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

Sponsor
Johns Hopkins University (Other)
Overall Status
Completed
CT.gov ID
NCT03627299
Collaborator
(none)
11
1
1
35.8
0.3

Study Details

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
  • 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
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 :
Sep 25, 2018
Actual Primary Completion Date :
Dec 19, 2019
Actual Study Completion Date :
Sep 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 Names:
  • Mavyret
  • Outcome Measures

    Primary Outcome Measures

    1. Viral Response at Week 12 [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 [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 [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 [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 [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 [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 [week 12 after discontinuation of therapy]

      Number of kidney transplant recipients that become reactive for HCV antibody

    6. T-cell Response at Baseline [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 [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 [6 months following transplant]

      Serum creatinine mg/dL at 6 months following transplantation

    9. Kidney Function at 12 Months [12 months following transplant]

      Serum creatinine mg/dL at 12 months following transplantation

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Site City State Country Postal Code
    1 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)

    More Information

    Publications

    None provided.
    Responsible Party:
    Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT03627299
    Other Study ID Numbers:
    • IRB00174409
    First Posted:
    Aug 13, 2018
    Last Update Posted:
    Oct 19, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    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:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Of 11 participants who signed consent, 10 received organ offers from HCV+ deceased donors. The remaining participant did not receive an offer before enrollment in the study closed.
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Period Title: Overall Study
    STARTED 10
    COMPLETED 10
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Overall Participants 10
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    67
    Sex: Female, Male (Count of Participants)
    Female
    3
    30%
    Male
    7
    70%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    10%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    2
    20%
    White
    7
    70%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Primary Cause of Renal Failure (Count of Participants)
    Hypertension
    4
    40%
    Polycystic Kidney Disease
    2
    20%
    Glomerulonephritis
    2
    20%
    Nephrolithiasis
    1
    10%
    Reflux Nephropathy
    1
    10%
    Blood Type (Count of Participants)
    O
    4
    40%
    A or AB
    5
    50%
    B
    1
    10%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    Count of Participants [Participants]
    10
    100%
    2. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    Count of Participants [Participants]
    0
    0%
    3. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    Count of Participants [Participants]
    8
    80%
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    Count of Participants [Participants]
    10
    100%
    5. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    Count of Participants [Participants]
    10
    100%
    6. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    Count of Participants [Participants]
    10
    100%
    7. Secondary Outcome
    Title Antibody Development
    Description Number of kidney transplant recipients that become reactive for HCV antibody
    Time Frame week 12 after discontinuation of therapy

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    Count of Participants [Participants]
    9
    90%
    8. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    No T-cell response at baseline
    6
    60%
    T-cell response to 1 peptide at baseline
    1
    10%
    T-cell response to 2 peptides at baseline
    2
    20%
    T-cell response to 3 peptides at baseline
    1
    10%
    9. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    No T-cell response at 12 weeks
    5
    50%
    T-cell response to 1 peptide at 12 weeks
    3
    30%
    T-cell response to 2 peptides at 12 weeks
    1
    10%
    T-cell response to 3 peptides at 12 weeks
    1
    10%
    10. Secondary Outcome
    Title Kidney Function at 6 Months
    Description Serum creatinine mg/dL at 6 months following transplantation
    Time Frame 6 months following transplant

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 10
    Median (Full Range) [mg/dL]
    1.32
    11. Secondary Outcome
    Title Kidney Function at 12 Months
    Description Serum creatinine mg/dL at 12 months following transplantation
    Time Frame 12 months following transplant

    Outcome Measure Data

    Analysis Population Description
    One participant did not have serum creatinine checked at 12 months post-transplantation.
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    Measure Participants 9
    Median (Full Range) [mg/dL]
    1.33

    Adverse Events

    Time Frame Adverse events were collected for 12 months from initiation of treatment
    Adverse Event Reporting Description
    Arm/Group Title Deceased Donor HCV RNA PCR+
    Arm/Group 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 300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
    All Cause Mortality
    Deceased Donor HCV RNA PCR+
    Affected / at Risk (%) # Events
    Total 0/10 (0%)
    Serious Adverse Events
    Deceased Donor HCV RNA PCR+
    Affected / at Risk (%) # Events
    Total 3/10 (30%)
    Infections and infestations
    Urosepsis 1/10 (10%) 1
    Urinary Tract Infection 1/10 (10%) 2
    Renal and urinary disorders
    Renal Vein Thrombosis 1/10 (10%) 1
    Acute Kidney Injury 1/10 (10%) 1
    Hematuria 1/10 (10%) 1
    Perinephric Fluid Collection 1/10 (10%) 1
    Other (Not Including Serious) Adverse Events
    Deceased Donor HCV RNA PCR+
    Affected / at Risk (%) # Events
    Total 0/10 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Christine Durand, MD
    Organization Johns Hopkins University
    Phone 410-955-5684
    Email ChristineDurand@jhmi.edu
    Responsible Party:
    Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT03627299
    Other Study ID Numbers:
    • IRB00174409
    First Posted:
    Aug 13, 2018
    Last Update Posted:
    Oct 19, 2021
    Last Verified:
    Sep 1, 2021