Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation: A Randomized, Open-Label, Pilot Intervention Trial|
- Percent change in GFR [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]Percent change is calculated as the 6-month GFR minus the baseline GFR, divided by the baseline GFR Percent change will be compared between treatment groups with stratification by C4d status
- Number of circulating endothelial cells with evidence of injury and bound antibody and/or complement [ Time Frame: baseline, 3,6,9 months ] [ Designated as safety issue: No ]mixed effects model to compare trajectory of in number of circulation endothelial cells with evidence of injury and bound antibody and/or complement between treatment groups
- Number of endothelial expressed genes that correlate with humoral rejection [ Time Frame: baseline, 3,6,9 months ] [ Designated as safety issue: No ]mixed effects models to compare trajectory of number of endothelial expressed genes that correlate with humoral rejection between treatment groups
- Change in GFR [ Time Frame: Baseline, 3,6,9,12 months ] [ Designated as safety issue: No ]Compare trajectories of GFR change and percent GFR change between treatment groups using repeated GFR measurements
- Safety Analysis [ Time Frame: baseline, 3,6,9,12 month ] [ Designated as safety issue: Yes ]Tabulation of treatment-emergent adverse events (categorical) by treatment group as well as evaluation of changes in laboratory parameters (CBC, chemistries) (continuous)
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus, MMF [mycophenolate mofetil
No Intervention: no additional therapy
patients in this arm will receive standard immunosuppression regimen (oral tacrolimus, MMF, prednisone only, no additional therapy
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
|United States, Connecticut|
|New Haven, Connecticut, United States, 06520|
|Contact: Sanjay Kulkarni, MD 203-785-2565|
|Contact: Ricarda Tomlin, BS email@example.com|
|Principal Investigator: Sanjay Kulkarni, MD|
|Principal Investigator:||Sanjay Kulkarni, MD||Yale University|