A Phase I/II Placebo-Controlled Trial of C1-Inhibitor for Prevention of Antibody-Mediated
Vo AA, Zeevi A, et al.Transplantation 2015 99(2): 299-308
Aims
Investigate the safety and efficacy of human C1-inhibitor (C1-INH) to prevent antibody medicated rejection (AMR) using a phase I/II exploratory trial design.
Interventions
C1-INH (20 IU/kg/dose) versus placebo (normal saline) was administered intraoperatively and then twice weekly for 7 additional doses. All patients received alemtuzumab for induction and tacrolimus, mycophenolic acid, and prednisone as maintenance immunosuppression.
Participants
20 adult, highly sensitised renal transplant recipients who received an incompatible transplant after desensitization with intravenous immune globulin, rituximab with or without plasma exchange.
Outcomes
The primary outcome was the incidence of AMR at 1 and 6 months. Other outcomes were risk for AMR, graft and patient survival, renal function, infectious complications, C1q+ donor specific antibodies (DSA) levels after transplantation and (serious) adverse events. Protocol biopsies were performed and graded by Banff criteria.
Follow-up
6 months
CET Conclusions
This is a phase I trial of C1-inhibitor for prevention of antibody mediated rejection in HLA sensitized patients. All these patients were highly sensitized and were desensitized with IVIG, rituximab and/or plasmapheresis. The patients were randomised to receive either a C1 inhibitor or a placebo intraoperatively and then twice weekly for 7 doses. There were no serious adverse events related to the administration of the C1 inhibitor or the placebo. There was a suggestion that there was less antibody mediated rejection in the patients who received the C1inhibitor. This might prove a useful exercise for the management of highly sensitized patients as an addition to desensitization but obviously much larger studies are required. This is important as we begin to see the introduction of complement inhibitors into the clinic.
Data analysis
Available case analysis
Trial registration
ClinicalTrials.gov - NCT01134510