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

November 17, 2021 updated by: Michael Rudnick, University of Pennsylvania

"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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19428
        • Penn Presbyterian Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Genotype 1a -Rx naive -no NS5A polymorph
Genotype 1a - treatment naive without NS5A polymorphism - Drug Intervention : Oral administration Elbasvir (50mg)/Grazoprevir (100mg) one tablet per day for 12 weeks
Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Other Names:
  • Ribavirin 200 mg
Experimental: Genotype 1a, Rx naive + NS5A polymorph
Genotype 1a - treatment naiive with NS5A polymorphism - Oral administration of Elbasvir/Grazoprevir one tablet daily and ribavirin (200 mg) daily for 16 weeks weeks
Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Other Names:
  • Ribavirin 200 mg
Experimental: Genotype 1b - Rx naive
Genotype 1b-treatment naive - Oral administration of Elbasvir/Grazoprevir one daily for 12 weeks
Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Other Names:
  • Ribavirin 200 mg
Experimental: Genotype 1a/1b -prior INF or NS3/4A
Genotype 1a or 1b - prior treatment with INF or HCV NS3/4A protease inhibitor - oral administration of Elbasvir/Grazoprevir and ribavirin each once daily for 12 weeks
Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Other Names:
  • Ribavirin 200 mg
Experimental: Genotype4 - treatment naive
(e) Genotype 4 - treatment naive - oral administration of Elbasvir/Grazoprevir one daily for 12 weeks
Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Other Names:
  • Ribavirin 200 mg
Experimental: Genotype 4- prior treatment
Genotype 4 -prior treatment - oral administration of Elbasvir/Grazoprevir and ribavirin each once per day for 16 weeks
Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Other Names:
  • Ribavirin 200 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SVR - Sustained Virologic Response
Time Frame: 12 weeks after completion of Elbasivir/Grazoprevir treatment
Absence of HCV by viral RNA quantitation at 12 weeks post treatment
12 weeks after completion of Elbasivir/Grazoprevir treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Approval for DAA by Third Party Payers
Time Frame: Within one month of last patient enrolled
The number of participants for whom their third party insurance approved payment of the DAA (study drug)
Within one month of last patient enrolled

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Michael R Rudnick, MD, University of Pennsylvania Health System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 22, 2019

Primary Completion (Actual)

May 1, 2020

Study Completion (Actual)

September 1, 2020

Study Registration Dates

First Submitted

November 29, 2017

First Submitted That Met QC Criteria

December 6, 2017

First Posted (Actual)

December 7, 2017

Study Record Updates

Last Update Posted (Actual)

December 15, 2021

Last Update Submitted That Met QC Criteria

November 17, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 828322

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No research reason to share IPD to other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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