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

Phase 4

Terminated

• Conditions: Chronic Hepatitis c; Liver Transplant Infection; Kidney Transplant Infection
• Interventions: Drug: grazoprevir 100 mg/ elbasvir 50 mg, Zepatier®

• Registration Number: NCT03723824
• Lead Sponsor: Taichung Veterans General Hospital

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.

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 Timeline

• Study First Submitted: 2018-10-26
• Study First Submitted QC: 2018-10-26
• Study First Posted: 2018-10-30
• Study Start: 2019-02-14
• Primary Completion: 2020-11-30
• Status Verified: 2021-03
• Study Completion: 2021-03-13
• Last Update Submitted: 2021-03-14
• Last Update Posted: 2021-03-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

1. At least 20 years of age
2. Chronically infected with genotypes 1b HCV
3. Underwent liver and/ or kidney transplantation
4. Without clinical or pathologic evidence of moderate or severe rejection

Exclusion Criteria

1. HCV genotype other than 1b
2. Liver decompensation (Child-Pugh score > 6)
3. Co-infected with human immunodeficiency virus: Positive HIV1/2 or hepatitis B virus : Positive HBsAg and detected HBV DNA
4. Prior exposure to an NS5A inhibitor
5. Any active malignancies
6. Hemoglobin level less than 10 g/dl
7. Platelet level of 75,000/mm3 or less
8. Alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase level 10 times or more the upper limit of normal
9. Total bilirubin level greater than 3 times or more the upper limit of normal
10. Albumin less than 3 g/dL
11. Using medication that is not considered safe to co-administer with , such as cyclosporine
12. Pregnant or breast-feeding women
13. Known allergy to grazoprevir or elbasvir

(Unregistered liver or kidney transplant in other countries is illegal in Taiwan)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Adverse effects (AEs)	During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks)	Any AEs during the treatment period

Trial Locations

Locations (2)

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan