Renal Failure
Conditions
Keywords
hemodialysis, peritoneal dialysis, renal failure, kidney transplant
Brief summary
Proof of concept, open-label single center study for the donation of HCV positive kidneys to HCV negative patients, with preemptive, interventional treatment to prevent HCV transmission upon transplantation.
Detailed description
The study objective is to determine if the administration of grazoprevir and elbasvir (with or without ribavirin) for 12-16 weeks after kidney transplantation prevents the spread of HCV infection from a donor kidney with known HCV genotype 1 or 4 infection to a HCV negative recipient as evidenced by a negative HCV viral RNA at 12 weeks post treatment
Interventions
DRUGelbasvir (50mg) / grazoprevir (100mg) (fixed dose combination)
Elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination) treatment for Hepatitis C virus (HCV)-naive recipients who receive a kidney transplant from a deceased, HCV-infected donor Subjects receive first dose on-call to operating room, and continue daily for 12 weeks. Treatment length is extended to 16 weeks and ribavirin (daily dose 1000 mg for those \<75 kg and 1200 mg for those ≥75 kg) if subject receives a kidney from a donor who is infected with HCV containing resistance-associated variants (RAV).
Sponsors
Merck Sharp & Dohme LLC
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Must meet Massachusetts General Hospital (MGH) transplant center criteria and already be listed for isolated kidney transplant 2. No available living kidney donor 3. Has ≤ 730 days (two years) of accrued transplant waiting time if blood type A and ≤ 1095 days of accrued transplant waiting time if blood type B or O. 4. On chronic hemodialysis or peritoneal dialysis or has a glomerular filtration rate \<15mL/min/1.73m2 at the time of screening 5. Weight ≥ 50kg 6. Serum alanine transaminase (ALT) within normal limits
Exclusion criteria
1. AB blood type 2. Body mass index (BMI \> 35 3. History of liver disease 4. Pregnant or nursing (lactating) women 5. Cardiomyopathy (LV ejection fraction \< 50%) 6. Positive crossmatch or positive donor specific antibodies 7. Human immunodeficiency virus (HIV) positive 8. Hepatitis C virus (HCV) RNA positive 9. Hepatitis B virus (HBV) surface antigen positive 10. Any contraindication to kidney transplant per MGH center protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Undetectable HCV RNA at SVR12 | 12 weeks post-treatment (24 weeks post-transplant) | Sustained virologic response at 12-weeks post-treatment (SVR12), as defined by negative HCV viral load, after 12-16 weeks of elbasvir/grazoprevir treatment in patients who receive a kidney transplant from a deceased donor infected with HCV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | 1 year post transplant | Subjects had Hepatitis C viral load assessed at each study visit. Here we looked at the proportion of subjects with undetectable serum HCV RNA at study day 7, 14, 28, 56, 84, 112, 168, 252, 365. |
Countries
United States
Participant flow
Pre-assignment details
33 patients signed consent for the study. Of those, 23 patients were deemed ready for transplant and were put on the waitlist for a HCV kidney (10 patients did not meet the readiness criteria for kidney transplantation). Of those, 8 patients were transplanted with an HCV+ kidney.
Participants by arm
| Arm | Count |
|---|---|
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients Elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination) treatment for Hepatitis C virus (HCV)-naive recipients who receive a kidney transplant from a deceased, HCV-infected donor
Subjects receive first dose on-call to operating room, and continue daily for 12 weeks. Treatment length is extended to 16 weeks and ribavirin (daily dose 1000 mg for those \<75 kg and 1200 mg for those ≥75 kg) if subject receives a kidney from a donor who is infected with HCV containing resistance-associated variants (RAV). | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients |
|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 9.4 |
| Blood type A | 5 Participants |
| Blood type O | 3 Participants |
| BMI | 29.9 kg/m^2 |
| Days from consent to transplant | 207.5 days |
| Days on waitlist prior to consent | 482.5 days |
| End stage renal disease (ESRD) cause Diabetes/hypertension | 3 Participants |
| End stage renal disease (ESRD) cause IgA nephropathy | 3 Participants |
| End stage renal disease (ESRD) cause Polycystic kidney disease | 1 Participants |
| End stage renal disease (ESRD) cause Systemic lupus erythematosus | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| History of diabetes | 4 Participants |
| Length of hospital stay 4 days | 2 Participants |
| Length of hospital stay 5 days | 3 Participants |
| Length of hospital stay 6 days | 3 Participants |
| Prior transplant | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 8 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 4 / 8 |
| serious Total, serious adverse events | 4 / 8 |
Outcome results
Primary
Number of Participants With Undetectable HCV RNA at SVR12
Sustained virologic response at 12-weeks post-treatment (SVR12), as defined by negative HCV viral load, after 12-16 weeks of elbasvir/grazoprevir treatment in patients who receive a kidney transplant from a deceased donor infected with HCV.
Time frame: 12 weeks post-treatment (24 weeks post-transplant)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Participants With Undetectable HCV RNA at SVR12 | 8 Participants |
Secondary
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365
Subjects had Hepatitis C viral load assessed at each study visit. Here we looked at the proportion of subjects with undetectable serum HCV RNA at study day 7, 14, 28, 56, 84, 112, 168, 252, 365.
Time frame: 1 year post transplant
Population: Patients who received a HCV+ kidney transplant and were treated with elbasvir (50mg) / grazoprevir (100mg) for 12 weeks following transplant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 7 | 7 participants |
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 14 | 8 participants |
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 28 | 8 participants |
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 56 | 8 participants |
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 84 | 8 participants |
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 112 | 8 participants |
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 168 | 8 participants |
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 252 | 8 participants |
| Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients | Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Day 365 | 8 participants |