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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02946034
• Collaborator: AbbVie (Industry)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 43.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease; Chronic Hepatitis C	Drug: Viekira Pak ± ribavirin; Drug: Mavyret	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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.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)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 1, 2017
• Actual Primary Completion Date: Sep 16, 2020
• Actual Study Completion Date: Sep 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Viekira Pak ± ribavirin or Mavyret 12 week therapy with Viekira Pak ± ribavirin 8 or 12 week therapy with Mavyret	Drug: Viekira Pak ± ribavirin; 12 weeks treatment with AbbVie Viekira Pak ± ribavirin; Other Names: AbbVie 3D regimen ; Drug: Mavyret; 8 or 12 weeks treatment with AbbVie Mavyret

Outcome Measures

Primary Outcome Measures

1. Average Change in Urine Tumor Necrosis Factor (TNF)-Alpha From Baseline to Post-treatment [52 Weeks]

   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.

2. Average Change in Urine Interleukin (IL)-6 From Baseline to Post-treatment [52 weeks]

   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.

3. Average Change in Plasma Tumor Necrosis Factor (TNF)-Alpha From Baseline to Post-treatment [52 weeks]

   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.

4. Average Change in Plasma Interferon Gamma-induced Protein 10 (IP-10) From Baseline to Post-treatment [52 Weeks 52 Weeks 52 weeks]

   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.

5. Average Change in Plasma Interferon (IFN)-Gamma From Baseline to Post-treatment [52 weeks]

   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.

6. Average Change in Plasma Interleukin (IL)-6 From Baseline to Post-treatment [52 weeks]

   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.

Secondary Outcome Measures

1. Number of Patients Who Suffered Adverse Events Related to Study Drug (Safety and Tolerability) [12 weeks]

   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.

2. Number of Patients Who Had Sustained Virologic Response at 12-weeks (SVR12) Post-treatment (Efficacy of Treatment) [24 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female ≥ 18 year of age

2. HCV genotype 1 ≥ 1000 IU/mL

3. 1. Estimated glomerular filtration rate 15-45mL/min/1.73m2 as estimated by CKD-Epi equation

Exclusion Criteria:

1. Pregnant or lactating females

2. Uncontrolled depression or psychiatric disease

3. History or presence of any form of cancer within 3 years of enrollment

4. Experiencing life-threatening cryoglobulinemic vasculitis requiring initiation of rituximab, steroids or plasmapheresis.

5. Uncontrolled cardiovascular or pulmonary disease

6. Experiencing symptoms attributed to uremia

7. Anticipated need to begin renal replacement therapy in the next 6 months

8. History of kidney transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• AbbVie

Investigators

• Principal Investigator: Raymond T Chung, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 25, 2019

More Information

Publications

None provided.

• Responsible Party: Raymond Chung, Director, Hepatology, Massachusetts General Hospital, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02946034
• Other Study ID Numbers: 2016P001822
• First Posted: Oct 26, 2016
• Last Update Posted: Nov 5, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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.: No
• Keywords provided by Raymond Chung, Director, Hepatology, Massachusetts General Hospital, Massachusetts General Hospital: CKD; HCV
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Kidney Diseases; Renal Insufficiency, Chronic; Ribavirin

Study Results

Participant Flow

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients)
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients)
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	10 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	10 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 40%
White	6 60%
More than one race	0 0%
Unknown or Not Reported	0 0%
Hepatitis C genotype (Count of Participants)
Genotype 1a	4 40%
Genotype 1b	2 20%
Genotype 2	1 10%
Genotype 3	2 20%
Genotype 4	1 10%
Baseline estimated glomerular filtration rate (eGFR) (Count of Participants)
60-89 mL/min/1.73m2	1 10%
30-59 mL/min/1.73m2	4 40%
<30 mL/min/1.73m2	5 50%
Hypertension (Count of Participants)
Count of Participants [Participants]	10 100%
Diabetes (Count of Participants)
Count of Participants [Participants]	2 20%

Outcome Measures

1. Primary Outcome

Title	Average Change in Urine Tumor Necrosis Factor (TNF)-Alpha From Baseline to Post-treatment
Description	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.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description

2 patients did not have urine TNF-alpha tested at these timepoints.

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients)
Measure Participants	8
Mean (Standard Deviation) [ng/g]	-0.05 (0.61)

2. Primary Outcome

Title	Average Change in Urine Interleukin (IL)-6 From Baseline to Post-treatment
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

2 patients did not have urine IL-6 tested at these timepoints.

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin 8 or 12 week therapy with Mavyret Viekira Pak ± ribavirin: 12 weeks treatment with AbbVie Viekira Pak ± ribavirin Mavyret: 8 or 12 weeks treatment with AbbVie Mavyret
Measure Participants	8
Mean (Standard Deviation) [ng/g]	5.73 (12.18)

3. Primary Outcome

Title	Average Change in Plasma Tumor Necrosis Factor (TNF)-Alpha From Baseline to Post-treatment
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

2 patients did not have plasma TNF-alpha tested at these timepoints.

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients)
Measure Participants	8
Mean (Standard Deviation) [pg/mL]	6.67 (42.87)

4. Primary Outcome

Title	Average Change in Plasma Interferon Gamma-induced Protein 10 (IP-10) From Baseline to Post-treatment
Description	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.
Time Frame	52 Weeks 52 Weeks 52 weeks

Outcome Measure Data

Analysis Population Description

2 patients did not have plasma IP-10 tested at these timepoints.

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients)
Measure Participants	8
Mean (Standard Deviation) [pg/mL]	-394.57 (657.80)

5. Primary Outcome

Title	Average Change in Plasma Interferon (IFN)-Gamma From Baseline to Post-treatment
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

2 patients did not have plasma IFN-gamma tested at these timepoints.

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients)
Measure Participants	8
Mean (Standard Deviation) [pg/mL]	2.01 (29.57)

6. Primary Outcome

Title	Average Change in Plasma Interleukin (IL)-6 From Baseline to Post-treatment
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

2 patients did not have plasma IL-6 tested at these timepoints.

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients)
Measure Participants	8
Mean (Standard Deviation) [pg/mL]	-3.94 (11)

7. Secondary Outcome

Title	Number of Patients Who Suffered Adverse Events Related to Study Drug (Safety and Tolerability)
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients)
Measure Participants	10
Count of Participants [Participants]	4 40%

8. Secondary Outcome

Title	Number of Patients Who Had Sustained Virologic Response at 12-weeks (SVR12) Post-treatment (Efficacy of Treatment)
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

2 patients did not have hepatitis C checked after 12-weeks post-treatment; thus, we cannot definitively determine that they achieved SVR12.

Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavryet (8 patients)
Measure Participants	8
Count of Participants [Participants]	8 80%

Adverse Events

Time Frame	Each patient was followed for one year after initiation of treatment.
Adverse Event Reporting Description	Adverse events data collection was done at each study visit.
Arm/Group Title	Viekira Pak ± Ribavirin or Mavyret
Arm/Group Description	12 week therapy with Viekira Pak ± ribavirin (2 patients) 8 or 12 week therapy with Mavyret (8 patients
All Cause Mortality
	Viekira Pak ± Ribavirin or Mavyret
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Viekira Pak ± Ribavirin or Mavyret
	Affected / at Risk (%)	# Events
Total	5/10 (50%)
Cardiac disorders
Heart block	1/10 (10%)	1
Hypertensive emergency	1/10 (10%)	1
Gastrointestinal disorders
Abdominal pain	1/10 (10%)	1
Nervous system disorders
Stroke	1/10 (10%)	1
Seizure	1/10 (10%)	1
Fall / loss of consciousness	1/10 (10%)	1
Renal and urinary disorders
Cryoglobulinemic glomerulonephritis	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Viekira Pak ± Ribavirin or Mavyret
	Affected / at Risk (%)	# Events
Total	8/10 (80%)
Blood and lymphatic system disorders
anemia	1/10 (10%)	1
cryoglobulinemia	1/10 (10%)	1
Cardiac disorders
slow ventricular response	1/10 (10%)	2
Musculoskeletal and connective tissue disorders
muscle pain in leg	1/10 (10%)	1
Nervous system disorders
fatigue	3/10 (30%)	3
Renal and urinary disorders
high potassium	1/10 (10%)	1

Limitations/Caveats

Our study has several limitations. Our pilot trial was limited by the small number of patients enrolled. Additionally, two subjects were lost to follow-up, decreasing the power of our analysis comparing pre- and post-treatment kidney function and biomarkers. Thus, the analysis presented is descriptive in nature. The analysis is limited by the absence of a control group.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.