Renal Transplants in Hepatitis C Negative Recipients With Nucleic Acid Positive Donors
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 |
---|---|---|
|
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
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
- 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
- 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
- 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
- Antibody Development [week 12 after discontinuation of therapy]
Number of kidney transplant recipients that become reactive for HCV antibody
- 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.
- 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.
- Kidney Function at 6 Months [6 months following transplant]
Serum creatinine mg/dL at 6 months following transplantation
- Kidney Function at 12 Months [12 months following transplant]
Serum creatinine mg/dL at 12 months following transplantation
Eligibility Criteria
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
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.- IRB00174409
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
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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
|
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
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 |
ChristineDurand@jhmi.edu |
- IRB00174409