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

October 23, 2020 updated by: University of Colorado, Denver

A Randomized Pilot Study of Treatment for Subclinical Antibody-Mediated Rejection in Kidney Transplant Recipients

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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
Drug: 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.
Other Names:
  • Envarsus XR
Active Comparator: 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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Acute Inflammatory Histologic Parameters
Time Frame: Baseline and 6 months
Any increase or reduction in ptc+g+C4d score by Banff 2013 criteria) from baseline (pre-treatment) to 6 month (post-treatment initiation). Analysis will comprise exact chi-squared tests for comparison of binomial proportions of histological response between the two treatment groups.
Baseline and 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in MDRD GFR (Modification of Diet in Renal Disease Glomerular Filtration Rate)
Time Frame: 6 and 12 months
Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.
6 and 12 months
Change in Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI) Level
Time Frame: 6 and 12 months
Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.
6 and 12 months
Change in serum creatinine
Time Frame: 6 and 12 months
Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.
6 and 12 months
Graft Survival
Time Frame: 6 and 12 months
Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests.
6 and 12 months
Patient Survival
Time Frame: 6 and 12 months
Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests.
6 and 12 months
Evaluation of Adverse Events
Time Frame: 6 and 12 months
All potential adverse events will be captured and recorded by study coordinators during post-treatment standard of care clinic visits, and reviewed by PI. Adverse events will be reported for each group separately and compared using exact chi-squared tests.
6 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Colorado, Denver

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Veloxis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: James Cooper, M.D., University of Colorado, Denver
  • Principal Investigator: Scott Davis, M.D., University of Colorado, Denver

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 17, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 16, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 16, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 26, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 27, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 23, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17-1812

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

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Conditions

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