Belatacept Conversion in Proteinuric Kidney Transplant Recipients

NCT ID: NCT02327403

Last Updated: 2022-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2020-10-01

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.

Conditions

Proteinuria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Proteinuric Kidney Transplant Recipients

Belatacept conversion

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.

Interventions

Belatacept

Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Leonardo V. Riella, MD PhD

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Leonardo V Riella, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015P000154

Identifier Type: -

Identifier Source: org_study_id