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

Sponsor

Taichung Veterans General Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT03723824

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Locations

Arm

24.9

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis c Liver Transplant Infection Kidney Transplant Infection	Drug: grazoprevir 100 mg/ elbasvir 50 mg, Zepatier®	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

grazoprevir 100 mg/ elbasvir 50 mg, Zepatier®, 1# qd for 12 weeksgrazoprevir 100 mg/ elbasvir 50 mg, Zepatier®, 1# qd for 12 weeks

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 14, 2019

Actual Primary Completion Date :

Nov 30, 2020

Actual Study Completion Date :

Mar 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zepatier therapy grazoprevir 100 mg/ elbasvir 50 mg (Zepatier®, MSD) once daily for 12 weeks	Drug: grazoprevir 100 mg/ elbasvir 50 mg, Zepatier® grazoprevir 100 mg/ elbasvir 50 mg (Zepatier®, MSD) once daily for 12 weeks Other Names: Zepatier

Arm

Intervention/Treatment

Experimental: Zepatier therapy

grazoprevir 100 mg/ elbasvir 50 mg (Zepatier®, MSD) once daily for 12 weeks

Drug: grazoprevir 100 mg/ elbasvir 50 mg, Zepatier®

grazoprevir 100 mg/ elbasvir 50 mg (Zepatier®, MSD) once daily for 12 weeks

Other Names:

Zepatier

Outcome Measures

Primary Outcome Measures

Sustained virologic response (SVR) [At post-treatment week 12]
The HCV viral load (IU/mL) in blood at post-treatment week 12 (SVR12)

Secondary Outcome Measures

Adverse effects (AEs) [During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks)]
Any AEs during the treatment period
Used immunosuppressant blood levels [During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks)]
The immunosuppressant concentration (ng/mL) in blood during the treatment period

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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