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

Renal Failure Clinical Trial

Official title:

A Proof of Concept Study of Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02945150
• Other study ID #: 2016P002051
• Secondary ID: Merck MISP 54841
• Status: Completed
• Phase: Phase 4
• Start date: February 1, 2017
• Est. completion date: March 5, 2020

Study information

• Verified date: May 2020
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 5, 2020
• Est. primary completion date: August 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Failure
• Renal Insufficiency

Intervention

Drug:
• 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).

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kucirka LM, Singer AL, Ros RL, Montgomery RA, Dagher NN, Segev DL. Underutilization of hepatitis C-positive kidneys for hepatitis C-positive recipients. Am J Transplant. 2010 May;10(5):1238-46. doi: 10.1111/j.1600-6143.2010.03091.x. Epub 2010 Mar 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Undetectable HCV RNA at SVR12	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.	12 weeks post-treatment (24 weeks post-transplant)
Secondary	Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365	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.	1 year post transplant