Safety & Tolerability of Berinert® (C1 Inhibitor) Therapy to Prevent Rejection

Summary

Organ transplantation offers the only hope for a normal life for patients with end-stage renal disease on dialysis (ESRD). For the highly-sensitized patient, patients with antibodies to human leukocyte antigens (HLA), transplantation is extremely difficult or impossible since pre-formed antibodies will cause severe rejection and loss of transplanted organs. Approximately 30% of the transplant list in the U.S. is considered sensitized (have detectable antibodies to HLA antigens). These anti-HLA (anti-Human Leukocyte Antigen antibodies) pose a significant barrier to transplantation that has recently been successfully addressed using desensitization therapies with IVIG, rituximab and/or plasmapheresis (PE). Despite the success of these therapies, post-transplant antibody mediated rejection (AMR) and chronic Antibody Mediated Rejection (CAMR) remain significant problems. Recent data suggests that addition of Berinert (C1 Inhibitor) to post-transplant treatment regimen may significantly reduce incidence of Antibody Mediation Rejection. Twenty highly-sensitized patients who have undergone desensitization treatment and are awaiting kidney transplant will be enrolled in the study. Once transplanted these patients will be started on the standard of care post-transplant immunosuppressive protocol. In addition patients will receive Berinert 20 units/ kg daily x 3 days, then twice weekly x 3 weeks. At the end of Berinert treatment a kidney biopsy will be performed. Subjects will be followed for 6 months to assess safety and efficacy of the study protocol.

Timeline

Start

2011-08

Primary completion

2013-11

Completion

2013-11

Publications

• Background Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008 Jul 17;359(3):242-51. doi: 10.1056/NEJMoa0707894.
• Background Jordan SC, Tyan D, Stablein D, McIntosh M, Rose S, Vo A, Toyoda M, Davis C, Shapiro R, Adey D, Milliner D, Graff R, Steiner R, Ciancio G, Sahney S, Light J. Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial. J Am Soc Nephrol. 2004 Dec;15(12):3256-62. doi: 10.1097/01.ASN.0000145878.92906.9F.
• Background Jordan SC, Reinsmoen N, Peng A, Lai CH, Cao K, Villicana R, Toyoda M, Kahwaji J, Vo AA. Advances in diagnosing and managing antibody-mediated rejection. Pediatr Nephrol. 2010 Oct;25(10):2035-45; quiz 2045-8. doi: 10.1007/s00467-009-1386-4. Epub 2010 Jan 14.
• Background Solez K, Colvin RB, Racusen LC, Sis B, Halloran PF, Birk PE, Campbell PM, Cascalho M, Collins AB, Demetris AJ, Drachenberg CB, Gibson IW, Grimm PC, Haas M, Lerut E, Liapis H, Mannon RB, Marcus PB, Mengel M, Mihatsch MJ, Nankivell BJ, Nickeleit V, Papadimitriou JC, Platt JL, Randhawa P, Roberts I, Salinas-Madriga L, Salomon DR, Seron D, Sheaff M, Weening JJ. Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). Am J Transplant. 2007 Mar;7(3):518-26. doi: 10.1111/j.1600-6143.2006.01688.x.
• Background Shapiro R. Reducing antibody levels in patients undergoing transplantation. N Engl J Med. 2008 Jul 17;359(3):305-6. doi: 10.1056/NEJMe0804275. No abstract available.
• Results Vo AA, Zeevi A, Choi J, Cisneros K, Toyoda M, Kahwaji J, Peng A, Villicana R, Puliyanda D, Reinsmoen N, Haas M, Jordan SC. A phase I/II placebo-controlled trial of C1-inhibitor for prevention of antibody-mediated rejection in HLA sensitized patients. Transplantation. 2015 Feb;99(2):299-308. doi: 10.1097/TP.0000000000000592.

Drugs

Indications

No indication recorded.