologic response rates and low adverse effects in the management for chronic hepatitis C, grazoprevir/elbasvir combination therapy could be a good option for patients underwent liver or kidney transplantation. No drug-drug interaction (DDI) was noted between grazoprevir/elbasvir combination therapy and steroid, and the DDI with the most commonly-used immunosuppressant, tacrolimus, was also not significant, The drug levels of immunosuppressants can be carefully monitored and adjusted during treatment period. The aim of this study is to assess the efficacy and tolerability of grazoprevir/elbasvir combination therapy in treating genotype 1b chronic hepatitis C after liver or kidney transplantation.

Official Title
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An Open-label, Cohort Study of Grazoprevir/Elbasvir Combination Therapy for Patients With Genotype 1b Chronic Hepatitis C After Liver or Kidney Transplantation

Conditions
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Chronic Hepatitis c, Liver Transplant Infection, Kidney Transplant Infection

Intervention / Treatment
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* Drug: grazoprevir 100 mg/ elbasvir 50 mg, Zepatier®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 20 years of age Chronically infected with genotypes 1b HCV Underwent liver and/ or kidney transplantation Without clinical or pathologic evidence of moderate or severe rejection Exclusion Criteria: HCV genotype other than 1b Liver decompensation (Child-Pugh score > 6) Co-infected with human immunodeficiency virus: Positive HIV1/2 or hepatitis B virus : Positive HBsAg and detected HBV DNA Prior exposure to an NS5A inhibitor Any active malignancies Hemoglobin level less than 10 g/dl Platelet level of 75,000/mm3 or less Alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase level 10 times or more the upper limit of normal Total bilirubin level greater than 3 times or more the upper limit of normal Albumin less than 3 g/dL Using medication that is not considered safe to co-administer with , such as cyclosporine Pregnant or breast-feeding women Known allergy to grazoprevir or elbasvir (Unregistered liver or kidney transplant in other countries is illegal in Taiwan)

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Interventional Model Description: grazoprevir 100 mg/ elbasvir 50 mg, Zepatier®, 1# qd for 12 weeks
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zepatier therapy<br>grazoprevir 100 mg/ elbasvir 50 mg (Zepatier®, MSD) once daily for 12 weeks | Drug: grazoprevir 100 mg/ elbasvir 50 mg, Zepatier®<br>* grazoprevir 100 mg/ elbasvir 50 mg (Zepatier®, MSD) once daily for 12 weeks<br>* Other names: Zepatier;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virologic response (SVR) | The HCV viral load (IU/mL) in blood at post-treatment week 12 (SVR12) | At post-treatment week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse effects (AEs) | Any AEs during the treatment period | During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks) | 
| Used immunosuppressant blood levels | The immunosuppressant concentration (ng/mL) in blood during the treatment period | During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks) |