Pilot Study of Treatment for Subclinical AMR (Antibody-mediated Rejection) in Kidney Transplant Recipients

University of Colorado Denver (CU Denver)

Status and phase: Terminated; Early Phase 1

Conditions: Kidney Transplant Rejection

Treatments: Drug: Tacrolimus Extended Release Oral Tablet [Envarsus]; Other: Plasma Exchange and IVIG (Intravenous Immunoglobulin )

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03380936

17-1812

Details and patient eligibility

About

This is a pilot study to determine if extended release Envarsus at an optimal level is just as effective as more invasive standard therapies for subclinical (mild) AMR (antibody mediated rejection) in kidney transplant patients. Subjects will be randomized to either conversion to Envarsus XR (extended release); or, to a standard of care regimen of plasma exchange/IVIG (intravenous immunoglobulin)/rituximab treatments.

Full description

There is currently minimal data to guide treatment of mild graft damage in kidney transplant patients. Some of the current therapies used often come with dangerous complications (infections, malignancies, etc.). This is a pilot study to determine if extended release Envarsus at an optimal level is just as effective as more invasive standard therapies for subclinical (mild) AMR (antibody mediated rejection) in kidney transplant patients. The subjects will be randomized to either conversion from their current tacrolimus regimen to Envarsus XR (a once a day, extended release version of tacrolimus); or, to a regimen of 5 plasma exchanges/IVIG (intravenous immunoglobulin) treatments and one treatment with rituximab. Subjects who are within their first year of transplant will visit their doctor monthly for regular tests and checks and then will have a kidney biopsy at 6 months. Subjects who had their transplant over a year prior will see the doctor for tests and checks at 1, 3 and 5 months and then will have a biopsy of the kidney at month 6.

Enrollment: 4 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult (18+ years) recipients of kidney or kidney/pancreas transplants
• Willing to sign an IRB (institutional review board)-approved consent and to comply with study requirements
• DSA (donor specific antibodies) detected by SAB (single antigen beads) screening with MFI ≥ 2000
• Graft biopsy performed within prior 30 days
• Stable renal function defined by serum creatinine increase ≤ 30% over prior 6 months
• Subacute antibody-mediated rejection on biopsy defined by ptc + g + C4d ≥ 2 by Banff 2013 criteria

Exclusion criteria

• Kidney/liver or kidney/heart recipient
• Unwilling/unable to undergo screening biopsy
• HIV (human immunodeficiency virus), HCV (hepatitis-C virus), or HBsAg (hepatitis-B surface antigen) positive
• Active/untreated infection
• Acute cellular rejection with Banff grade 1b, 2a, 2b on initial biopsy requiring rATG (rabbit anti-thymocyte globulin) therapy
• Pregnant or nursing females

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4 participants in 2 patient groups

Arm 1 - conversion to Envarsus XR

Active Comparator group

Description:

Optimize: conversion to Envarsus XR (Tacrolimus Extended Release Oral Tablet \[Envarsus\]) with goal trough tac level \> 8 ng/ml, MPA at 720 mg bid unless medically contraindicated, prednisone at current dose (5mg) or continue taper to 5mg per center standard of care protocol

Treatment:

Drug: Tacrolimus Extended Release Oral Tablet [Envarsus]

Arm 2 - plasma exchange and IVIG

Active Comparator group

Description:

Treat clinical AMR: Plasma exchange x 5 treatments, each followed by IVIG 200 mg/kg except last dose of 1 gm/kg. Rituximab 375 mg/m2 following final plasma exchange treatment.

Treatment:

Other: Plasma Exchange and IVIG (Intravenous Immunoglobulin )