Switch From Calcineurin Inhibitor to Belatacept in Pancreas Transplant Recipients

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02103855
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 21
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nephrotoxicity	Drug: Belatacept	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Calcineurin Inhibitors to Belatacept Switch Study to Prevent the Progression of Kidney Disease in Pancreas Transplant Alone Recipients
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR) [Baseline and 1 year]

   Change in serum eGFR from baseline to 1 year following conversion from tacrolimus to belatacept

2. Serum Creatinine at Year 1 [1 year]

   Serum Creatinine measured at 1 year after conversion from Tacrolimus to Belatacept.

Secondary Outcome Measures

1. Number of Participants With Pancreas Transplant Rejection [1 year]

   Pancreas Rejection as measured by serum amylase, serum lipase.

2. Change From Baseline Serum Hemoglobin A1c [Baseline and 1 year]

   Pancreas Transplant Function was measured by assessing change in Pre HbA1c to Post HbA1c at1 year after conversion.

3. Pancreas Transplant Function as Measured by Fasting Serum Glucose Level. [1 Year]

   Fasting Serum Glucose level measured at 1 year after conversion from Tacrolimus to Belatacept.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Health, University Hospital	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Asif Sharfuddin, Asif A Sharfuddin, MD, Indiana University
• ClinicalTrials.gov Identifier: NCT02103855
• Other Study ID Numbers: BMS 103-337
• First Posted: Apr 4, 2014
• Last Update Posted: Aug 28, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Asif Sharfuddin, Asif A Sharfuddin, MD, Indiana University: pancreas transplantation; immunosuppression; belatacept
• Additional relevant MeSH terms: Abatacept

Study Results

Participant Flow

Recruitment Details	First patient enrolled and started on June 3, 2014. Last patient enrolled and started on Aug 6, 2014. All patients enrolled at Indiana University Hospital - Transplant Unit.
Pre-assignment Detail	Participants were enrolled according to inclusion and exclusion criteria. Tacrolimus was weaned according to protocol.

Arm/Group Title	Belatacept
Arm/Group Description	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. Belatacept
Period Title: Overall Study
STARTED	6
COMPLETED	4
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Belatacept
Arm/Group Description	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. Belatacept
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	5 83.3%
Male	1 16.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 16.7%
White	5 83.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR)
Description	Change in serum eGFR from baseline to 1 year following conversion from tacrolimus to belatacept
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belatacept
Arm/Group Description	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. Belatacept
Measure Participants	4
Mean (Standard Deviation) [ml/min/1.73m2]	2.25 (3.35)

2. Primary Outcome

Title	Serum Creatinine at Year 1
Description	Serum Creatinine measured at 1 year after conversion from Tacrolimus to Belatacept.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

4 subjects who completed 1 year of Belatacept were analyzed.

Arm/Group Title	Belatacept
Arm/Group Description	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. Belatacept
Measure Participants	4
Mean (Standard Deviation) [mg/dl]	1.8 (0.2)

3. Secondary Outcome

Title	Number of Participants With Pancreas Transplant Rejection
Description	Pancreas Rejection as measured by serum amylase, serum lipase.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belatacept
Arm/Group Description	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. Belatacept
Measure Participants	4
Count of Participants [Participants]	2 33.3%

4. Secondary Outcome

Title	Change From Baseline Serum Hemoglobin A1c
Description	Pancreas Transplant Function was measured by assessing change in Pre HbA1c to Post HbA1c at1 year after conversion.
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belatacept
Arm/Group Description	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. Belatacept
Measure Participants	6
Mean (Standard Deviation) [percentage of glycosylated hemoglobin]	5.9 (0.15)

5. Secondary Outcome

Title	Pancreas Transplant Function as Measured by Fasting Serum Glucose Level.
Description	Fasting Serum Glucose level measured at 1 year after conversion from Tacrolimus to Belatacept.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

4 subjects who completed 1 year of Belatacept.

Arm/Group Title	Belatacept
Arm/Group Description	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. Belatacept
Measure Participants	4
Mean (Standard Deviation) [mg/dl]	96.9 (6.3)

Adverse Events

Arm/Group Title	Belatacept
Arm/Group Description	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. Belatacept
All Cause Mortality
	Belatacept
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Belatacept
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Blood and lymphatic system disorders
Anemia	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	Belatacept
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Anemia	3/6 (50%)	3
Cardiac disorders
Hypertension	2/6 (33.3%)	2
Endocrine disorders
Hyperlipidemia	1/6 (16.7%)	1
Hot Flash	1/6 (16.7%)	1
Eye disorders
Retinal Vessel Rupture	1/6 (16.7%)	1
Gastrointestinal disorders
Nausea	5/6 (83.3%)	5
Infections and infestations
Infection	3/6 (50%)	3
Renal and urinary disorders
Hypokalemia	1/6 (16.7%)	1
Dehydration	1/6 (16.7%)	2
Skin and subcutaneous tissue disorders
Skin Sores	1/6 (16.7%)	1
Hair Loss	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.