Viekira Pak or Mavyret Treatment for Patient With Chronic Kidney Disease and Hepatitis C

Study Overview
=================
Brief Summary
-----------------
Open-label experimental trial of 12 weeks of Viekira Pak treatment ± ribavirin or Mavyret for adults with chronic kidney disease and hepatitis C.

Detailed Description
-----------------
The objective of this study is to evaluate the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (referred to as Viekira Pak) ± ribavirin or Glecaprevir / Pibrentasvir (referred to as Mavyret) for adults with advanced CKD with an estimated glomerular filtration rate (eGFR) less than 45ml/min that are infected with hepatitis C virus (HCV) genotype 1 and to determine the effect of treatment on traditional and novel markers of kidney function and cardiovascular disease risk in patients with advanced CKD. During the course of this prospective, single arm treatment trial, we will measure currently accepted markers of kidney function and novel biomarkers of CKD progression to determine if they improve with eradication of HCV.

Official Title
-----------------
Safety, Efficacy, and Changes in Traditional and Novel Biomarkers of Kidney Function in Patients With Hepatitis C and Advanced Chronic Kidney Disease Treated With Abbvie Viekira Pak or Mavyret Regimen

Conditions
-----------------
Chronic Kidney Disease, Chronic Hepatitis C

Intervention / Treatment
-----------------
* Drug: Viekira Pak ± ribavirin
* Drug: Mavyret


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female ≥ 18 year of age HCV genotype 1 ≥ 1000 IU/mL 6. Estimated glomerular filtration rate 15-45mL/min/1.73m2 as estimated by CKD-Epi equation Exclusion Criteria: Pregnant or lactating females Uncontrolled depression or psychiatric disease History or presence of any form of cancer within 3 years of enrollment Experiencing life-threatening cryoglobulinemic vasculitis requiring initiation of rituximab, steroids or plasmapheresis. Uncontrolled cardiovascular or pulmonary disease Experiencing symptoms attributed to uremia Anticipated need to begin renal replacement therapy in the next 6 months History of kidney transplant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This a single-arm study. Initially, Viekira Pak was available through Abbvie. However, once Mavyret became available, it supplanted Viekira Pak as the study medication.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Viekira Pak ± ribavirin or Mavyret<br>12 week therapy with Viekira Pak ± ribavirin 8 or 12 week therapy with Mavyret | Drug: Viekira Pak ± ribavirin<br>* 12 weeks treatment with AbbVie Viekira Pak ± ribavirin<br>* Other names: AbbVie 3D regimen;Drug: Mavyret<br>* 8 or 12 weeks treatment with AbbVie Mavyret<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Change in Plasma Interleukin (IL)-6 From Baseline to Post-treatment | Measure of novel biomarkers of incident and progressive CKD and liver disease to determine if eradication of HCV infection changes the measures of chronic inflammation associated with progressive end-organ disease. To calculate the average change, the difference between baseline values and the average of 12-weeks post treatment and 40-weeks post treatment were found for each patient. These differences were then averaged, as shown below. | 52 weeks | 
| Average Change in Urine Tumor Necrosis Factor (TNF)-Alpha From Baseline to Post-treatment | Measure of novel biomarkers of incident and progressive CKD and liver disease to determine if eradication of HCV infection changes the measures of chronic inflammation associated with progressive end-organ disease. To calculate the average change, the difference between baseline values and the average of 12-weeks post treatment and 40-weeks post treatment were found for each patient. These differences were then averaged, as shown below. | 52 Weeks | 
| Average Change in Urine Interleukin (IL)-6 From Baseline to Post-treatment | Measure of novel biomarkers of incident and progressive CKD and liver disease to determine if eradication of HCV infection changes the measures of chronic inflammation associated with progressive end-organ disease. To calculate the average change, the difference between baseline values and the average of 12-weeks post treatment and 40-weeks post treatment were found for each patient. These differences were then averaged, as shown below. | 52 weeks | 
| Average Change in Plasma Tumor Necrosis Factor (TNF)-Alpha From Baseline to Post-treatment | Measure of novel biomarkers of incident and progressive CKD and liver disease to determine if eradication of HCV infection changes the measures of chronic inflammation associated with progressive end-organ disease. To calculate the average change, the difference between baseline values and the average of 12-weeks post treatment and 40-weeks post treatment were found for each patient. These differences were then averaged, as shown below. | 52 weeks | 
| Average Change in Plasma Interferon Gamma-induced Protein 10 (IP-10) From Baseline to Post-treatment | Measure of novel biomarkers of incident and progressive CKD and liver disease to determine if eradication of HCV infection changes the measures of chronic inflammation associated with progressive end-organ disease. To calculate the average change, the difference between baseline values and the average of 12-weeks post treatment and 40-weeks post treatment were found for each patient. These differences were then averaged, as shown below. | 52 Weeks 52 Weeks 52 weeks | 
| Average Change in Plasma Interferon (IFN)-Gamma From Baseline to Post-treatment | Measure of novel biomarkers of incident and progressive CKD and liver disease to determine if eradication of HCV infection changes the measures of chronic inflammation associated with progressive end-organ disease. To calculate the average change, the difference between baseline values and the average of 12-weeks post treatment and 40-weeks post treatment were found for each patient. These differences were then averaged, as shown below. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Suffered Adverse Events Related to Study Drug (Safety and Tolerability) | Safety and tolerability of Viekira Pak treatment in CKD patients will be assessed by number of patients who suffered adverse events (serious or otherwise) deemed to be related to study drug. | 12 weeks | 
| Number of Patients Who Had Sustained Virologic Response at 12-weeks (SVR12) Post-treatment (Efficacy of Treatment) | Efficacy will be determined by negative HCV RNA viral load measured during the 12 week treatment period as well as 12 weeks after the last dose. | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CKD, HCV