Switch From Calcineurin Inhibitor to Belatacept in Pancreas Transplant Recipients

Calcineurin Inhibitors to Belatacept Switch Study to Prevent the Progression of Kidney Disease in Pancreas Transplant Alone Recipients

Kidney damage is a major complication of current antirejection medicines used in transplantation. An increasing number of brittle diabetics are successfully receiving a pancreas transplant. One of the challenges following pancreas transplant is that a patient can develop kidney damage from one of their antirejection medicines, tacrolimus. The objective of this study is to substitute a new antirejection medicine which does not cause kidney damage, belatacept for tacrolimus in patients that have developed signs of tacrolimus related kidney damage to slow the progression of kidney disease.

Study Overview

• Status: Completed
• Conditions: Nephrotoxicity
• Intervention / Treatment: Drug: Belatacept

Detailed Description

Nephrotoxicity is a major complication of current immunosuppression regimens used in transplantation. Pancreas transplantation has been increasedly performed to manage labile diabetes mellitus during the last few decades and survival rates of pancreatic grafts are improving. One of the challenges that is faced following pancreas transplantation alone are pathologic changes from diabetes frequently seen in native kidneys in the pancreas transplant recipients. High levels of calcineurin inhibitors (CNI) have been identified as risk factors for decline in kidney function and progression to end-stage renal disease. The objective of this trial is to take subjects who have biopsy proven CNI toxicity off of their CNI and begin belatacept, which is not a CNI.

The hypothesis is by switching the pancreas transplant subject with documented CNI kidney toxicity to belatacept will slow the progression of chronic kidney disease.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pancreas transplant alone recipients
• EBV IgG positive
• Biopsy proven calcineurin inhibitor toxicity on native kidney biopsy
• Maintained on a regimen of tacrolimus, sirolimus, mycophenolate

Exclusion Criteria:

• EBV IgG negative
• Not maintained on an immunosuppression regimen that contains tacrolimus
• Unable or unwilling to give informed consent
• Active infection
• History of malignancy post transplant
• Glomerular filtration rate < 15 mL/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: belatacept; Belatacept 5 mg/kg IVPB q 2 wks x 5 doses followed by 5 mg/kg IVPB q month. The belatacept dose will be infused IV over 30 minutes. Day 14: Reduce tacrolimus dose by 25% Day 30: Reduce tacrolimus dose by additional 25% Day 45: Reduce tacrolimus dose by additional 25% Day 60: Stop tacrolimus.	Drug: Belatacept; Other Names: Nulojix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR)	Change in serum eGFR from baseline to 1 year following conversion from tacrolimus to belatacept	Baseline and 1 year
Serum Creatinine at Year 1	Serum Creatinine measured at 1 year after conversion from Tacrolimus to Belatacept.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Pancreas Transplant Rejection	Pancreas Rejection as measured by serum amylase, serum lipase.	1 year
Change From Baseline Serum Hemoglobin A1c	Pancreas Transplant Function was measured by assessing change in Pre HbA1c to Post HbA1c at1 year after conversion.	Baseline and 1 year
Pancreas Transplant Function as Measured by Fasting Serum Glucose Level.	Fasting Serum Glucose level measured at 1 year after conversion from Tacrolimus to Belatacept.	1 Year

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Asif Sharfuddin, MD, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: April 1, 2014
• First Submitted That Met QC Criteria: April 1, 2014
• First Posted (Estimate): April 4, 2014

Study Record Updates

• Last Update Posted (Actual): August 28, 2017
• Last Update Submitted That Met QC Criteria: August 25, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: immunosuppression; belatacept; pancreas transplantation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: BMS 103-337