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

NCT03380936 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: 17-1812
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplant Rejection

Keywords

subclinical; graft rejection; AMR (antibody-mediated rejection); AMBR (acute antibody-mediated rejection); DSA (donor specific antibodies)

Outcome Measures

Primary Outcomes (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.

  Baseline and 6 months

Secondary Outcomes (6)

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

  6 and 12 months

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

  6 and 12 months

• Change in serum creatinine

  6 and 12 months

• Graft Survival

  6 and 12 months

• Patient Survival

  6 and 12 months

Study Arms (2)

Arm 1 - conversion to Envarsus XR

ACTIVE COMPARATOR

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]

Arm 2 - plasma exchange and IVIG

ACTIVE COMPARATOR

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 )

Interventions

Tacrolimus Extended Release Oral Tablet [Envarsus] 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.

Also known as: Envarsus XR

Arm 1 - conversion to Envarsus XR

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.

Arm 2 - plasma exchange and IVIG

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Veloxis Pharmaceuticals: collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Interventions

Tacrolimus; Plasma Exchange; Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• James Cooper, M.D.

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Scott Davis, M.D.

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 26, 2017
• First Posted: December 21, 2017
• Study Start: January 17, 2018
• Primary Completion: October 16, 2019
• Study Completion: October 16, 2019
• Last Updated: October 27, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)