Chronic Kidney Disease, Chronic Hepatitis C
Conditions
Keywords
CKD, HCV
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.
Interventions
DRUGViekira Pak ± ribavirin
12 weeks treatment with AbbVie Viekira Pak ± ribavirin
DRUGMavyret
8 or 12 weeks treatment with AbbVie Mavyret
Sponsors
AbbVie
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥ 18 year of age 2. HCV genotype 1 ≥ 1000 IU/mL 3. 6\. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Viekira Pak ± Ribavirin or Mavyret 12 week therapy with Viekira Pak ± ribavirin (2 patients)
8 or 12 week therapy with Mavyret (8 patients) | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Viekira Pak ± Ribavirin or Mavyret |
|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 8 |
| Baseline estimated glomerular filtration rate (eGFR) 30-59 mL/min/1.73m2 | 4 Participants |
| Baseline estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 | 5 Participants |
| Baseline estimated glomerular filtration rate (eGFR) 60-89 mL/min/1.73m2 | 1 Participants |
| Diabetes | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hepatitis C genotype Genotype 1a | 4 Participants |
| Hepatitis C genotype Genotype 1b | 2 Participants |
| Hepatitis C genotype Genotype 2 | 1 Participants |
| Hepatitis C genotype Genotype 3 | 2 Participants |
| Hepatitis C genotype Genotype 4 | 1 Participants |
| Hypertension | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 8 / 10 |
| serious Total, serious adverse events | 5 / 10 |
Outcome results
Primary
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.
Time frame: 52 Weeks 52 Weeks 52 weeks
Population: 2 patients did not have plasma IP-10 tested at these timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Viekira Pak ± Ribavirin or Mavyret | Average Change in Plasma Interferon Gamma-induced Protein 10 (IP-10) From Baseline to Post-treatment | -394.57 pg/mL | Standard Deviation 657.8 |
Primary
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.
Time frame: 52 weeks
Population: 2 patients did not have plasma IFN-gamma tested at these timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Viekira Pak ± Ribavirin or Mavyret | Average Change in Plasma Interferon (IFN)-Gamma From Baseline to Post-treatment | 2.01 pg/mL | Standard Deviation 29.57 |
Primary
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.
Time frame: 52 weeks
Population: 2 patients did not have plasma IL-6 tested at these timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Viekira Pak ± Ribavirin or Mavyret | Average Change in Plasma Interleukin (IL)-6 From Baseline to Post-treatment | -3.94 pg/mL | Standard Deviation 11 |
Primary
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.
Time frame: 52 weeks
Population: 2 patients did not have plasma TNF-alpha tested at these timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Viekira Pak ± Ribavirin or Mavyret | Average Change in Plasma Tumor Necrosis Factor (TNF)-Alpha From Baseline to Post-treatment | 6.67 pg/mL | Standard Deviation 42.87 |
Primary
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.
Time frame: 52 weeks
Population: 2 patients did not have urine IL-6 tested at these timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Viekira Pak ± Ribavirin or Mavyret | Average Change in Urine Interleukin (IL)-6 From Baseline to Post-treatment | 5.73 ng/g | Standard Deviation 12.18 |
Primary
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.
Time frame: 52 Weeks
Population: 2 patients did not have urine TNF-alpha tested at these timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Viekira Pak ± Ribavirin or Mavyret | Average Change in Urine Tumor Necrosis Factor (TNF)-Alpha From Baseline to Post-treatment | -0.05 ng/g | Standard Deviation 0.61 |
Secondary
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.
Time frame: 24 weeks
Population: 2 patients did not have hepatitis C checked after 12-weeks post-treatment; thus, we cannot definitively determine that they achieved SVR12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Viekira Pak ± Ribavirin or Mavyret | Number of Patients Who Had Sustained Virologic Response at 12-weeks (SVR12) Post-treatment (Efficacy of Treatment) | 8 Participants |
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Viekira Pak ± Ribavirin or Mavyret | Number of Patients Who Suffered Adverse Events Related to Study Drug (Safety and Tolerability) | 4 Participants |