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

NCT02902120 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: HP-00071069
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C; Renal Insufficiency, Chronic; Disorder of Transplanted Kidney

Outcome Measures

Primary Outcomes (1)

• SVR 12

  Sustained virologic response (SVR) will be assessed by measuring the quantitative HCV viral load 12 weeks after completing treatment. This will be a measure of circulating HCV virus in participants off therapy, 12 weeks after finishing treatment, to determine the durability of the response to the treatment.

  This will be measured at post-treatment week 12 (study week 24 or week 28 for those with resistance mutations)

Secondary Outcomes (6)

• Change in T Cell Response

  This will be collected at day 0, week 4, and week 12

• Change in T Cell Immunophenotypes

  This will be collected at day 0, week 4, and week 12

• Quantification of Antiviral Cytokines

  This will be collected at day 0 and week 4

• Safety as Assessed by Adverse Event Monitoring, Including Routine Lab Work

  This will be measured at day 0, weeks 2, 4, 8, 12 (and 16 if resistance mutations are present)

• Kidney Function

  This will be measured at day 0, treatment week 2, treatment week 4, treatment week 8, treatment week 12, ( treatment week 16, if applicable), post-treatment week 4 (week 16/20), and post-treatment week 12 (week 24/28)

Study Arms (1)

Post-transplant

EXPERIMENTAL

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

Interventions

Post-transplant Grazoprevir and Elbasvir DRUG

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)

Also known as: Zepatier

Post-transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Hepatitis C; Renal Insufficiency, Chronic

Interventions

elbasvir; elbasvir-grazoprevir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Lydia Tang
• Organization: Institute of Human Virology, University of Maryland School of Medicine

LydiaTang@ihv.umaryland.edu

410-706-6567

Study Officials

• Jennifer S Husson, MD

  University of Maryland School of Medicine, Institute of Human Virology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: September 15, 2016
• Study Start: May 1, 2017
• Primary Completion: September 1, 2021
• Study Completion: June 8, 2022
• Last Updated: April 22, 2024
• Results First Posted: November 18, 2022

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available immediately upon publication for a duration of 5 years following publication.
• Access Criteria: Investigators who provide a methodologically sound proposal to achieve the aims in the approved proposal.

Locations

US (1)