Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-negative Recipients

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. Hepatitis C treatment will include Grazoprevir
(GZR) 100 mg/Elbasvir (EBR) 50 mg administered on-call to the operating room for the renal
transplant procedure and continued for 12 weeks post-renal transplant. The donor hepatitis C
genotype will be tested. If the donor has genotype 1a without resistance or genotype 1b
treatment will remain GZR/EBR for 12 weeks. If the donor has genotype 1a with resistance
variants, then Ribavirin will be added and treatment will be given for 16 weeks starting from
the date ribavirin was added. If the donor has hepatitis C genotype 2 or 3, Sofosbuvir will
be added and treatment will be for 12 weeks from the date Sofosbuvir was added.

Inclusion Criteria:

- Participants ≥ 50 years old

- On the deceased donor kidney waiting list at Johns Hopkins Hospital

- Awaiting a first kidney transplant

- No available living kidney donors

- On hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) 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 (HLA) antibody (cPRA) below 20
percent

- Female who is:

- practicing total abstinence from sexual intercourse (minimum 1 complete menstrual
cycle)

- sexually active with female partners only

- not of childbearing potential: defined as postmenopausal for at least 2 years
prior to screening defined as amenorrheic for longer than 2 years, age
appropriate, and confirmed by a follicle-stimulating hormone level indicating a
postmenopausal state, or surgically sterile: defined as bilateral tubal ligation,
bilateral oophorectomy or hysterectomy or has a vasectomized partner(s);

- of childbearing potential and sexually active with male partner(s): currently
using at least one effective method of birth control at the time of screening and
agree to practice two effective methods of birth control while receiving study
drug (as outlined in the participant information and consent form starting with
Study Day 1 and for 30 days after stopping study drug, or for 6 months after
stopping study drug if receiving RBV (Note: Estrogen-containing hormonal
contraceptives, including oral, injectable, implantable, patch and ring
varieties, may not be used during study drug treatment).

- Males who are not surgically sterile and are sexually active with female partner(s) of
childbearing potential must agree to practice two effective forms of birth control (as
outlined in the participant information and consent form) throughout the course of the
study, starting with starting with Study Day 1 and for 30 days after stopping study
drug, or for 6 months after stopping study drug if receiving ribavirin (RBV)

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

- Active or unresolved bacterial, viral, or fungal infection that is clinically
significant

- History of cirrhosis or pre-existing liver disease such as non-alcoholic
steatohepatitis

- History of illicit drug use or alcohol abuse within 12 months prior to screening

- 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.