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

Primary Purpose

End Stage Renal Disease, Hepatitis C

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
300mg glecaprevir/pibrentasivir 120mg
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Renal Disease

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Johns Hopkins University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deceased donor HCV RNA PCR+

Arm Description

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

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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
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
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
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
Antibody Development
Number of kidney transplant recipients that become reactive for HCV antibody
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.
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.
Kidney Function at 6 Months
Serum creatinine mg/dL at 6 months following transplantation
Kidney Function at 12 Months
Serum creatinine mg/dL at 12 months following transplantation

Full Information

First Posted
August 8, 2018
Last Updated
September 21, 2021
Sponsor
Johns Hopkins University
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1. Study Identification

Unique Protocol Identification Number
NCT03627299
Brief Title
Renal Transplants in Hepatitis C Negative Recipients With Nucleic Acid Positive Donors
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
September 25, 2018 (Actual)
Primary Completion Date
December 19, 2019 (Actual)
Study Completion Date
September 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University

4. Oversight

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
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease, Hepatitis C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deceased donor HCV RNA PCR+
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
300mg glecaprevir/pibrentasivir 120mg
Other Intervention Name(s)
Mavyret
Intervention Description
300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
Primary Outcome Measure Information:
Title
Viral Response at Week 12
Description
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
Time Frame
12 weeks after completing therapy
Title
Number of Participants With Grade 3 or Higher Treatment-related Adverse Events Related to the Use of G-P
Description
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.
Time Frame
4 weeks after transplant
Secondary Outcome Measure Information:
Title
Viral Response at 1 Week
Description
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
Time Frame
1 week after completing therapy
Title
Viral Response at 2 Weeks
Description
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
Time Frame
2 weeks after completing therapy
Title
Viral Response at 4 Weeks
Description
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
Time Frame
4 weeks after completing therapy
Title
Viral Response at 8 Weeks
Description
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
Time Frame
8 weeks after completing therapy
Title
Antibody Development
Description
Number of kidney transplant recipients that become reactive for HCV antibody
Time Frame
week 12 after discontinuation of therapy
Title
T-cell Response at Baseline
Description
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.
Time Frame
Baseline prior to induction therapy
Title
T-cell Response at 12 Weeks
Description
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.
Time Frame
Week12 after discontinuation of therapy
Title
Kidney Function at 6 Months
Description
Serum creatinine mg/dL at 6 months following transplantation
Time Frame
6 months following transplant
Title
Kidney Function at 12 Months
Description
Serum creatinine mg/dL at 12 months following transplantation
Time Frame
12 months following transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christine Durand, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Peer reviewed publications

Learn more about this trial

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

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