Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

HCV Treatment Immune Response With Grazoprevir/Elbasvir Before or After Renal Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02902120
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : November 4, 2019
Sponsor:
Information provided by (Responsible Party):
Jennifer Husson, University of Maryland, Baltimore

Tracking Information
First Submitted Date  ICMJE August 19, 2016
First Posted Date  ICMJE September 15, 2016
Last Update Posted Date November 4, 2019
Actual Study Start Date  ICMJE May 1, 2017
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02902120 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2019)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
  • 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 in the post-transplant arm ]
    Clinical review using labs and the patient's chart will be performed for documented episodes of kidney rejection
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE HCV Treatment Immune Response With Grazoprevir/Elbasvir Before or After Renal Transplant
Official Title  ICMJE 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
Brief Summary The purpose of this study is to determine whether patients treated for chronic hepatitis C (HCV) with zepatier (grazoprevir/elbasvir) prior to kidney transplant will have a stronger immune response compared to patients treated after kidney transplant. 25 patients with chronic kidney disease (CKD) and HCV will be treated with zepatier and 25 kidney transplant recipients with chronic kidney disease will be treated with zepatier. Blood markers of immune function will be monitored in both groups to determine their response to therapy.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatitis C
  • Renal Insufficiency, Chronic
  • Disorder of Transplanted Kidney
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Post-transplant
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.
Intervention: Drug: Post-transplant Grazoprevir and Elbasvir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 31, 2019)
25
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2016)
50
Estimated Study Completion Date  ICMJE July 1, 2020
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • At least 18 years of age at the time of screening
  • Have stable renal function for one month (30 days) prior to enrollment
  • Have Chronic HCV infection prior to transplantation with documented HCV viremia ≥ 1,000 IU/ml at screening and either documented HCV Ab positivity or HCV viremia ≥ 1,000 IU/ml at least 6 months prior to enrollment.
  • Documented genotype 1 HCV infection prior to enrollment and after their transplant in the post-transplantation cohort
  • HCV disease staging within 12 months prior to enrollment by liver biopsy, transient elastography, or biochemical testing
  • Be able to give informed consent and comply with study guidelines
  • Women of childbearing age will be required to have a negative pregnancy test at enrollment and use birth control throughout the duration of treatment.

Inclusion Criteria Specific to the Pre-transplant Arm

Patients will either be:

  • On the transplant waiting list followed by the University of Maryland's nephrology clinic or the Baltimore VA's nephrology clinic
  • On chronic hemodialysis not yet on the transplant list and followed in the University's hemodialysis center or in the University's nephrology clinic
  • Have chronic kidney disease with GFR <50

Inclusion Criteria Specific to the Post-transplant Arm

• Patients will have undergone renal transplantation no greater than five years prior to enrollment and will be followed in our University's nephrology and infectious disease clinic. They will all have stable renal function at the time of enrollment.

Exclusion Criteria:

  • Documented positive hepatitis B (HBV) surface antigen, and/or HBV DNA prior to enrollment
  • Any prior exposure to HCV protease inhibitor therapy
  • HIV co-infection if on a protease inhibitor based regimen
  • Increase in creatinine of 15% or greater within one month (30 days) of the screening visit
  • Evidence of hepatocellular carcinoma at the time of enrollment
  • Liver disease caused by an etiology other than HCV
  • F4 or decompensated cirrhotic patients
  • Child Pugh class B or C
  • AST or ALT >350 within 6 months prior to enrollment
  • Albumin < 3g/dL at the time of enrollment
  • Platelet count < 75 at the time of enrollment
  • History of clinically significant allergy or adverse event with protease inhibitors
  • Evidence of the acquisition of HCV at the time of or after transplantation
  • Pregnant or breastfeeding women
  • Cyclosporine; St. John's Wort; Efavirenz; Phenytoin; Carbamazepine; Bosentan; HIV protease inhibitors; modafinil; ketoconazole; or rifampin use within 7 days of enrollment
  • Coadministration of more than 20 mg atorvastatin; 10 mg rosuvastatin; 20 mg of fluvastatin, lovastatin or simvastatin
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer S Husson, MD 410-706-6973 jhusson@ihv.umaryland.edu
Contact: Ilise Marrazzo, RN,BSN,CCRP 410-706-2564 Imarrazzo@ihv.umaryland.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02902120
Other Study ID Numbers  ICMJE HP-00071069
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Jennifer Husson, University of Maryland, Baltimore
Study Sponsor  ICMJE University of Maryland, Baltimore
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jennifer S Husson, MD University of Maryland School of Medicine, Institute of Human Virology
PRS Account University of Maryland, Baltimore
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP