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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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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.
A total of 36 patients will be recruited.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Proteinuric Kidney Transplant Recipients | Experimental | Belatacept conversion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Belatacept | Drug | Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Renal Function (eGFR in mL/Min/1.73 m^2) | from baseline to 12 months | |
| Acute Rejection Episodes | Acute rejection episodes [Time Frame: 12 months]: Number of biopsy-proven rejection episodes from belatacept conversion to post-conversion 12 months. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Leonardo V Riella, MD, PhD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Belatacept Conversion | Kidney Transplant recipients with proteinuria who converted their immunosuppression from CNI to belatacept-based maintenance therapy |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Belatacept Conversion | Belatacept: Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 12 months |
|
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Belatacept Conversion | Kidney Transplant recipients with proteinuria who converted their immunosuppression from CNI to belatacept-based maintenance therapy |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac Arrest | Cardiac disorders | Non-systematic Assessment | Cardiac arrest leading to death |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Leonardo V Riella, MD, PhD | Massachusetts General Hospital | 6176436266 | LRIELLA@MGH.HARVARD.EDU |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 9, 2019 | Aug 17, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011507 | Proteinuria |
| ID | Term |
|---|---|
| D014555 | Urination Disorders |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| D000069594 | Abatacept |
| ID | Term |
|---|---|
| D018796 | Immunoconjugates |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D012712 | Serum Globulins |
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| 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. | 12 months |
| 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 | 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. | 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. | 12 months |
| Patient Survival | 12 months |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Change in Renal Function (eGFR in mL/Min/1.73 m^2) | Posted | Mean | Standard Deviation | mL/min/1.73m2 | from baseline to 12 months |
|
|
|
| Secondary | Acute Rejection Episodes | Acute rejection episodes [Time Frame: 12 months]: Number of biopsy-proven rejection episodes from belatacept conversion to post-conversion 12 months. | Posted | Number | episodes | 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | mmHg | 12 months |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | mg/dL | 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | mg/dL | 12 months |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Patient Survival | Posted | Count of Participants | Participants | 12 months |
|
|
|
| 1 |
| 15 |
| 1 |
| 15 |
| 9 |
| 15 |
|
| Shingles | Infections and infestations | Non-systematic Assessment |
|
| MRSA Cellulitis with Abscess | Infections and infestations | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | Non-systematic Assessment |
|
| Pyelonephritis | Infections and infestations | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | Non-systematic Assessment |
|
| Acute Kidney Injury | Renal and urinary disorders | Non-systematic Assessment | Due to interstitial inflammation |
|
| Syncope | Nervous system disorders | Non-systematic Assessment |
|
| Basal Cell Carcinoma | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Recurrence of Bladder Tumor | Renal and urinary disorders | Non-systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
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| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D005916 | Globulins |
| Title | Measurements |
|---|---|
|
| 12 Months (Diastolic) |
|