Kidney Failure, Hepatitis C, Kidney Disease, Chronic
Conditions
Keywords
Kidney Transplant, Kidney Failure, HCV, Hepatitis C
Brief summary
This is a single center study characterizing the experience of administration of 4 weeks of pan-genotypic DAA therapy in kidney transplantation to prevent the transmission of hepatitis C virus infection from an HCV-positive donor kidney to an HCV-negative recipient.
Detailed description
The goal of this study is to determine if the administration of glecaprevir and pibrentasvir (G/P) for 4 weeks beginning in the immediate peri-transplant period prevents establishment of HCV infection in HCV negative recipients receiving transplanted kidneys from HCV RNA positive donors.
Interventions
4 weeks of treatment starting within 24 hrs of kidney transplant
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Recipient) 1. Met MGH Transplant Center criteria and already listed for kidney transplant with stage 5 CKD / ESRD (eGFR \<15 ml/min/1.73m2 or on renal replacement therapy) 2. Must agree to birth control. Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy and at least one barrier method 3. No evidence of clinically significant liver disease at the time of transplant readiness as determined by the clinical team 4. Able to sign informed consent Inclusion Criteria (Deceased Donor) 1. Detectable HCV NAT test 2. KDPI score is less than ≤ 0.850 3. Traditional Donor Selection Criteria Met - acceptable for transplantation per usual evaluation
Exclusion criteria
(Recipient) 1. Pregnant or nursing (lactating) women 2. HBV positivity (Ag or DNA) 3. Any contra-indication to kidney transplantation per MGH transplant center protocol 4. Any signs or symptoms of clinically significant chronic liver disease per transplant center physician 5. Inability to discontinue any medication with a known drug-drug interaction as listed in the G/P package insert
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Undetectable Blood HCV RNA Level | 12 weeks post last dose of treatment with G/P | Negative HCV RNA by blood testing at 12 weeks after the last dose of G/P |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 1 Year Study Period | Serious and non-serious adverse events attributed to study drug and/or HCV-viremia |
| HCV RNA Viral Load | Measured at Week 2 and Week 4 of Treatment; | Assessment of HCV RNA viral load at on-treatment visits, measured at both week 2 and week 4 on treatment. The viral loads measured at Week 2 and 4 are averaged together and reported in copies per mL |
| Allograft Function | 1 Year Study Period | Post-transplant allograft function measured by mean eGFR over study period |
| Rate of Death, Graft Failure, Acute Allograft Rejection, Delayed Graft Function, ALT Elevation | 1 Year Study Period | The rate of clinical safety outcomes: death, graft failure, acute allograft rejection, delayed graft functions, ALT elevations \> 5x ULN related to study treatment with glecaprevir/Pibrentasvir |
Countries
United States
Participant flow
Recruitment details
18 HCV negative subjects were agreed to receive kidney transplant from HCV RNA-positive donors, resulting in 2 subjects enrolled (transplanting with an HCV RNA positive kidney). Recruitment began in May 2021 and ended in August 2023 when enrollment was closed prior to study completion.
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Direct Acting Antiviral for HCV 4 week treatment period with glecaprevir and pibrentasvir (G/P) initiated within 24 hours of transplant
Glecaprevir and Pibrentasvir: 4 weeks of treatment starting within 24 hrs of kidney transplant | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Treatment With Direct Acting Antiviral for HCV |
|---|---|
| Adults receiving kidney transplant from HCV RNA positive donor | 2 Participants |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 1 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Number of Participants With Undetectable Blood HCV RNA Level
Negative HCV RNA by blood testing at 12 weeks after the last dose of G/P
Time frame: 12 weeks post last dose of treatment with G/P
Population: Subjects receiving at least 1 dose of G/P after receipt of donor HCV RNA positive kidney transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Direct Acting Antiviral for HCV | Number of Participants With Undetectable Blood HCV RNA Level | 2 Participants |
Secondary
Adverse Events
Serious and non-serious adverse events attributed to study drug and/or HCV-viremia
Time frame: 1 Year Study Period
Population: Subjects receiving HCV RNA positive kidney transplant and initiating treatment with DAA experience protocol related adverse events
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Direct Acting Antiviral for HCV | Adverse Events | 0 Participants |
Secondary
Allograft Function
Post-transplant allograft function measured by mean eGFR over study period
Time frame: 1 Year Study Period
Population: Data not collected
Secondary
HCV RNA Viral Load
Assessment of HCV RNA viral load at on-treatment visits, measured at both week 2 and week 4 on treatment. The viral loads measured at Week 2 and 4 are averaged together and reported in copies per mL
Time frame: Measured at Week 2 and Week 4 of Treatment;
Population: Subjects receiving HCV RNA positive kidney transplant and initiating treatment with DAA with a negative HCV viral load at the 2 week and 4 week treatment mark of the full 4 week treatment period. For both participants, the measured HCV RNA was 0 copies/mL (no copies present in the sample/undetectable HCV RNA).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment With Direct Acting Antiviral for HCV | HCV RNA Viral Load | 0 copies per mL |
Secondary
Rate of Death, Graft Failure, Acute Allograft Rejection, Delayed Graft Function, ALT Elevation
The rate of clinical safety outcomes: death, graft failure, acute allograft rejection, delayed graft functions, ALT elevations \> 5x ULN related to study treatment with glecaprevir/Pibrentasvir
Time frame: 1 Year Study Period
Population: Reportable outcome events in patients who 4 weeks of study treatment with glecaprevir/pibrentasvir
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment With Direct Acting Antiviral for HCV | Rate of Death, Graft Failure, Acute Allograft Rejection, Delayed Graft Function, ALT Elevation | 0 reported outcome events |