Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-negative Recipients
Condition: End-Stage Renal Disease; Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Kidney Failure, Chronic
Intervention: Zepatier; Ribavirin; Sofosbuvir
Intervention description: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks; Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses; Sofosbuvir 400 mg daily
Intervention MeSH terms: Ribavirin; Sofosbuvir; Grazoprevir; Elbasvir-grazoprevir drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Renal; Transplants; Hepatitis C; HCV-negative; Infected; Donors

Summary:

      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. 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.
    

Eligibility criteria:

        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.