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

Phase 4

Completed

Conditions: Hepatitis C
End-Stage Renal Disease

Interventions: Drug: Zepatier
Drug: Sofosbuvir
Drug: Ribavirin

Registration Number: NCT02781649

Lead Sponsor: Johns Hopkins University

Brief 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Donor genotype 2 or 3	Zepatier	Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks
Donor genotype 2 or 3	Sofosbuvir	Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks
Donor genotype 1a no resistance or 1b	Zepatier	Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks
Donor genotype 1a with resistance	Zepatier	Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks
Donor genotype 1a with resistance	Ribavirin	Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants With Grade 3 or Higher Treatment-related Adverse Events as US Department of Health and Human Services Common Terminology of Adverse Events (CTCAE) Version 4	12 weeks after transplant	Proportion of participants with grade 3 or higher treatment-related adverse events (AE) as assessed by US Department of Health and Human Services Common Terminology of AEs version 4. An AE is an unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5. Grade 3 Severe or medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. The investigator will determine if the AE is related to the treatment.

Secondary Outcome Measures

Name	Time	Method
Viral Response	12 weeks after completing treatment	This is the number of participants with undetectable hepatitis C RNA in the blood at 12 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA \< Lower Limit Of Quantification (LLOQ) at week 12
Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Mutations in the HCV Population From the Deceased Donors	Baseline	Number of participants with NS5A resistance mutations in the HCV population from the deceased donors. Number of donors with NS5A resistance mutations
IP-10 Elevations	12 weeks	Measurement of interferon (IFN)-gamma inducible protein 10 (IP-10) a marker of acute hepatitis C infection.
Kidney Function at 12 Months	12 months following transplantation	Serum creatinine mg/dL at 12 months following transplantation
Antibody Development	12 weeks	Number of kidney transplant recipients who become reactive for HCV antibody
Kidney Function at 6 Months	6 months following transplantation	Serum creatinine mg/dL at 6 months following transplantation