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

NCT03365635 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 828322
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C; Hemodialysis; Nosocomial Infection

Outcome Measures

Primary Outcomes (1)

• SVR - Sustained Virologic Response

  Absence of HCV by viral RNA quantitation at 12 weeks post treatment

  12 weeks after completion of Elbasivir/Grazoprevir treatment

Secondary Outcomes (1)

• Approval for DAA by Third Party Payers

  Within one month of last patient enrolled

Study Arms (6)

Genotype 1a -Rx naive -no NS5A polymorph

EXPERIMENTAL

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]

Genotype 1a, Rx naive + NS5A polymorph

EXPERIMENTAL

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]

Genotype 1b - Rx naive

EXPERIMENTAL

Genotype 1b-treatment naive - Oral administration of Elbasvir/Grazoprevir one daily for 12 weeks

Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]

Genotype 1a/1b -prior INF or NS3/4A

EXPERIMENTAL

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]

Genotype4 - treatment naive

EXPERIMENTAL

(e) Genotype 4 - treatment naive - oral administration of Elbasvir/Grazoprevir one daily for 12 weeks

Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]

Genotype 4- prior treatment

EXPERIMENTAL

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]

Interventions

Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier] DRUG

Same as described in arm description

Also known as: Ribavirin 200 mg

Genotype 1a -Rx naive -no NS5A polymorph; Genotype 1a, Rx naive + NS5A polymorph; Genotype 1a/1b -prior INF or NS3/4A; Genotype 1b - Rx naive; Genotype 4- prior treatment; Genotype4 - treatment naive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19428, United States

Location

Related Publications (8)

• Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londono MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45. doi: 10.1016/S0140-6736(15)00349-9. Epub 2015 Oct 5.

  PMID: 26456905 BACKGROUND

• Goodkin DA, Bieber B, Jadoul M, Martin P, Kanda E, Pisoni RL. Mortality, Hospitalization, and Quality of Life among Patients with Hepatitis C Infection on Hemodialysis. Clin J Am Soc Nephrol. 2017 Feb 7;12(2):287-297. doi: 10.2215/CJN.07940716. Epub 2016 Dec 1.

  PMID: 27908905 BACKGROUND

• Zaki MSE. The effect of Hepatitis C Virus infection on cardiovascular complications in end stage kidney disease patients on regular hemodialysis. Electron Physician. 2017 Feb 25;9(2):3857-3861. doi: 10.19082/3857. eCollection 2017 Feb.

  PMID: 28465818 BACKGROUND

• Jadoul M, Horsmans Y. Towards eradication of hepatitis C virus from dialysis units. Lancet. 2015 Oct 17;386(10003):1514-5. doi: 10.1016/S0140-6736(15)00381-5. Epub 2015 Oct 5. No abstract available.

  PMID: 26456906 BACKGROUND

• Lo Re V. Extrahepatic Complications of Hepatitis C Virus Infection in HIV and the Impact of Successful Antiviral Treatment. Clin Infect Dis. 2017 Feb 15;64(4):498-500. doi: 10.1093/cid/ciw814. No abstract available.

  PMID: 28172488 BACKGROUND

• Cacoub P, Desbois AC, Isnard-Bagnis C, Rocatello D, Ferri C. Hepatitis C virus infection and chronic kidney disease: Time for reappraisal. J Hepatol. 2016 Oct;65(1 Suppl):S82-S94. doi: 10.1016/j.jhep.2016.06.011.

  PMID: 27641990 BACKGROUND

• Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl. 2008 Apr;(109):S1-99. doi: 10.1038/ki.2008.81. No abstract available.

  PMID: 18382440 BACKGROUND

• Rao AK, Luckman E, Wise ME, MacCannell T, Blythe D, Lin Y, Xia G, Drobeniuc J, Noble-Wang J, Arduino MJ, Thompson ND, Patel PR, Wilson LE. Outbreak of hepatitis C virus infections at an outpatient hemodialysis facility: the importance of infection control competencies. Nephrol Nurs J. 2013 Mar-Apr;40(2):101-10, 164; quiz 111.

  PMID: 23785746 BACKGROUND

MeSH Terms

Conditions

Hepatitis C; Cross Infection

Interventions

elbasvir; grazoprevir; elbasvir-grazoprevir drug combination; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

We anticipated screening 30 patients and enrolling 25 patients. However, there was a significant delay in the regulatory approvals for the protocol and during this delay period, many of the potential patients ultimately received direct acting antivirals from the primary care physicians or other physicians outside of Nephrology

Results Point of Contact

• Title: Michael R. Rudnick, MD
• Organization: Penn Presbyterian Medical Center

rudnickm@uphs.upenn.edu

215-662-8738

Study Officials

• Michael R Rudnick, MD

  University of Pennsylvania Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: An interventional, prospective, non-randomized, non-blinded trial to evaluate real world strategies to identify and treat hepatitis C infected hemodialysis patients with Zepatier

Study Record Dates

• First Submitted: November 29, 2017
• First Posted: December 7, 2017
• Study Start: September 22, 2019
• Primary Completion: May 1, 2020
• Study Completion: September 1, 2020
• Last Updated: December 15, 2021
• Results First Posted: December 15, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)