Administration of Zepatier (Grazoprevir Plus Elbasvir) in Chronic Hemodialysis (HD) Patients With Hepatitis C

Background - Hepatitis C (HCV) is common in hemodialysis (HD) patients with reported
prevalences of 25%, By 2020, predicted 775,000 hemodialysis patients in the US, of whom
109,000 will have HCV. Hepatitis C is associated with increased mortality in HD patients,
decreased kidney allograft survival, and a source of nosocomial infection in hemodialysis
units. Currently drugs to cure HCV - direct acting antivirals (DAA) which can be safely given
to HD patients are now available. A significant portion of the medical care provided to HD
patients is by Nephrologists and HD staff.

Goals of Protocol - 1. Provide guidelines for implementation and monitoring of DAA therapy in
HD patients with HCV 2. Provide Nephrologists strategies for identification of candidate HD
patients, obtainment of third party approval for DAA payment, specific drug dosing protocols
based on genome type of HCV, and laboratory and clinical monitoring during DDA therapy. 3, By
reducing the pool of HCV patients in a HD Unit, the risk of nosocomial transmission of HCV t
o other patients and staff will be reduced

Study Design - an interventional, prospective, non-randomized, non-blinded trial to evaluate
real world strategies to identify and treat HCV infected patients with Zepatier

Study Procedures 1. Patients who meet inclusion criteria without exclusion criteria be
assigned treatment with Zepatier with or without Ribavirin according to following schedule:
(a) Genotype 1a - treatment naive without NS5A polymorphism - Zepatier one tablet (100 mg
grazoprevir and 50 mg elbasvir) per day for 12 weeks (b) Genotype 1a - treatment naiive with
NS5A polymorphism - Zepatier one tablet daily and ribavirin (200 mg) daily for 16 weeks (c)
Genotype 1b-treatment naive - Zepatier one daily for 12 weeks (d) Genotype 1a or 1b - prior
treatment with INF or HCV NS3/4A protease inhibitor - Zepatier and ribavirin each once daily
for 12 weeks (e) Genotype 4 - treatment naive - Zepatier one daily for 12 weeks (f)Genotype 4
-prior treatment - Zepatier and ribavirin each once per day for 16 weeks

Baseline/Screening Testing: 1. HCV genotype testing 2. HCV viral RNA load 3. Liver function
tests 4, Protime, Partial Thromboplastin time 5. HIV - if positive, then determine viral RNA
and CD4 and T cell count 6. Liver biopsy (within 24 mo of treatment) or Fibroscan within 12
mo of treatment 7. Hepatitis BsAg 8. For patients with HCV genotype 1a, test fro NS5A
mutation

Treatment of HIV/HCV co-infected patients will be done in collaboration with the HIV treating
physician to determine if any adjustments in the HIV drug regimen will be required

Testing/Evaluations during Active DAA Treatment - 1. LFT and RNA HCV viral load at week 4, 8,
and 12. For patients on 16 weeks of treatment, LFT at week 16 as well 2. For patients on
combination Zepatier and ribavirin, hemoglobin monitoring every week during treatment 3.
Clinical pharmacology evaluation for compliance and adverse events at week 4,8,and 12 (and
week 16 for patients on 16 week treatment)

Testing/Evaluation Post DAA Treament - 1, RNA viral load at 12 weeks post treatment 2.
Clinical Pharmacologoy evaluation 12 weeks post treatment for adverse events 3. patients who
achieve sustained viral remission at 12 weeks will be identified in HD records as HCV ab
positive but HCV viral load RNA negative

Inclusion Criteria:

- Hemodialysis patient

- > age 18 years old

- Hepatitis C antibody positive and Hepatitis C RNA Quantification positive

- Hepatitis C genomes 1a, 1b, or 4

- Prior Interferon , ribavirin treatment failures , partial responders, or intolerance
to these treatment allowed to enroll

- Not of reproductive potential - hemodialysis patients must have no menses for 12
months

- Males with partners of reproductive potential as along a 2 reliable forms of
contraception are used simultaneously during treatment and for 6 months after
completion of treatment

- Ability to understand the study procedures, alternative treatments available, risks of
participating in the study, and voluntarily agree to participate

Exclusion Criteria:

- Currently undergoing active treatment for HCV with a direct acting antiviral or have
previously successfully been treated with a direct acting antiviral

- Have moderate or severe hepatic disease - Child-Pugh B or C

- Have evidence of decompensated liver disease manifested by ascites, gastric or
variceal bleeding, hepatic encephalopathy, or other signs/symptoms of advanced liver
disease

- Co-administration of known heaptotoxic drugs including but not limited to : etofoxine,
isoniazid, nitrofurantoin, phenytoin

- Use of strong CYP3A/P-gp inhibitors, organic acid transporting polypeptide 1B1/3
inhibitors, strong inducers of cytochrome 450 3A (CYP3A), efavirenz, or other drugs
which may interact with elbasvir/grazoprevir as per package insert

- history of substance abuse with alcohol, intravenous drugs, psychotropics, narcotics,
cocaine use within 1 year of screening for study

- history of any condition, pre-study lab abnormality, or ECG abnormality or history of
any illness which in the opinion of the investigators might confound the results of
the study or pose additional risks from the administration of elbasvir/grazoprevir

- Have evidence of history of chronic hepatitis not caused by HCV including but not
limited to nonalcoholic steatohepatitis (NASH), drug induced hepatitis, and autoimmune
hepatitis