Chronic Kidney Disease stage3, Hepatitis C Viral
Conditions
Keywords
Direct Acting Antivirals, Grazoprevir, 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.
Interventions
DRUGGrazoprevir 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.
Sponsors
Merck Sharp & Dohme LLC
Kyushu University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Grazoprevir Plus Elbasvir Grazoprevir 100 mg plus Elbasvir 50 mg per day for 12 weeks.
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. | 80 |
| Total | 80 |
Baseline characteristics
| Characteristic | Grazoprevir Plus Elbasvir |
|---|---|
| Age, Continuous | 77 years |
| Alanine aminotransferase | 34 U/L |
| Albumin | 4.0 g/dL |
| alpha-fetoprotein | 4.3 ng/mL |
| Aspartate aminotransferase | 43 U/L |
| Body mass index | 23.3 kg/m^2 |
| Cirrhosis | 31 Participants |
| Gamma-glutamyl transpeptidase | 35 U/L |
| HCV NS5A RAS | 16 Participants |
| HCV RNA level | 6.2 logIU/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 80 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 80 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 32 Participants |
| Treatment Naive | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 80 |
| other Total, other adverse events | 0 / 80 |
| serious Total, serious adverse events | 3 / 80 |
Outcome results
Primary
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.
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Grazoprevir Plus Elbasvir | Change of eGFR Level (mL/Min/1.73m^2) From Baseline to 3 Months | Baseline | 52 mL/min/1.73m^2 | Standard Deviation 8 |
| Grazoprevir Plus Elbasvir | Change of eGFR Level (mL/Min/1.73m^2) From Baseline to 3 Months | 3 months | 53 mL/min/1.73m^2 | Standard Deviation 9 |
Primary
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.
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Grazoprevir Plus Elbasvir | Change of Serum Endostatin Level (ng/mL) From Baseline to 3 Months | Baseline | 156 ng/mL | Standard Deviation 58 |
| Grazoprevir Plus Elbasvir | Change of Serum Endostatin Level (ng/mL) From Baseline to 3 Months | 3 months | 176 ng/mL | Standard Deviation 65 |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Grazoprevir Plus Elbasvir | Change of Serum Alanine Aminotransferase (ALT) Level (U/L) From Baseline to 3 Months | Baseline | 47 U/L | Standard Deviation 41 |
| Grazoprevir Plus Elbasvir | Change of Serum Alanine Aminotransferase (ALT) Level (U/L) From Baseline to 3 Months | 3 months | 21 U/L | Standard Deviation 29 |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Grazoprevir Plus Elbasvir | Change of Serum Alpha-fetoprotein Level (ng/mL) From Baseline to 3 Months | Baseline | 10.7 ng/mL | Standard Deviation 17 |
| Grazoprevir Plus Elbasvir | Change of Serum Alpha-fetoprotein Level (ng/mL) From Baseline to 3 Months | 3 months | 4.6 ng/mL | Standard Deviation 3.7 |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Grazoprevir Plus Elbasvir | Count of Participants With NS3/4A or NS5A Muttations Who Achieved SVR12 | 15 Participants |
Secondary
Sustained Virological Response-12 (SVR12)
SVR12 was defined as undetectable HCV RNA at week 12 after the end of treatment.
Time frame: 3 months
Population: Three patients discontinued treatment due to adverse effects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Grazoprevir Plus Elbasvir | Sustained Virological Response-12 (SVR12) | 76 Participants |
| Per-protocol Populations | Sustained Virological Response-12 (SVR12) | 76 Participants |