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

• ClinicalTrials.gov Identifier: NCT03144635
• Recruitment Status: Completed
• First Posted: May 9, 2017
• Results First Posted: June 3, 2019
• Last Update Posted: June 3, 2019
• Sponsor: Kyushu University
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Norihiro Furusyo, Kyushu University

Tracking Information

• First Submitted Date: April 28, 2017
• First Posted Date: May 9, 2017
• Results First Submitted Date: September 21, 2018
• Results First Posted Date: June 3, 2019
• Last Update Posted Date: June 3, 2019
• Actual Study Start Date: April 1, 2017
• Actual Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 18, 2019)

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

Original Primary Outcome Measures (submitted: May 4, 2017)

• Renal function at 12 weeks after the treatment [ Time Frame: 3 months ]
  Change of serum endostatin level (ng/mL) from baseline
• Renal function at 12 weeks after the treatment [ Time Frame: 3 months ]
  Change of serum eGFR level (mL/min/1.73m^2) from baseline

• Change History: Complete list of historical versions of study NCT03144635 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 18, 2019)

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

Original Secondary Outcome Measures (submitted: May 4, 2017)

• Sustained Virological Response-12 (SVR12) [ Time Frame: 3 months ]
  Serum HCV RNA (logIU/mL) at 12 weeks after the completion of administration
• Biochemical effect [ Time Frame: 6 months ]
  Change of serum alanine aminotransferase (ALT) level (U/L) from baseline
• Biochemical effect [ Time Frame: 6 months ]
  Change of serum alpha-fetoprotein level (ng/mL) from baseline
• Biochemical effect [ Time Frame: 6 months ]
  Change of total cholesterol level (mg/dL) from baseline
• Adverse effects [ Time Frame: 6 months ]
  Rate of discontinuation (%)
• Adverse effects [ Time Frame: 6 months ]
  Rate of ALT abnormality (%)
• Adverse effects [ Time Frame: 6 months ]
  Other important medical events
• Relationship between SVR12 and drug resistance mutations in NS3/4A and NS5A regions of HCV genome [ Time Frame: 3 months ]
  Drug resistance of HCV genome

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hepatitis C Viral
• Chronic Kidney Disease stage3

Intervention

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.

Study Arms

Experimental: Grazoprevir plus Elbasvir

Grazoprevir 100 mg plus Elbasvir 50 mg per day for 12 weeks.

Intervention: Drug: Grazoprevir plus Elbasvir

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 4, 2017): 80
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 20, 2018
• Actual Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03144635
• Other Study ID Numbers: KULDS-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Norihiro Furusyo, Kyushu University
• Study Sponsor: Kyushu University
• Collaborators: Merck Sharp & Dohme Corp.

Investigators

• Principal Investigator: Norihiro Furusyo, MD, PhD; Kyushu University Hospital

• PRS Account: Kyushu University
• Verification Date: February 2019