Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant

A Proof of Concept Study of Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant

Proof of concept, open-label single center study for the donation of HCV positive kidneys to HCV negative patients, with preemptive, interventional treatment to prevent HCV transmission upon transplantation.

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination)

Detailed Description

The study objective is to determine if the administration of grazoprevir and elbasvir (with or without ribavirin) for 12-16 weeks after kidney transplantation prevents the spread of HCV infection from a donor kidney with known HCV genotype 1 or 4 infection to a HCV negative recipient as evidenced by a negative HCV viral RNA at 12 weeks post treatment

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must meet Massachusetts General Hospital (MGH) transplant center criteria and already be listed for isolated kidney transplant
2. No available living kidney donor
3. Has ≤ 730 days (two years) of accrued transplant waiting time if blood type A and ≤ 1095 days of accrued transplant waiting time if blood type B or O.
4. On chronic hemodialysis or peritoneal dialysis or has a glomerular filtration rate <15mL/min/1.73m2 at the time of screening
5. Weight ≥ 50kg
6. Serum alanine transaminase (ALT) within normal limits

Exclusion Criteria:

1. AB blood type
2. Body mass index (BMI > 35
3. History of liver disease
4. Pregnant or nursing (lactating) women
5. Cardiomyopathy (LV ejection fraction < 50%)
6. Positive crossmatch or positive donor specific antibodies
7. Human immunodeficiency virus (HIV) positive
8. Hepatitis C virus (HCV) RNA positive
9. Hepatitis B virus (HBV) surface antigen positive
10. Any contraindication to kidney transplant per MGH center protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Elbasvir/grazoprevir for HCV+ kidney transplant recipients; Elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination) treatment for Hepatitis C virus (HCV)-naive recipients who receive a kidney transplant from a deceased, HCV-infected donor Subjects receive first dose on-call to operating room, and continue daily for 12 weeks. Treatment length is extended to 16 weeks and ribavirin (daily dose 1000 mg for those <75 kg and 1200 mg for those ≥75 kg) if subject receives a kidney from a donor who is infected with HCV containing resistance-associated variants (RAV).

Drug: elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination); Elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination) treatment for Hepatitis C virus (HCV)-naive recipients who receive a kidney transplant from a deceased, HCV-infected donor Subjects receive first dose on-call to operating room, and continue daily for 12 weeks. Treatment length is extended to 16 weeks and ribavirin (daily dose 1000 mg for those <75 kg and 1200 mg for those ≥75 kg) if subject receives a kidney from a donor who is infected with HCV containing resistance-associated variants (RAV).; Other Names: Zepatier

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Undetectable HCV RNA at SVR12	Sustained virologic response at 12-weeks post-treatment (SVR12), as defined by negative HCV viral load, after 12-16 weeks of elbasvir/grazoprevir treatment in patients who receive a kidney transplant from a deceased donor infected with HCV.	12 weeks post-treatment (24 weeks post-transplant)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365	Subjects had Hepatitis C viral load assessed at each study visit. Here we looked at the proportion of subjects with undetectable serum HCV RNA at study day 7, 14, 28, 56, 84, 112, 168, 252, 365.	1 year post transplant

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Raymond Chung, MD, Massachusetts General Hospital (Partners Healthcare)

Publications and helpful links

General Publications

• Kucirka LM, Singer AL, Ros RL, Montgomery RA, Dagher NN, Segev DL. Underutilization of hepatitis C-positive kidneys for hepatitis C-positive recipients. Am J Transplant. 2010 May;10(5):1238-46. doi: 10.1111/j.1600-6143.2010.03091.x. Epub 2010 Mar 26.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): August 20, 2019
• Study Completion (Actual): March 5, 2020

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: October 24, 2016
• First Posted (Estimate): October 26, 2016

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: May 19, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: peritoneal dialysis; renal failure; hemodialysis; kidney transplant
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Anti-Infective Agents; Antiviral Agents; Grazoprevir
• Other Study ID Numbers: 2016P002051; Merck MISP 54841 (Other Grant/Funding Number: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared with study sponsor and with the hopes of publication.
• IPD Sharing Time Frame: Protocol will be shared for up to 1 year after the final patient has dosed.
• IPD Sharing Access Criteria: Protocol will only be shared with Institutional Review Board (IRB) approved study staff and PI approved collaborators.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• 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