Hepatitis C, Renal Failure Chronic
Conditions
Keywords
hemodialysis, renal failure, kidney transplant
Brief summary
Open label multi center study for the donation of HCV positive kidneys to HCV negative recipients with interventional treatment to prevent HCV transmission upon transplantation.
Detailed description
The study objective is to determine if the administration of the direct acting antiviral glecaprevir/pibrentasvir for 8 weeks after kidney transplantation is both safe and effective at preventing the spread of HCV infection from donor kidney with known HCV infection (all genotypes) to an HCV negative recipient as evidenced by a negative HCV viral RNA at 12 weeks post treatment.
Interventions
DRUGglecaprevir/pibrentasvir treatment
combination treatment with glecaprevir and pibrentasvir fixed dose tablet.
Sponsors
AbbVie
University of Pennsylvania
Johns Hopkins University
University of Cincinnati
Weill Medical College of Cornell University
University of Michigan
Northwestern University
Raymond Chung
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Recipient Inclusion Criteria: * Estimated glomerular filtration rate(eGFR) \< 15 ml/min/1.73 m2 * Listed for an isolated kidney transplantation * Able to understand and adhere to the study visit schedule and all other protocol requirements, and must voluntarily sign and date an informed consent * No available medically acceptable, compatible living kidney donor * Subject must agree to use an effective method of birth control per protocol specifications Recipient
Exclusion criteria
* History of severe, life-threatening or other significant sensitivity to immunosuppressants utilized in kidney transplant * Female who is pregnant, breastfeeding, or is planning to become pregnant during the course of the study * History of HIV * HCV RNA positive * HBV surface Ag-positive or detectable HBV DNA * Primary focal segmental glomerulosclerosis (FSGS) or disease process with increased risk of causing early graft failure as assessed by the transplant nephrologist and/or investigator team * Presence of clinically significant liver disease * Transplant candidate requiring antibody desensitization protocol for transplantation * Most recent calculated panel reactive antibody (cPRA) \>80%. * Prior recipient of a non-renal solid organ transplant Donor Organ Inclusion Criteria * Deceased donor organ with kidney donor profile index (KDPI) ≤0.85 * HCV RNA-positive Donor Organ
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Undetectable HCV | 12 weeks post treatment | HCV RNA \< LLOQ 12 weeks after the last actual dose of G/P |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With On-treatment Virologic Failure | During 8 week treatment course | HCV RNA \> LLOQ during G/P treatment |
| Percentage of Subjects With Post-treatment Virologic Relapse | During 12 week post treatment follow-up | HCV RNA \> LLOQ after completion of G/P treatment and prior HCV RNA \< LLOQ while on treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1) 8 weeks of HCV treatment with combination tablet of glecaprevir and pibrentasvir
glecaprevir/pibrentasvir treatment: combination treatment with glecaprevir and pibrentasvir fixed dose tablet. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1) |
|---|---|
| Age, Continuous | 57 years |
| BMI | 29.5 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Kidney disease etiology Congenital/genetic | 2 Participants |
| Kidney disease etiology Diabetic nephropathy | 11 Participants |
| Kidney disease etiology Hypertension | 9 Participants |
| Kidney disease etiology IgA nephropathy | 3 Participants |
| Kidney disease etiology Other | 2 Participants |
| Kidney disease etiology Polycystic kidney disease | 3 Participants |
| On dialysis at baseline No | 3 Participants |
| On dialysis at baseline Yes | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 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 | 1 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 21 Participants |
| Time from consent to transplant | 6.29 Weeks |
| Time spent on waitlist at time of consent | 137 Weeks |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 30 |
| other Total, other adverse events | 27 / 30 |
| serious Total, serious adverse events | 20 / 30 |
Outcome results
Primary
Number of Participants With Undetectable HCV
HCV RNA \< LLOQ 12 weeks after the last actual dose of G/P
Time frame: 12 weeks post treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1) | Number of Participants With Undetectable HCV | 30 Participants |
Secondary
Percentage of Subjects With On-treatment Virologic Failure
HCV RNA \> LLOQ during G/P treatment
Time frame: During 8 week treatment course
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1) | Percentage of Subjects With On-treatment Virologic Failure | 12 Participants |
Secondary
Percentage of Subjects With Post-treatment Virologic Relapse
HCV RNA \> LLOQ after completion of G/P treatment and prior HCV RNA \< LLOQ while on treatment
Time frame: During 12 week post treatment follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1) | Percentage of Subjects With Post-treatment Virologic Relapse | 0 Participants |