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

NCT ID: NCT03380936

Last Updated: 2020-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

EARLY_PHASE1

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-17

Study Completion Date

2019-10-16

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Kidney Transplant Rejection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Only patients meeting histologic criteria for AMR by Banff 2013 criteria will be randomized (ptc + g + c4d ≥ 2). Subjects will be randomized to either undergo optimization (conversion to Envarsus with goal trough tacrolimus level \> 8 ng/ml, mycophenolic acid at 720 mg, prednisone at current dose (5mg) or continue taper to 5mg per center standard of care protocol of or treatment.); or, to treat clinical AMR (antibody mediated rejection) with plasma exchange x 5 treatments, each followed by IVIG (intravenous immunoglobulin) 200 mg/kg except last dose of 1 gm/kg. Rituximab 375 mg/m2 following final plasma exchange treatment.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1 - conversion to Envarsus XR

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

Group Type ACTIVE_COMPARATOR

Tacrolimus Extended Release Oral Tablet [Envarsus]

Intervention Type DRUG

Switching from current version of tacrolimus to the extended release, once a day version (Envarsus) and titrating dose to achieve an optimal trough level. 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.

Arm 2 - plasma exchange and IVIG

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.

Group Type ACTIVE_COMPARATOR

Plasma Exchange and IVIG (Intravenous Immunoglobulin )

Intervention Type OTHER

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.

Interventions

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Tacrolimus Extended Release Oral Tablet [Envarsus]

Switching from current version of tacrolimus to the extended release, once a day version (Envarsus) and titrating dose to achieve an optimal trough level. 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.

Intervention Type DRUG

Plasma Exchange and IVIG (Intravenous Immunoglobulin )

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.

Intervention Type OTHER

Other Intervention Names

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Envarsus XR

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Veloxis Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James Cooper, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Scott Davis, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Countries

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United States

Other Identifiers

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17-1812

Identifier Type: -

Identifier Source: org_study_id