A Study for G1b CHC Patients With CKD-3 Treated With Grazoprevir Plus Elbasvir

Study Overview
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Brief Summary
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The regimen using grazoprevir plus elbasvir treatment is promising in Japan, because it may safely be used for the elderly patients with renal dysfunction. Grazoprevir and elbasvir are metabolized in the liver and do not require dose-adjustment for patients with renal dysfunction. However, no data related to efficacy and safety of the grazoprevir plus elbasvir treatment for Japanese elderly patients with renal dysfunction (eGFR<60 mL/min/1.73m2) have been reported. Therefore, physicians are at a loss whether or not to treat the patients with renal dysfunction due to no evidence. The aim of this study is to investigate the improvement of serum endostatin level of Japanese patients with CKD stage 3 after grazoprevir (NS3/4A protease inhibitor) plus elbasvir (NS5A replication complex inhibitor) treatment by a prospective, multicenter cohort study.

Official Title
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A Prospective Multicenter Observational Study for Characterization of Renal Function G1b CHC Patients With CKD-3 Treated With Grazoprevir Plus Elbasvir

Conditions
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Hepatitis C Viral, Chronic Kidney Disease stage3

Intervention / Treatment
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* Drug: Grazoprevir plus Elbasvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 20 years or older. Patients positive for HCV RNA for over 6 months and infected with genotype 1b chronic hepatitis C, including compensated cirrhosis. Patients without co-infection of hepatitis B virus. Patients without co-infection of human immunodeficiency virus Patients with moderate chronic kidney disease (CKD stage 3) (eGFR: 30-59 mL/min/1.73m2). A diagnosis of CKD is only confirmed if repeated eGFR tests for at least 90 days. Exclusion Criteria: Patients with decompensated cirrhosis (Child Pugh B and C) Patients with albumin <3.0 g/dL and platelets <75,000 /μL Patients with autoimmune hepatitis Constant heavy alcohol drinkers (converted to ethanol ≥60 g/day) Patients who have a history of hypersensitivity to grazoprevir and elbasvir Patients who are pregnant females, or females who may become pregnant, or females who are breastfeeding Patients with heart disease that is hard to control (e.g., very recent cardiac infarction, severe heart failure, unstable arrhythmia) Patients who are under medication with drugs listed as contraindication in a package insert of grazoprevir plus elbasvir treatment Patients judged (by the physician in charge of research) to be inappropriate as subjects for the study for any other reasons.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Grazoprevir plus Elbasvir<br>Grazoprevir 100 mg plus Elbasvir 50 mg per day for 12 weeks. | Drug: Grazoprevir plus Elbasvir<br>* An oral dose of 100 mg/day of grazoprevir as well as an oral dose of 50 mg/day of elbasvir for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Serum Endostatin Level (ng/mL) From Baseline to 3 Months | We evaluated the serum endostatin at baseline and 3 months after the treatment initiation. | 3 months | 
| Change of eGFR Level (mL/Min/1.73m^2) From Baseline to 3 Months | We evaluated eGFR level at baseline and 3 months after the treatment initiation. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response-12 (SVR12) | SVR12 was defined as undetectable HCV RNA at week 12 after the end of treatment. | 3 months | 
| Change of Serum Alanine Aminotransferase (ALT) Level (U/L) From Baseline to 3 Months | We evaluated the serum ALT levels at baseline and 3 months after the treatment initiation. | 3 months | 
| Change of Serum Alpha-fetoprotein Level (ng/mL) From Baseline to 3 Months | We evaluated the serum alpha-fetoprotein levels at baseline and 3 months after the treatment initiation. | 3 months | 
| Count of Participants With NS3/4A or NS5A Muttations Who Achieved SVR12 | We identified the NS3/4A or NS5A muttations by direct sequencing at baseline. Among participants who had mutations, we calcualted the rate of SVR12. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Direct Acting Antivirals, Grazoprevir, Elbasvir