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

• Grazoprevir plus Elbasvir (Drug): An oral dose of 100 mg/day of grazoprevir as well as an oral dose of 50 mg/day of elbasvir for 12 weeks.

Primary outcomes

• Change of Serum Endostatin Level (ng/mL) From Baseline to 3 Months [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 [3 months]: We evaluated eGFR level at baseline and 3 months after the treatment initiation.

Secondary outcomes

• Sustained Virological Response-12 (SVR12) [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 [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 [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 [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.

Sex: All, ages: 20 Years to any

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.

Participant flow

Outcome results

• Change of Serum Endostatin Level (ng/mL) From Baseline to 3 Months (Primary), Mean, ng/mL: Grazoprevir Plus Elbasvir 156 +/- 58
• Change of eGFR Level (mL/Min/1.73m^2) From Baseline to 3 Months (Primary), Mean, mL/min/1.73m^2: Grazoprevir Plus Elbasvir 52 +/- 8
• Sustained Virological Response-12 (SVR12) (Secondary), Count of participants, Participants: Intention-to-treat Populations 76; Per-protocol Populations 76
• Change of Serum Alanine Aminotransferase (ALT) Level (U/L) From Baseline to 3 Months (Secondary), Mean, U/L: Grazoprevir Plus Elbasvir 47 +/- 41
• Change of Serum Alpha-fetoprotein Level (ng/mL) From Baseline to 3 Months (Secondary), Mean, ng/mL: Grazoprevir Plus Elbasvir 10.7 +/- 17
• Count of Participants With NS3/4A or NS5A Muttations Who Achieved SVR12 (Secondary), Count of participants, Participants: Grazoprevir Plus Elbasvir 15

Adverse events

Time frame: 3 months

Serious adverse events by term

• 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. PMID 23542346
• 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. PMID 27142311
• 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. PMID 26095167

• Study Protocol and Statistical Analysis Plan (PDF, 2018-09-20)

• Norihiro Furusyo, MD, PhD, Principal investigator, Kyushu University Hospital