Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation
This trial is active, not recruiting.
|Condition||kidney; complications, allograft|
|Start date||March 2011|
|End date||September 2014|
|Trial size||16 participants|
|Trial identifier||NCT01327573, AI-EC-0017|
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.
|Endpoint classification||efficacy study|
|Intervention model||parallel assignment|
Percent change in GFR
time frame: baseline, 6 months
Number of circulating endothelial cells with evidence of injury and bound antibody and/or complement
time frame: baseline, 3,6,9 months
Number of endothelial expressed genes that correlate with humoral rejection
time frame: baseline, 3,6,9 months
Change in GFR
time frame: Baseline, 3,6,9,12 months
time frame: baseline, 3,6,9,12 month
Male or female participants from 18 years up to 65 years old.
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
|Official title||Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation: A Randomized, Open-Label, Pilot Intervention Trial|
|Principal investigator||Sanjay Kulkarni, MD|
|Description||This study will address the clinical challenge that currently exists in the management of kidney transplant recipients who have developed de novo DSA, have deteriorating graft function, yet have no established treatment alternative. This is a randomized, open-label, pilot intervention trial. Post transplant patients with deteriorating renal function (defined as 20% reduction in GFR) will be screened for the development of DSA and biopsied for the presence of C4d deposition. All patients with DSA and those meeting inclusion/exclusion criteria will undergo protocol renal biopsy and will be assessed for C4d deposition. Participants will be randomized to treatment with eculizumab plus standard of care (SOC) or SOC only. Randomization will be stratified by C4d status (C4d+/C4d-) with 10 subjects (7 eculizumab, 3 SOC only) in each stratum. Eculizumab is an antibody that has been developed to inhibit the complement protein C5. Eculizumab will be delivered via IV according to the following schedule: - Eculizumab Induction 600mg IV every 7 days for 4 doses - Eculizumab 900mg IV 7 days later - Eculizumab Maintenance 900mg IV every 14 days for total of 26 weeks|
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