Belatacept Conversion in Proteinuric Kidney Transplant Recipients

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02327403

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Location

Arms

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background: Proteinuria develops in about 30% of kidney transplant recipients and is a strong predictor of graft loss. The amount of proteinuria has a direct correlation with the risk of graft failure. Novel therapies are urgently needed to reduce proteinuria and prevent graft loss in transplant recipients, since ACE inhibitors carry a number of limitations in the transplant setting, including significant reduction in renal function, anemia and hyperkalemia.

Preliminary data: B7-1 is expressed at significant levels in about 10% of kidney allograft biopsies with predominance in patients with proteinuria.

Hypothesis: We hypothesize that B7-1 targeting therapy may reduce proteinuria and improve graft survival in proteinuric transplant recipients that have B7-1 staining on allografts. In addition, the absence of CNI nephrotoxicity and the potential protective effect of Belatacept on DSA production may be of benefit in this subset of transplant patients.

Objectives:

Primary: Determine the effect of Belatacept conversion in reducing proteinuria by 25% at 12 months in renal transplant recipients (≥1gram/d) that are either B7-1-positive or negative on kidney biopsy.

Secondary: Assess the effect of Belatacept conversion in the percent change of renal function from baseline to 12 months; donor-specific anti-HLA antibodies presence and intensity (MFI); correlation of B7-1 positivity on immunofluorescence on biopsy with B7-1-expression in urine extracellular vesicles; adverse events; acute rejection episodes; blood pressure control; new onset diabetes; hyperlipidemia; graft survival; and patient survival.

Condition or Disease	Intervention/Treatment	Phase
Proteinuria	Drug: Belatacept	Phase 2

Detailed Description

A total of 36 patients will be recruited.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The B7-1 Study": Belatacept Conversion in Proteinuric Renal Transplant Recipients: an Interventional Multi-Center Trial

Actual Study Start Date :

Oct 1, 2015

Actual Primary Completion Date :

Sep 1, 2020

Actual Study Completion Date :

Oct 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: B7-1 positivity on kidney allograft biopsy Belatacept conversion	Drug: Belatacept Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.
Active Comparator: B7-1 negativity on kidney allograft biopsy Belatacept conversion	Drug: Belatacept Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.

Arm

Intervention/Treatment

Active Comparator: B7-1 positivity on kidney allograft biopsy

Belatacept conversion

Drug: Belatacept

Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.

Active Comparator: B7-1 negativity on kidney allograft biopsy

Belatacept conversion

Drug: Belatacept

Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.

Outcome Measures

Primary Outcome Measures

Change in Proteinuria by 25% [12 months]

Secondary Outcome Measures

Percent change of renal function (Creatinine in mg/dl and eGFR in ml/min) [from baseline to 12 months]
Change in number and mean-fluoroscence intensity of donor-specific anti-HLA antibodies (DSA) [12 months]
Correlation of B7-1 positivity on immunofluorescence on biopsy (grade 1-3) with B7-1-expression in urine extracellular vesicles (mean-fluoroscence intensity) [12 months]
Acute rejection episodes [12 months]
Change in Blood pressure measurement (mm Hg) [12 months]
New onset diabetes [12 months]
Hyperlipidemia [12 months]
Graft survival [12 months]
Patient survival [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female adult kidney transplant recipients older than 18 years old
eGFR ≥30 ml/min
≥6 months after transplantation
Proteinuria ≥1 gram/day in spot urine protein/creatinine ratio
Ability to provide written informed consent for the study.
Maintenance immunosuppression of CNI (cyclosporine or tacrolimus), antiproliferative agent (azathioprine, MMF or MPA) with either steroids or not.

Exclusion Criteria:

Age <18 years
eGFR<30 ml/min
active acute cellular rejection (ACR; higher than borderline) or ACR in the previous 6 months; active acute antibody-mediated rejection
recurrent FSGS
EBV IgG negative
patient on mTOR inhibitor (e.g. Everolimus, Sirolimus)
patient only on CNI (cyclosporine or tacrolimus) and steroids