HCV Treatment Immune Response With Grazoprevir/Elbasvir Before or After Renal Transplant
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|ClinicalTrials.gov Identifier: NCT02902120|
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : November 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Hepatitis C Renal Insufficiency, Chronic Disorder of Transplanted Kidney||Drug: Post-transplant Grazoprevir and Elbasvir||Phase 4|
Hide Detailed Description
The study will be a pilot, prospective, single-center, open-label, non-randomized, non-controlled, parallel clinical trial. 25 HCV genotype 1 infected patients post transplant will be enrolled in the study. Recruitment will be conducted through the renal transplant and nephrology outpatient clinics at the University of Maryland.
The post-transplant cohort will include renal transplant recipients of both living donor and deceased donor organs infected with HCV prior to their transplantation with GFRs <50 with active HCV viremia. These patients will be recruited from the University of Maryland's multidisciplinary transplant nephrology clinic or infectious disease clinic.
Screening All patients will be screened at the Institute of Human Virology (IHV) Clinical Research Unit. At this visit, all patients will have screening labs drawn and a history and physical examination performed. Additional requirements will be genotype testing prior to enrollment, but after transplant and disease staging within 12 months of enrollment by liver biopsy, elastography, or biochemical testing. For those who do not have a genotype or disease staging within the specified time frame, genotyping and elastography will be repeated as part of the study screening work up. Eligibility will be determined based upon these results within 6 weeks of starting the study drugs.
Given the reduced efficacy of this regimen in patients with genotype 1a with the presence of baseline NS5A resistance-associated variants (RAVs), the investigators will screen patients for RAVs in patients with HCV genotype 1a at the time of enrollment. Any patient with genotype 1a HCV found to have NS5A RAVs will undergo 16 weeks of therapy according to current treatment guidelines.
Starting therapy Study drugs will be administered starting on day 0 after a history and physical examination is performed and safety labs are checked. All patients will sign an informed consent as approved by our Institutional Review Board (IRB) prior to administration of study drugs.
Study visits during treatment Patients will be followed every 4 weeks while they are receiving study drugs. HCV viral load (VL), safety labs and hepatic panel will be performed at each of these visits. Patients will also be advised about study adherence and monitored for adverse events.
Safety and adverse event monitoring At each study visit, research nurses will inquire about adverse events that may or may not be related to study drugs. Any unfavorable medical occurrences will be recorded, whether or not considered related to the patient's participation in the research, temporally associated with the patient's participation in the research. Adverse events (AEs) classified as grade 3 or higher will be reported to the IRB and principal investigator. Any grade 3 or 4 AEs and all serious adverse events (SAEs) will be reviewed as they occur by the study team.
Safety labs will also be drawn at these visits. Levels of immunosuppressive agents will also be determined at these visits as appropriate. The need for dose modification of the patient's immunosuppression in the time between visits will be recorded.
End of treatment visit Patients will be seen 12 weeks after starting study drugs (or 16 weeks in the case of genotype 1a patients with baseline NS5A RAVs) for an end of study visit. HCV VL, safety labs and hepatic panel will be performed at this visit. Patients will also be counseled about study adherence and the investigators will inquire about adverse events.
Post treatment follow up visits Patients will be followed every 4 weeks for 12 weeks after they complete treatment. HCV VL, safety labs and a hepatic panel will be performed at these visits.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Host Mechanisms Involved in Achieving SVR Using Grazoprevir and Elbasvir in Treatment of Chronic Hepatitis C in Patients With CKD Before and After Renal Transplantation|
|Actual Study Start Date :||May 1, 2017|
|Estimated Primary Completion Date :||December 31, 2019|
|Estimated Study Completion Date :||July 1, 2020|
This arm will evaluate the treatment of patients with HCV and chronic kidney disease (GFR <50) who have had a kidney transplant using grazoprevir and elbasvir.
Drug: Post-transplant Grazoprevir and Elbasvir
Treatment will be started in the post-transplant patients on day 0 with the combination pill zepatier, containing grazoprevir 100mg/elbasvir 50mg by mouth once daily. The medications will be continued for a total of 12 weeks (16 weeks if resistance mutations, RAVs, are detected)
Other Name: Zepatier
- Change in Interferon-stimulated gene (ISG) expression [ Time Frame: This will be measured at day 0, weeks 2, 4, 8, and 12 (and week 16 for those with resistance mutations) ]The study will involve measuring the change in Interferon-stimulated gene (ISG) expression
- Change in Inducible Protein (IP)-10 levels [ Time Frame: This will be measured at day 0, weeks 2, 4, 8, and 12 (and week 16 for those with resistance mutations) ]The study will involve measuring the change in Inducible Protein (IP-10) levels
- Change in HCV-specific T cell response [ Time Frame: This will be measured at day 0, weeks 2, 4, 8, and 12 (and week 16 for those with resistance mutations) ]The study will involve measuring the change in HCV-specific T cell response
- SVR 12 [ Time Frame: This will be measured at week 24 (or 28 for those with resistance mutations) ]Sustained virologic response (SVR) will be assessed by measuring the HCV viral load 12 weeks after completing treatment
- Safety as assessed by adverse event monitoring, including routine lab work [ Time Frame: This will be measured at day 0, weeks 2, 4, 8, 12 (and 16 if resistance mutations are present) ]Safety will be assessed by adverse event monitoring, including routine lab work
- Kidney function [ Time Frame: This will be measured at post treatment week 12 ]Clinical review using labs and the patient's chart will be performed for change in kidney graft function by worsening creatinine
- Proteinuria [ Time Frame: This will be measured at post treatment week 12 ]Clinical review using labs and the patient's chart will be performed for change in kidney graft function by worsening proteinuria
- Kidney Allograft rejection [ Time Frame: This will be measured at post treatment week 12 ]Clinical review using labs and the patient's chart will be performed for documented episodes of kidney rejection
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02902120
|Contact: Jennifer S Husson, MDemail@example.com|
|Contact: Ilise Marrazzo, RN,BSN,CCRP||410-706-2564||Imarrazzo@ihv.umaryland.edu|
|United States, Maryland|
|University of Maryland Medical Center||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Jennifer Husson, MD 410-706-6973|
|Contact: Ilise Marrazzo, RN 4107062564|
|Principal Investigator:||Jennifer S Husson, MD||University of Maryland School of Medicine, Institute of Human Virology|