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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease stage3; Hepatitis C Viral
• Intervention / Treatment: Drug: Grazoprevir plus Elbasvir

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital

Participation Criteria

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. Subjects aged 20 years or older.
2. Patients positive for HCV RNA for over 6 months and infected with genotype 1b chronic hepatitis C, including compensated cirrhosis.
3. Patients without co-infection of hepatitis B virus.
4. Patients without co-infection of human immunodeficiency virus
5. 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:

1. Patients with decompensated cirrhosis (Child Pugh B and C)
2. Patients with albumin <3.0 g/dL and platelets <75,000 /μL
3. Patients with autoimmune hepatitis
4. Constant heavy alcohol drinkers (converted to ethanol ≥60 g/day)
5. Patients who have a history of hypersensitivity to grazoprevir and elbasvir
6. Patients who are pregnant females, or females who may become pregnant, or females who are breastfeeding
7. Patients with heart disease that is hard to control (e.g., very recent cardiac infarction, severe heart failure, unstable arrhythmia)
8. Patients who are under medication with drugs listed as contraindication in a package insert of grazoprevir plus elbasvir treatment
9. Patients judged (by the physician in charge of research) to be inappropriate as subjects for the study for any other reasons.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kyushu University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Norihiro Furusyo, MD, PhD, Kyushu University Hospital

Publications and helpful links

General Publications

• Furusyo N, Ogawa E, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, Tanabe Y, Kotoh K, Shimoda S, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group. Telaprevir can be successfully and safely used to treat older patients with genotype 1b chronic hepatitis C. J Hepatol. 2013 Aug;59(2):205-12. doi: 10.1016/j.jhep.2013.03.020. Epub 2013 Mar 28.
• Ogawa E, Furusyo N, Yamashita N, Kawano A, Takahashi K, Dohmen K, Nakamuta M, Satoh T, Nomura H, Azuma K, Koyanagi T, Kotoh K, Shimoda S, Kajiwara E, Hayashi J; Kyushu University Liver Disease Study(KULDS) Group. Effectiveness and safety of daclatasvir plus asunaprevir for patients with hepatitis C virus genotype 1b aged 75 years and over with or without cirrhosis. Hepatol Res. 2017 Mar;47(3):E120-E131. doi: 10.1111/hepr.12738. Epub 2016 Jun 10.
• Ogawa E, Furusyo N, Kajiwara E, Nomura H, Kawano A, Takahashi K, Dohmen K, Satoh T, Azuma K, Nakamuta M, Koyanagi T, Kotoh K, Shimoda S, Hayashi J. Comparative effectiveness and safety study of triple therapy with simeprevir or telaprevir for non-cirrhotic patients with chronic hepatitis C virus genotype 1b infection. J Gastroenterol Hepatol. 2015 Dec;30(12):1759-67. doi: 10.1111/jgh.13016.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): September 20, 2018

Study Registration Dates

• First Submitted: April 28, 2017
• First Submitted That Met QC Criteria: May 4, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): June 3, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Direct Acting Antivirals; Grazoprevir; Elbasvir
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Urologic Diseases; Liver Diseases; Renal Insufficiency; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Kidney Diseases; Renal Insufficiency, Chronic; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Grazoprevir
• Other Study ID Numbers: KULDS-001

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