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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C; End Stage Renal Disease
• Intervention / Treatment: Drug: 300mg glecaprevir/pibrentasivir 120mg

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 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Deceased donor HCV RNA PCR+; 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; 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant; Other Names: Mavyret

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2018
• Primary Completion (Actual): December 19, 2019
• Study Completion (Actual): September 20, 2021

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 13, 2018

Study Record Updates

• Last Update Posted (Actual): October 19, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Kidney Diseases; Urologic Diseases; Liver Diseases; Renal Insufficiency; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Renal Insufficiency, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Kidney Failure, Chronic
• Other Study ID Numbers: IRB00174409

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Peer reviewed publications

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.: Yes