Clinical trial NCT03365635: Administration of Zepatier (Grazoprevir Plus Elbasvir) in Chronic Hemodialysis (HD) Patients With Hepatitis C
Official title: "Real World" Administration of Zepatier (Grazoprevir Plus Elvasvir) in Chronic Hemodialysis Patients With Hepatitis C Infection. Strategies for Identification of Patients, Insurance Approval, Treatment , and Laboratory Monitoring
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C
Hemodialysis
Nosocomial Infection
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-12-07
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: An interventional, prospective, non-randomized, non-blinded trial to evaluate real world strategies to identify and treat hepatitis C infected hemodialysis patients with Zepatier
Primary purpose: TREATMENT

Brief summary: This is a study to define strategies for Nephrologists to directly supervise and apply direct acting antivirals to cure hepatitis C in hemodialysis patients. Strategies will include identification of candidate patients, application for insurance approval, specifics of direct acting antiviral therapy (Zepatier with or without ribavirin) and laboratory monitoring during and after therapy.

Detailed description: 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

Eligibility criteria: 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

Primary outcomes:
measure: SVR - Sustained Virologic Response
timeFrame: 12 weeks after completion of Elbasivir/Grazoprevir treatment
Secondary outcomes:
measure: Approval for DAA by Third Party Payers
timeFrame: Within one month of last patient enrolled
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania Health System
name: Michael R Rudnick, MD
role: PRINCIPAL_INVESTIGATOR
References:
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