End Stage Renal Disease, Hepatitis C
Conditions
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.
Interventions
DRUG300mg glecaprevir/pibrentasivir 120mg
300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant
Sponsors
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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. |
| 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 |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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
300mg glecaprevir/pibrentasivir 120mg: 300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Deceased Donor HCV RNA PCR+ |
|---|---|
| Age, Continuous | 67 years |
| Blood Type A or AB | 5 Participants |
| Blood Type B | 1 Participants |
| Blood Type O | 4 Participants |
| Primary Cause of Renal Failure Glomerulonephritis | 2 Participants |
| Primary Cause of Renal Failure Hypertension | 4 Participants |
| Primary Cause of Renal Failure Nephrolithiasis | 1 Participants |
| Primary Cause of Renal Failure Polycystic Kidney Disease | 2 Participants |
| Primary Cause of Renal Failure Reflux Nephropathy | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
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.
Time frame: 4 weeks after transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Number of Participants With Grade 3 or Higher Treatment-related Adverse Events Related to the Use of G-P | 0 Participants |
Primary
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
Time frame: 12 weeks after completing therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Viral Response at Week 12 | 10 Participants |
Secondary
Antibody Development
Number of kidney transplant recipients that become reactive for HCV antibody
Time frame: week 12 after discontinuation of therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Antibody Development | 9 Participants |
Secondary
Kidney Function at 12 Months
Serum creatinine mg/dL at 12 months following transplantation
Time frame: 12 months following transplant
Population: One participant did not have serum creatinine checked at 12 months post-transplantation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Kidney Function at 12 Months | 1.33 mg/dL |
Secondary
Kidney Function at 6 Months
Serum creatinine mg/dL at 6 months following transplantation
Time frame: 6 months following transplant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Kidney Function at 6 Months | 1.32 mg/dL |
Secondary
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.
Time frame: Week12 after discontinuation of therapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Deceased Donor HCV RNA PCR+ | T-cell Response at 12 Weeks | No T-cell response at 12 weeks | 5 Participants |
| Deceased Donor HCV RNA PCR+ | T-cell Response at 12 Weeks | T-cell response to 1 peptide at 12 weeks | 3 Participants |
| Deceased Donor HCV RNA PCR+ | T-cell Response at 12 Weeks | T-cell response to 2 peptides at 12 weeks | 1 Participants |
| Deceased Donor HCV RNA PCR+ | T-cell Response at 12 Weeks | T-cell response to 3 peptides at 12 weeks | 1 Participants |
Secondary
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.
Time frame: Baseline prior to induction therapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Deceased Donor HCV RNA PCR+ | T-cell Response at Baseline | No T-cell response at baseline | 6 Participants |
| Deceased Donor HCV RNA PCR+ | T-cell Response at Baseline | T-cell response to 1 peptide at baseline | 1 Participants |
| Deceased Donor HCV RNA PCR+ | T-cell Response at Baseline | T-cell response to 2 peptides at baseline | 2 Participants |
| Deceased Donor HCV RNA PCR+ | T-cell Response at Baseline | T-cell response to 3 peptides at baseline | 1 Participants |
Secondary
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
Time frame: 1 week after completing therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Viral Response at 1 Week | 8 Participants |
Secondary
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
Time frame: 2 weeks after completing therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Viral Response at 2 Weeks | 10 Participants |
Secondary
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
Time frame: 4 weeks after completing therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Viral Response at 4 Weeks | 10 Participants |
Secondary
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
Time frame: 8 weeks after completing therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Deceased Donor HCV RNA PCR+ | Viral Response at 8 Weeks | 10 Participants |