Clinical trial NCT03380936: Pilot Study of Treatment for Subclinical AMR (Antibody-mediated Rejection) in Kidney Transplant Recipients
Official title: A Randomized Pilot Study of Treatment for Subclinical Antibody-Mediated Rejection in Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Kidney Transplant Rejection
Keywords: subclinical
graft rejection
AMR (antibody-mediated rejection)
AMBR (acute antibody-mediated rejection)
DSA (donor specific antibodies)
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Veloxis Pharmaceuticals
First posted: 2017-12-21
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Acute Inflammatory Histologic Parameters
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Change in MDRD GFR (Modification of Diet in Renal Disease Glomerular Filtration Rate)
timeFrame: 6 and 12 months
measure: Change in Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI) Level
timeFrame: 6 and 12 months
measure: Change in serum creatinine
timeFrame: 6 and 12 months
measure: Graft Survival
timeFrame: 6 and 12 months
measure: Patient Survival
timeFrame: 6 and 12 months
measure: Evaluation of Adverse Events
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: James Cooper, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Scott Davis, M.D.
role: PRINCIPAL_INVESTIGATOR
References: