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

• ClinicalTrials.gov Identifier: NCT03627299
• Recruitment Status: Completed
• First Posted: August 13, 2018
• Results First Posted: August 24, 2020
• Last Update Posted: October 19, 2021
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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 4 weeks post-renal transplant.

Condition or disease	Intervention/treatment	Phase
End Stage Renal Disease; Hepatitis C	Drug: 300mg glecaprevir/pibrentasivir 120mg	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 25, 2018
• Actual Primary Completion Date: December 19, 2019
• Actual Study Completion Date: September 20, 2021

Arms and Interventions

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 Name: Mavyret

Outcome Measures

Primary Outcome Measures :

1. Viral Response at Week 12 [ Time Frame: 12 weeks after completing therapy ]
   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
2. Number of Participants With Grade 3 or Higher Treatment-related Adverse Events Related to the Use of G-P [ Time Frame: 4 weeks after transplant ]
   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.

Secondary Outcome Measures :

1. Viral Response at 1 Week [ Time Frame: 1 week after completing therapy ]
   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
2. Viral Response at 2 Weeks [ Time Frame: 2 weeks after completing therapy ]
   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
3. Viral Response at 4 Weeks [ Time Frame: 4 weeks after completing therapy ]
   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. Viral Response at 8 Weeks [ Time Frame: 8 weeks after completing therapy ]
   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
5. Antibody Development [ Time Frame: week 12 after discontinuation of therapy ]
   Number of kidney transplant recipients that become reactive for HCV antibody
6. T-cell Response at Baseline [ Time Frame: Baseline prior to induction therapy ]
   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.
7. T-cell Response at 12 Weeks [ Time Frame: Week12 after discontinuation of therapy ]
   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.
8. Kidney Function at 6 Months [ Time Frame: 6 months following transplant ]
   Serum creatinine mg/dL at 6 months following transplantation
9. Kidney Function at 12 Months [ Time Frame: 12 months following transplant ]
   Serum creatinine mg/dL at 12 months following transplantation

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21205

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Christine Durand, MD; Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] November 16, 2018

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03627299
• Other Study ID Numbers: IRB00174409
• First Posted: August 13, 2018
• Results First Posted: August 24, 2020
• Last Update Posted: October 19, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Peer reviewed publications

• 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

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis; Kidney Failure, Chronic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency