Clinical trial NCT02327403: Belatacept Conversion in Proteinuric Kidney Transplant Recipients
Official title: The B7-1 Study": Belatacept Conversion in Proteinuric Renal Transplant Recipients: an Interventional Multi-Center Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Proteinuria
Keywords: Proteinuria
Kidney transplantation
Allograft dysfunction
B7-1
Belatacept
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2014-12-30
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: A total of 36 patients will be recruited.

Eligibility criteria: Inclusion Criteria:

1. Male or female adult kidney transplant recipients older than 18 years old
2. eGFR ≥30 ml/min
3. ≥6 months after transplantation
4. Proteinuria ≥1 gram/day in spot urine protein/creatinine ratio
5. Ability to provide written informed consent for the study.
6. Maintenance immunosuppression of CNI (cyclosporine or tacrolimus), antiproliferative agent (azathioprine, MMF or MPA) with either steroids or not.

Exclusion Criteria:

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

Primary outcomes:
measure: Change in Proteinuria by 25%
timeFrame: 12 months
Secondary outcomes:
measure: Change in Renal Function (eGFR in mL/Min/1.73 m^2)
timeFrame: from baseline to 12 months
measure: Acute Rejection Episodes
timeFrame: 12 months
measure: Change in Blood Pressure Measurement (mm Hg)
timeFrame: 12 months
measure: Change in Fasting Glucose
timeFrame: 12 months
measure: Hyperlipidemia
timeFrame: 12 months
measure: Graft Survival
timeFrame: 12 months
measure: Patient Survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Leonardo V Riella, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: