A Phase 4 interventional study of Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier] in Hepatitis C, Hemodialysis and Nosocomial Infection, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-12-15.
Sponsored by University of Pennsylvania · Phase 4, Interventional, and Treatment
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.
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
Exclusion Criteria:
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 - 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-treatment naive - Oral administration of Elbasvir/Grazoprevir one daily for 12 weeks
Drug: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
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]
(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 - 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
Also known as: Ribavirin 200 mg
SVR - Sustained Virologic Response
Absence of HCV by viral RNA quantitation at 12 weeks post treatment
Time frame: 12 weeks after completion of Elbasivir/Grazoprevir treatment
Approval for DAA by Third Party Payers
The number of participants for whom their third party insurance approved payment of the DAA (study drug)
Time frame: Within one month of last patient enrolled
Patients from an outpatient hemodialysis unit were recruited between October 2019 and April 2020
| Milestone | Genotype 1a -Rx Naive -no NS5A Polymorph | Genotype 1a, Rx Naive + NS5A Polymorph | Genotype 1b - Rx Naive | Genotype 1a/1b -Prior INF or NS3/4A | Genotype4 - Treatment Naive | Genotype 4- Prior Treatment |
|---|---|---|---|---|---|---|
| Started | 3 | 0 | 1 | 0 | 0 | 0 |
| Completed | 3 | 0 | 1 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 |
Absence of HCV by viral RNA quantitation at 12 weeks post treatment
| Participants | Genotype 1a -Rx Naive -no NS5A Polymorph | Genotype 1a, Rx Naive + NS5A Polymorph | Genotype 1b - Rx Naive | Genotype 1a/1b -Prior INF or NS3/4A | Genotype4 - Treatment Naive | Genotype 4- Prior Treatment |
|---|---|---|---|---|---|---|
| SVR - Sustained Virologic Response | 3 | 0 | 1 | 0 | 0 | — |
The number of participants for whom their third party insurance approved payment of the DAA (study drug)
| Participants | Genotype 1a -Rx Naive -no NS5A Polymorph | Genotype 1a, Rx Naive + NS5A Polymorph | Genotype 1b - Rx Naive | Genotype 1a/1b -Prior INF or NS3/4A | Genotype4 - Treatment Naive | Genotype 4- Prior Treatment |
|---|---|---|---|---|---|---|
| Approval for DAA by Third Party Payers | 0 | — | 0 | — | — | — |
Collected over 24 weeks from start of therapy. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Genotype 1a -Rx Naive -no NS5A Polymorph | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) |
| Genotype 1a, Rx Naive + NS5A Polymorph | — | — | — |
| Genotype 1b - Rx Naive | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| Genotype 1a/1b -Prior INF or NS3/4A | — | — | — |
| Genotype4 - Treatment Naive | — | — | — |
| Genotype 4- Prior Treatment | — | — | — |
Genotype 1a, Rx naive + NS5A polymorph, Genotype 1a/1b - prior INF or NS3/4A, Genotype 4- treatment naive and prior treatment - none of the recruited patients fell into these categories after initial screening
| Age, Categorical(Participants) | Genotype 1a -Rx Naive -no NS5A Polymorph | Genotype 1a, Rx Naive + NS5A Polymorph | Genotype 1b - Rx Naive | Genotype 1a/1b -Prior INF or NS3/4A | Genotype4 - Treatment Naive | Genotype 4- Prior Treatment | Total |
|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | — | 0 | 0 | 0 | 0 | 0 |
| >=65 years | 3 | 0 | 1 | 0 | 0 | 0 | 4 |
| Sex: Female, Male(Participants) | Genotype 1a -Rx Naive -no NS5A Polymorph | Genotype 1a, Rx Naive + NS5A Polymorph | Genotype 1b - Rx Naive | Genotype 1a/1b -Prior INF or NS3/4A | Genotype4 - Treatment Naive | Genotype 4- Prior Treatment | Total |
|---|---|---|---|---|---|---|---|
| Female | 1 | — | 0 | — | — | — | 1 |
| Male | 2 | — | 1 | — | — | — | 3 |
| Race (NIH/OMB)(Participants) | Genotype 1a -Rx Naive -no NS5A Polymorph | Genotype 1a, Rx Naive + NS5A Polymorph | Genotype 1b - Rx Naive | Genotype 1a/1b -Prior INF or NS3/4A | Genotype4 - Treatment Naive | Genotype 4- Prior Treatment | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | — | 0 | — | — | — | 0 |
| Asian | 0 | — | 0 | — | — | — | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | — | 0 | — | — | — | 0 |
| Black or African American | 3 | — | 1 | — | — | — | 4 |
| White | 0 | — | 0 | — | — | — | 0 |
| More than one race | 0 | — | 0 | — | — | — | 0 |
| Unknown or Not Reported | 0 | — | 0 | — | — | — | 0 |
| Region of Enrollment(participants) | Genotype 1a -Rx Naive -no NS5A Polymorph | Genotype 1a, Rx Naive + NS5A Polymorph | Genotype 1b - Rx Naive | Genotype 1a/1b -Prior INF or NS3/4A | Genotype4 - Treatment Naive | Genotype 4- Prior Treatment | Total |
|---|---|---|---|---|---|---|---|
| United States | 3 | — | 1 | — | — | — | 4 |
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