Belatacept Conversion in Proteinuric Kidney Transplant Recipients

NCT02327403 | Completed Phase 2 Results

• 1 other identifier: 2015P000154
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Proteinuria

Keywords

Proteinuria; Kidney transplantation; Allograft dysfunction; B7-1; Belatacept

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• Change in Renal Function (eGFR in mL/Min/1.73 m^2)

  from baseline to 12 months

• Acute Rejection Episodes

  12 months

• Change in Blood Pressure Measurement (mm Hg)

  12 months

• Change in Fasting Glucose

  12 months

• Hyperlipidemia

  12 months

Study Arms (1)

Proteinuric Kidney Transplant Recipients

EXPERIMENTAL

Belatacept conversion

Drug: Belatacept

Interventions

Belatacept DRUG

Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.

Proteinuric Kidney Transplant Recipients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Proteinuria

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Dr. Leonardo V Riella, MD, PhD
• Organization: Massachusetts General Hospital

LRIELLA@MGH.HARVARD.EDU

6176436266

Study Officials

• Leonardo V Riella, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 22, 2014
• First Posted: December 30, 2014
• Study Start: October 1, 2015
• Primary Completion: September 1, 2020
• Study Completion: October 1, 2020
• Last Updated: November 9, 2022
• Results First Posted: November 9, 2022

Record last verified: 2022-10

Locations

US (1)