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

Phase 4

Completed

• Conditions: Renal Failure
• Interventions: Drug: elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination)

• Registration Number: NCT02945150
• Lead Sponsor: Massachusetts General Hospital

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

Study Timeline

• Study First Submitted: 2016-10-21
• Study First Submitted QC: 2016-10-24
• Study First Posted: 2016-10-26
• Study Start: 2017-02-01
• Primary Completion: 2019-08-20
• Results First Submitted: 2020-01-10
• Results First Submitted QC: 2020-02-12
• Results First Posted: 2020-02-26
• Study Completion: 2020-03-05
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-19
• Last Update Posted: 2020-06-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Elbasvir/grazoprevir for HCV+ kidney transplant recipients	elbasvir (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).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States