Trial Outcomes & Findings for Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant (NCT NCT02945150)

Last Updated: 2020-06-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

8 participants

Primary outcome timeframe

12 weeks post-treatment (24 weeks post-transplant)

Results posted on

2020-06-09

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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).
Overall Study STARTED	8
Overall Study SVR12	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients n=8 Participants 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).
Age, Continuous	55.9 years STANDARD_DEVIATION 9.4 • n=93 Participants
Sex: Female, Male Female	2 Participants n=93 Participants
Sex: Female, Male Male	6 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	8 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
End stage renal disease (ESRD) cause Diabetes/hypertension	3 Participants n=93 Participants
End stage renal disease (ESRD) cause IgA nephropathy	3 Participants n=93 Participants
End stage renal disease (ESRD) cause Polycystic kidney disease	1 Participants n=93 Participants
End stage renal disease (ESRD) cause Systemic lupus erythematosus	1 Participants n=93 Participants
Blood type A	5 Participants n=93 Participants
Blood type O	3 Participants n=93 Participants
Prior transplant	1 Participants n=93 Participants
BMI	29.9 kg/m^2 n=93 Participants
History of diabetes	4 Participants n=93 Participants
Days on waitlist prior to consent	482.5 days n=93 Participants
Days from consent to transplant	207.5 days n=93 Participants
Length of hospital stay 4 days	2 Participants n=93 Participants
Length of hospital stay 5 days	3 Participants n=93 Participants
Length of hospital stay 6 days	3 Participants n=93 Participants

PRIMARY outcome

Timeframe: 12 weeks post-treatment (24 weeks post-transplant)

Outcome measures

Outcome measures
Measure	Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients n=8 Participants 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).
Number of Participants With Undetectable HCV RNA at SVR12	8 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients n=8 Participants 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).
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 7	7 participants
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 14	8 participants
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 28	8 participants
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 56	8 participants
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 84	8 participants
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 112	8 participants
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 168	8 participants
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 252	8 participants
Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 Day 365	8 participants

Adverse Events

Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients n=8 participants at risk 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).
Surgical and medical procedures Lymphocele	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Renal and urinary disorders Renal vein thrombosis	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Renal and urinary disorders Delayed graft function	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Renal and urinary disorders Acute kidney injury (AKI)	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.

Other adverse events

Other adverse events
Measure	Elbasvir/Grazoprevir for HCV+ Kidney Transplant Recipients n=8 participants at risk 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).
Hepatobiliary disorders Elevated alanine transaminase (ALT)	37.5% 3/8 • Number of events 8 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Hepatobiliary disorders Elevated aspartate transaminase (AST)	37.5% 3/8 • Number of events 8 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Hepatobiliary disorders Elevated total bilirubin	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Gastrointestinal disorders Diarrhea	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Surgical and medical procedures Hematoma at surgical site	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Blood and lymphatic system disorders Hypophosphatemia	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.
Blood and lymphatic system disorders Hypomagnesemia	12.5% 1/8 • Number of events 1 • Adverse event data were collected from time of consent to 1 year post-transplant Adverse event data collection is still ongoing for two participants who have yet to reach the one year-post transplant mark.

Additional Information

Dr. Raymond Chung

Massachusetts General Hospital

Phone: 617-724-7562

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place