Kidney Transplants in Hepatitis C Negative Recipients With Hepatitis C Viremic Donors

Study Overview
=================
Brief Summary
-----------------
In this study, individuals without hepatitis C infection who are on the kidney transplant waitlist will receive a kidney from a deceased donor with hepatitis C infection and will be treated for hepatitis C at the same time. Treatment will include glecaprevir 300 mg / pibrentasvir 120 mg (G-P) administered on-call to the operating room for the renal transplant procedure and continued for 2 weeks post-renal transplant.

Detailed Description
-----------------
In this study, individuals without hepatitis C infection who are on the kidney transplant waitlist will receive a kidney from a deceased donor with hepatitis C infection and will be treated for hepatitis C at the same time. Treatment will include glecaprevir 300 mg / pibrentasvir 120 mg (G-P) administered on-call to the operating room for the renal transplant procedure and continued for 2 weeks post-renal transplant. The participant will continue to be tested for Hepatitis C for 12 weeks post-treatment. The primary hypothesis is that prophylactic treatment with glecaprevir/pibrentasvir before and after transplant will prevent the establishment of HCV infection in the recipients of kidneys from HCV-infected deceased donors. Based on the success of preliminary studies, the objective of the study is to evaluate the safety and efficacy of 2 weeks of G-P as prophylaxis for HCV D+/R- kidney transplant.

Official Title
-----------------
An Open-label, Non-randomized Pilot Study to Determine the Safety and Efficacy of Two Weeks of Fixed-dose Glecaprevir and Pibrentasvir as Pre- and Post-exposure Prophylactic Therapy

Conditions
-----------------
End Stage Renal Disease, Hepatitis C

Intervention / Treatment
-----------------
* Drug: Glecaprevir/pibrentasvir


Participation Criteria
=================
Eligibility Criteria
-----------------
Recipient Inclusion Criteria: Participants ≥ 18 years old On the deceased donor kidney waitlist at Johns Hopkins Hospital Awaiting a first or second kidney transplant No available living kidney donors On hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate <15 ml/min for ≥ past 90 days HCV-uninfected (by both antibody and RNA PCR) and without any behavioral risk factors for contracting HCV other than being on hemodialysis Calculated panel reactive anti-human leukocyte antigens (anti-HLA) antibody (flow cPRA) below 80% Recipient Exclusion Criteria: Plan to receive a multi-organ transplant Plan to receive a dual kidney transplant (including en bloc) History of prior solid organ transplant other than first kidney transplant Participating in another study that involves an intervention or investigational product Plan to receive a blood type incompatible kidney History of human immunodeficiency (HIV), hepatitis C (HCV), or active hepatitis B (HBV) infection, defined as being on active antiviral treatment for HBV, detectable hepatitis B surface Ag or detectable hepatitis B DNA Unable to safely substitute or discontinue a medication that is contraindicated with the study medication Psychiatric or physical illness that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deceased donor HCV RNA PCR+<br>Participants who receive a kidney from HCV RNA PCR + deceased donor will receive glecaprevir/pibrentasvir 300 mg/120 mg once daily by mouth for 2 weeks | Drug: Glecaprevir/pibrentasvir<br>* Glecaprevir/pibrentasvir 300mg/120mg once daily by mouth for 2 weeks post-transplant.<br>* Other names: Mavyret;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral Response as assessed by number of participants with undetectable hepatitis C RNA | This is the number of participants with undetectable hepatitis C RNA in the blood at 12 weeks after stopping treatment (Number of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ)). | 12 weeks after completing therapy |