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Kidney Transplant RejectionEarly Phase 1NCT03380936

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

A Early Phase 1 study testing Tacrolimus Extended Release Oral Tablet [Envarsus] and Plasma Exchange and IVIG (Intravenous Immunoglobulin ) in people with Kidney Transplant Rejection, run by University of Colorado, Denver at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 79 years
Conditions the study is for
Kidney Transplant Rejection
What is being tested?
Tacrolimus Extended Release Oral Tablet [Envarsus] and Plasma Exchange and IVIG (Intravenous Immunoglobulin )
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
17 Jan 2018to 16 Oct 2019
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

United States1 site

  • University of Colorado Anschutz Medical Campus

    Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Tacrolimus Extended Release Oral Tablet [Envarsus], Plasma Exchange and IVIG (Intravenous Immunoglobulin )
Keywords
subclinical, graft rejection, AMR (antibody-mediated rejection), AMBR (acute antibody-mediated rejection), DSA (donor specific antibodies)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tacrolimus Extended Release Oral Tablet [Envarsus]Drug

    Also called Envarsus XR

    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.

  • Plasma Exchange and IVIG (Intravenous Immunoglobulin )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.

Study groups in NCT03380936
Study groupRoleWhat they receive
Arm 1 - conversion to Envarsus XRActive comparatorOptimize: 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
Receives: Drug: Tacrolimus Extended Release Oral Tablet [Envarsus]
Arm 2 - plasma exchange and IVIGActive comparatorTreat 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.
Receives: Other: Plasma Exchange and IVIG (Intravenous Immunoglobulin )

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Acute Inflammatory Histologic Parameters

    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.

    Measured: Baseline and 6 months

Secondary outcomes (6)

  1. Change in MDRD GFR (Modification of Diet in Renal Disease Glomerular Filtration Rate)

    Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.

    Measured: 6 and 12 months

  2. Change in Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI) Level

    Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.

    Measured: 6 and 12 months

  3. Change in serum creatinine

    Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.

    Measured: 6 and 12 months

  4. Graft Survival

    Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests.

    Measured: 6 and 12 months

  5. Patient Survival

    Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests.

    Measured: 6 and 12 months

  6. Evaluation of Adverse Events

    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.

    Measured: 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2017
  2. Study start17 Jan 2018
  3. Primary completion16 Oct 2019
  4. Study completion16 Oct 2019

Why it stopped: Slower than expected recruitment rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03380936
Sponsor's protocol ID
17-1812
Status last verified
Oct 2020
First submitted
26 Oct 2017
Last updated
27 Oct 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Tacrolimus Extended Release Oral Tablet [Envarsus] and Plasma Exchange and IVIG (Intravenous Immunoglobulin ) in people with Kidney Transplant Rejection, run by University of Colorado, Denver at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slower than expected recruitment rate). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Acute Inflammatory Histologic Parameters (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03380936.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2020.

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