Single Patient Protocol for Donor HCV-positive to Recipient HCV-negative Kidney Transplant in a Patient at Risk for Loss of Dialysis Access

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04614142

Collaborator

(none)

Enrollment

Location

Arm

8.7

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a single patient, single center study evaluating if administration of pan-genotypic DAA therapy on day 3 (+/- 2 days) post-kidney transplant prevents the transmission of hepatitis C virus infection from an HCV-positive donor kidney to an HCV-negative recipient.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease Chronic Hepatitis c	Drug: Glecaprevir / Pibrentasvir Oral Tablet [Mavyret]	Phase 4

Detailed Description

The patient selected for this study previously received a kidney transplant under protocol 2016P002051. Unfortunately, she experienced primary graft nonfunction due to a renal vein thrombus and acute thrombotic microangiopathy and the transplanted HCV+ kidney was removed. She continued glecaprevir and pibrentasvir for the full course (8 weeks of treatment) and was cured of HCV. However, she continues on dialysis requiring ongoing, albeit low dose, immunosuppression after her failed transplant. This causes increased risk of infection and other dialysis-related morbidity. Futhermore, she is at risk of access loss due to multiple failed fistula attempts and prior dialysis catheter line thrombosis. Of note, she also failed a trial of peritoneal dialysis due to development of a large pleural effusion (a known treatment-limiting complication of peritoneal dialysis). Thus, this young patient, is at risk of losing dialysis access which could lead to death. The MGH transplant team has now decided that she could be retransplanted with alterations in peri-transplant anticoagulation and immunosuppression (eculizumab) that they are confident should decrease her risk of peri-transplant thrombosis and recurrent TMA. Thus, we desire to expedite her access to re-transplant. Through this protocol, this recipient will be given the opportunity to accept a kidney that is HCV antibody positive and nucleic acid test (NAT) negative or HCV NAT positive and will be treated with oral glecaprevir (300mg)/pibrentasvir (120mg) (G/P, MavyretTM) on day 3 (+/- 2 days) post-kidney transplant to prevent the transmission of HCV infection at the time of transplant. Our goal is to provide access to kidney transplantation as soon as possible, with a donor of any genotype of infection, with elimination of the potential HCV infection by therapy used on day 3 (+/- 2 days) in the case of HCV NAT+ transplant and surveillance and reactive therapy in the case of HCV antibody positive NAT- transplant.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Single Patient Protocol for Donor HCV-positive to Recipient HCV-negative Kidney Transplant in a Patient at Risk for Loss of Dialysis Access

Actual Study Start Date :

Nov 13, 2020

Actual Primary Completion Date :

Aug 4, 2021

Actual Study Completion Date :

Aug 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: Glecaprevir/pibrentasvir for HCV+ kidney transplant recipient Glecaprevir (100mg) / pibrentasvir (40mg) (fixed dose combination) treatment for Hepatitis C virus (HCV)-naive recipients who receive a kidney transplant from a deceased, HCV-infected donor. Subject will receive first dose on day 3 (+/- 2 days) post-kideny transplantation and continue daily for 8 weeks.	Drug: Glecaprevir / Pibrentasvir Oral Tablet [Mavyret] The subject will begin an 8 week course of therapy with glecaprevir (100mg) / pibrentasvir (40mg) starting on day 3 (+/- 2 days) post-kidney transplantation from a hepatitis C positive donor.

Arm

Intervention/Treatment

Experimental: Experimental: Glecaprevir/pibrentasvir for HCV+ kidney transplant recipient

Glecaprevir (100mg) / pibrentasvir (40mg) (fixed dose combination) treatment for Hepatitis C virus (HCV)-naive recipients who receive a kidney transplant from a deceased, HCV-infected donor. Subject will receive first dose on day 3 (+/- 2 days) post-kideny transplantation and continue daily for 8 weeks.

Drug: Glecaprevir / Pibrentasvir Oral Tablet [Mavyret]

The subject will begin an 8 week course of therapy with glecaprevir (100mg) / pibrentasvir (40mg) starting on day 3 (+/- 2 days) post-kidney transplantation from a hepatitis C positive donor.

Outcome Measures

Primary Outcome Measures

Hepatitis C viral load (RNA) [20 weeks post-transplant (12-weeks post-treatment)]
Negative hepatitis C viral load (RNA) tested using PCR at 12 weeks post-treatment (SVR12)

Eligibility Criteria

Criteria

Ages Eligible for Study:

34 Years to 44 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Donor Inclusion Criteria:

Detectable HCV Antibody Positivity
KDPI score is less than ≤ 0.650
Traditional Donor Selection Criteria Met - acceptable for transplantation per usual evaluation at MGH

Donor exclusion criteria

Donor has been known to have previously received and failed HCV treatment with a direct-acting antiviral agent
Confirmed HIV
Confirmed HBV positive (surface antigen or HBV DNA positive)
Kidney anatomical damage or significant pathology noted during recovery
Significant liver disease or signs of liver decompensation (splenomegaly, ascites) noted during recovery (advanced fibrosis or cirrhosis)
Any standard contra-indication to donation noted in donor (significant malignancy, unusual infection)

Recipient Inclusion/Exclusion Criteria

Previously enrolled in IRB 2016P002051 and experienced primary graft nonfunction due to renal vein thrombosis and acute thrombotic microangiopathy
Willing and able to sign informed consent