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Belatacept Conversion in Proteinuric Kidney Transplant Recipients

Primary Purpose

Proteinuria

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Belatacept
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Proteinuria focused on measuring Proteinuria, Kidney transplantation, Allograft dysfunction, B7-1, Belatacept

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Proteinuric Kidney Transplant Recipients

Arm Description

Belatacept conversion

Outcomes

Primary Outcome Measures

Change in Proteinuria by 25%
Change in proteinuria by 25%: daily proteinuria is estimated by spot urine protein (mg/dL) to creatinine (mg/dL) ratio at baseline (before the belatacept conversion) and post-conversion 12 months; and interval % change was calculated by getting the ratio of difference between the two time points to the baseline value.

Secondary Outcome Measures

Change in Renal Function (eGFR in mL/Min/1.73 m^2)
Acute Rejection Episodes
Acute rejection episodes [Time Frame: 12 months]: Number of biopsy-proven rejection episodes from belatacept conversion to post-conversion 12 months.
Change in Blood Pressure Measurement (mm Hg)
Change in Blood pressure measurement (mm Hg) [Time Frame: 12 months]: The mmHg difference in systolic and diastolic blood pressures between the baseline (pre-belatacept conversion) and post-conversion 12 months is assessed. Blood pressure measurement done at the office visits at baseline and 12 months after at least 5 minutes of resting.
Change in Fasting Glucose
New onset diabetes [Time Frame: 12 months]: Number of new onset diabetes per American Diabetes Association 2015 Criteria from belatacept conversion to post-conversion 12 months
Hyperlipidemia
Hyperlipidemia [ Time Frame: 12 months]: Changes (mg/dL) in serum total cholesterol, LDL, HDL, and triglyceride levels from pre-belatacept conversion to post-conversion 12 months.
Graft Survival
Graft survival [Time Frame: 12 months]: Number of patients who developed end stage kidney disease and required kidney replacement therapy within 12 months post-belatacept conversion.
Patient Survival

Full Information

First Posted
December 22, 2014
Last Updated
October 17, 2022
Sponsor
Brigham and Women's Hospital
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02327403
Brief Title
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

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
October 2015 (Actual)
Primary Completion Date
September 2020 (Actual)
Study Completion Date
October 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. 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.
Detailed Description
A total of 36 patients will be recruited.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Proteinuria
Keywords
Proteinuria, Kidney transplantation, Allograft dysfunction, B7-1, Belatacept

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Proteinuric Kidney Transplant Recipients
Arm Type
Experimental
Arm Description
Belatacept conversion
Intervention Type
Drug
Intervention Name(s)
Belatacept
Intervention Description
Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.
Primary Outcome Measure Information:
Title
Change in Proteinuria by 25%
Description
Change in proteinuria by 25%: daily proteinuria is estimated by spot urine protein (mg/dL) to creatinine (mg/dL) ratio at baseline (before the belatacept conversion) and post-conversion 12 months; and interval % change was calculated by getting the ratio of difference between the two time points to the baseline value.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change in Renal Function (eGFR in mL/Min/1.73 m^2)
Time Frame
from baseline to 12 months
Title
Acute Rejection Episodes
Description
Acute rejection episodes [Time Frame: 12 months]: Number of biopsy-proven rejection episodes from belatacept conversion to post-conversion 12 months.
Time Frame
12 months
Title
Change in Blood Pressure Measurement (mm Hg)
Description
Change in Blood pressure measurement (mm Hg) [Time Frame: 12 months]: The mmHg difference in systolic and diastolic blood pressures between the baseline (pre-belatacept conversion) and post-conversion 12 months is assessed. Blood pressure measurement done at the office visits at baseline and 12 months after at least 5 minutes of resting.
Time Frame
12 months
Title
Change in Fasting Glucose
Description
New onset diabetes [Time Frame: 12 months]: Number of new onset diabetes per American Diabetes Association 2015 Criteria from belatacept conversion to post-conversion 12 months
Time Frame
12 months
Title
Hyperlipidemia
Description
Hyperlipidemia [ Time Frame: 12 months]: Changes (mg/dL) in serum total cholesterol, LDL, HDL, and triglyceride levels from pre-belatacept conversion to post-conversion 12 months.
Time Frame
12 months
Title
Graft Survival
Description
Graft survival [Time Frame: 12 months]: Number of patients who developed end stage kidney disease and required kidney replacement therapy within 12 months post-belatacept conversion.
Time Frame
12 months
Title
Patient Survival
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leonardo V Riella, MD, PhD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

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Belatacept Conversion in Proteinuric Kidney Transplant Recipients

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