NCT02130817

Belatacept in Kidney Transplantation of Moderately Sensitized Patients

Belatacept for the Management of Moderately Sensitized Patients at Risk for Delayed Graft Function (DGF)

• Status: Withdrawn
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the safety and effectiveness of an immunosuppressive medication, Belatacept, as a replacement for a calcineurin inhibitor, in combination with a standard of care regimen of immunosuppressive medications and plasma exchange (plasmapheresis and immunoglobulin treatment) for kidney transplant patients who are moderately sensitized against their deceased donor and at-risk for delayed graft function. The hypothesis is that moderately sensitized patients who receive Belatacept treatment with the standard of care regimen will lead to lower acute rejection rates than historical controls based on assessment of standard of care biopsies and standard Banff criteria.

Detailed description

This exploratory single-center, open-label safety and efficacy study will enroll 20 adult kidney transplants candidates, moderately sensitized against their deceased donor and at-risk for delayed graft function (DGF), to receive Belatacept (days 0,5, weeks 2,4,8 and 12 (10 mg/kg), and every 4 weeks thereafter (5 mg/kg)), plasma exchange (once before and twice after transplant) and Intravenous Immunoglobulin (IVIG) (100 mg/kg after each plasma exchange), along with Thymoglobulin (ATG) induction and Dexamethasone tapered dosing starting on the day of transplant at 100mg IV, tapered through Day 4, followed by prednisone at 30 mg on Day 5 with tapered dosing to prednisone 10 mg/d by one month, with a total observation period of 1 year. Patients will be tapered off tacrolimus by week 8 and will remain on mycophenolic acid and prednisone for the total length of the study. Subjects will be followed until 1 year post transplant.

Conditions

• End Stage Renal Disease
• Antibody Mediated Rejection

Interventions

Type	Name	Description
DRUG	Belatacept	Belatacept will be added to the standard of care regimen and will be given at days 0,5, weeks 2, 4, 8 and 12 (10 mg/kg) and every 4 weeks (5 mg/kg) for one year.
DRUG	Tacrolimus withdrawal	Tacrolimus dosing will begin on Days 1 through 5 post transplant at up to 2 mg BID to achieve target trough levels of 9-11 ng/ml. The dose will be tapered through the end of week 2 to achieve a trough level of 4 ng/ml which will be maintained for six weeks. Tacrolimus will be withdrawn at the end of eight weeks post transplant.
PROCEDURE	Plasmapheresis/Intravenous Immunoglobulin G	Enrolled patients will start with standard of practice treatment including plasmapheresis and IVIG therapy twice after transplant, on days 2 and 4 and potentially once before transplant. Plasmapheresis and albumin exchange for one volume of blood will be performed in the infusion center at the University of Wisconsin Hospital and Clinics (UWHC). Each pheresis session will be completed by IVIG infusion. While plasmapheresis will help with the removal of circulating Donor Specific Antibodies (DSA), IVIG therapy will provide immunomodulatory characteristics that include sterilizing immunity from infections, inhibiting and scavenging activated complement fragments, modifying cell-mediated immune responses, inducing regulatory T cells and importantly, inhibiting deleterious antibody production.
DRUG	Thymoglobulin (ATG)	Thymoglobulin (ATG) Induction. Thymoglobulin will be administered to a total cumulative dose of 4.5-6 mg/kg via a peripheral or central vein, starting in the operating room.
DRUG	Myfortic	Patients will receive 720mg bid of Myfortic throughout the study, starting day 1 after surgery.
DRUG	Steroids	Patients will receive Dexamethasone IV on the day of surgery (Day 0) with tapered doses through Day 4 followed by prednisone tapered to 10mg/d by day 30.,

Timeline

• Start date: 2014-09-24
• Primary completion: 2015-10-09
• Completion: 2015-10-09
• First posted: 2014-05-05
• Last updated: 2018-12-17

Locations

1 site across 1 country: United States