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

Kidney Transplant Rejection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03380936
• Other study ID #: 17-1812
• Status: Terminated
• Phase: Early Phase 1
• Start date: January 17, 2018
• Est. completion date: October 16, 2019

Study information

• Verified date: October 2020
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: October 16, 2019
• Est. primary completion date: October 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

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:
• 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.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Veloxis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and 6 months
Secondary	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.	6 and 12 months
Secondary	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.	6 and 12 months
Secondary	Change in serum creatinine	Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.	6 and 12 months
Secondary	Graft Survival	Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests.	6 and 12 months
Secondary	Patient Survival	Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests.	6 and 12 months
Secondary	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.	6 and 12 months