Overview

This trial is active, not recruiting.

Condition kidney; complications, allograft
Treatment eculizumab
Phase phase 1
Target C5
Sponsor Sanjay Kulkarni
Collaborator Alexion Pharmaceuticals
Start date March 2011
End date September 2014
Trial size 16 participants
Trial identifier NCT01327573, AI-EC-0017

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus, MMF [mycophenolate mofetil ], prednisone)
eculizumab h5G1.1-mAb
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
(No Intervention)
patients in this arm will receive standard immunosuppression regimen (oral tacrolimus, MMF, prednisone only, no additional therapy

Primary Outcomes

Measure
Percent change in GFR
time frame: baseline, 6 months

Secondary Outcomes

Measure
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
Safety Analysis
time frame: baseline, 3,6,9,12 month

Eligibility Criteria

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Yale University.