Renal Transplants in Hepatitis C Negative Recipients With Nucleic Acid Positive Donors

Study Overview
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Brief Summary
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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 4 weeks post-renal transplant.

Detailed Description
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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 4 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 4 weeks of G-P as prophylaxis for HCV D+/R- kidney transplant.

Official Title
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An Open-label Pilot Study to Determine the Safety and Efficacy of Fixed-dose Glecaprevir and Pibrentasvir Treatment in Hepatitis C Uninfected Recipients of Renal Transplants From Hepatitis C Infected Deceased Donors

Conditions
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End Stage Renal Disease, Hepatitis C

Intervention / Treatment
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* Drug: 300mg glecaprevir/pibrentasivir 120mg


Participation Criteria
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Eligibility Criteria
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Recipient Inclusion Criteria Participants ≥ 40 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 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 antigen antibody (cPRA) below 80% Recipient Exclusion Criteria Plan to receive a multi-organ transplant Plan to receive a dual kidney transplant (including en bloc) Prior solid organ 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
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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 300 mg glecaprevir/pibrentasivir 120 mg once daily by mouth for 4 weeks | Drug: 300mg glecaprevir/pibrentasivir 120mg<br>* 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant<br>* Other names: Mavyret;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral Response at Week 12 | This is the number of participants with undetectable hepatitis C RNA in the blood at 12 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 12 | 12 weeks after completing therapy | 
| Number of Participants With Grade 3 or Higher Treatment-related Adverse Events Related to the Use of G-P | Proportion of participants with grade 3 or higher treatment-related adverse events (AE) as assessed by US Department of Health and Human Services Common Terminology of AEs version 4. An AE is an unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5. Grade 3 Severe or medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. The investigator will determine if the AE is related to the treatment. | 4 weeks after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral Response at 1 Week | This is the number of participants with undetectable hepatitis C RNA in the blood at 1 week after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 1 | 1 week after completing therapy | 
| Viral Response at 2 Weeks | This is the number of participants with undetectable hepatitis C RNA in the blood at 2 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 2 | 2 weeks after completing therapy | 
| Viral Response at 4 Weeks | This is the number of participants with undetectable hepatitis C RNA in the blood at 4 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 4 | 4 weeks after completing therapy | 
| Viral Response at 8 Weeks | This is the number of participants with undetectable hepatitis C RNA in the blood at 8 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 8 | 8 weeks after completing therapy | 
| Antibody Development | Number of kidney transplant recipients that become reactive for HCV antibody | week 12 after discontinuation of therapy | 
| T-cell Response at Baseline | Measurement of t-cell response to HCV peptides, a marker of acute hepatitis C infection. This categorizes participants into no T-cell response, T-cell response to 1 peptide, T-cell response to 2 peptides and T-cell response to 3 peptides. | Baseline prior to induction therapy | 
| T-cell Response at 12 Weeks | Measurement of t-cell response to HCV peptides, a marker of acute hepatitis C infection. This categorizes participants into no T-cell response, T-cell response to 1 peptide, T-cell response to 2 peptides and T-cell response to 3 peptides. | Week12 after discontinuation of therapy | 
| Kidney Function at 6 Months | Serum creatinine mg/dL at 6 months following transplantation | 6 months following transplant | 
| Kidney Function at 12 Months | Serum creatinine mg/dL at 12 months following transplantation | 12 months following transplant |