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

March 14, 2021 updated by: Teng-Yu Lee, Taichung Veterans General Hospital

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Taichung, Taiwan
        • China Medical University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sustained virologic response (SVR)
Time Frame: At post-treatment week 12
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)
Time Frame: During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks)
Any AEs during the treatment period
During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks)
Used immunosuppressant blood levels
Time Frame: During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks)
The immunosuppressant concentration (ng/mL) in blood during the treatment period
During the treatment period (the 1st, 2nd, 4th, 6th, 8th, 10th, 12th weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taichung Veterans General Hospital

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Teng-Yu Lee, MD, Taichung Veterans General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 14, 2019

Primary Completion (Actual)

November 30, 2020

Study Completion (Actual)

March 13, 2021

Study Registration Dates

First Submitted

October 26, 2018

First Submitted That Met QC Criteria

October 26, 2018

First Posted (Actual)

October 30, 2018

Study Record Updates

Last Update Posted (Actual)

March 16, 2021

Last Update Submitted That Met QC Criteria

March 14, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SF18281A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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