Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is designed to assess the effectiveness of eculizumab in recipients of kidney transplantation with donor-specific antibodies (DSA) and worsening kidney function and to assess if eculizumab improves endothelial cell injury in the kidney.

The investigators hypothesize that complement inhibition with eculizumab will reduce allograft injury, resulting from less complement-mediated injury of endothelial cells and less endothelial cell activation.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanjay Kulkarni
• Collaborator: Alexion Pharmaceuticals
• Treatments: Complement System Proteins; Eculizumab

Criteria

Inclusion Criteria:

• Kidney transplant recipients greater than 6 months from the date of transplant

• Must be on standard immunosuppression: tacrolimus, mycophenolate mofetil, prednisone and have stable tacrolimus trough levels over past 3 months

• Deteriorating renal function, as defined by 20% reduction in GFR (MDRD calculation)

• Presence of DSA, as defined as MFI > 1100

• Renal biopsy demonstrating no diffuse, irreversible end-stage organ injury (i.e. stage IV Fibrosis)

• Renal biopsy demonstrating C4d deposition (stratum 1) or no C4d deposition (stratum 2)

Exclusion Criteria:

• History of CMV, BK, HSV or other viral infections

• History of chronic, recurrent bacterial infections

• Evidence of tubulitis on renal biopsy or other morphological features of acute cellular rejection or acute humoral rejection

• Renal biopsy demonstrating diffuse, irreversible end-stage organ injury

• Absolute GFR < 25 (MDRD calculation)

• Inability to provide informed consent

• History of poor vascular access

• Refusal to use double barrier contraception during study participation

• Patients actively enrolled in other clinical trials