TY - JOUR
T1 - Plasma-Derived C1 Esterase Inhibitor for Acute Antibody-Mediated Rejection Following Kidney Transplantation
T2 - Results of a Randomized Double-Blind Placebo-Controlled Pilot Study
AU - Montgomery, R. A.
AU - Orandi, B. J.
AU - Racusen, L.
AU - Jackson, A. M.
AU - Garonzik-Wang, J. M.
AU - Shah, T.
AU - Woodle, E. S.
AU - Sommerer, C.
AU - Fitts, D.
AU - Rockich, K.
AU - Zhang, P.
AU - Uknis, M. E.
N1 - Funding Information:
We thank the patients and study personnel who made this study possible. This study was funded by ViroPharma Incorporated, now part of the Shire group of companies. Gayle Scott, PharmD, and Sabrina L. Maurer, PharmD, CMPP, of Excel Scientific Solutions provided assistance in developing the manuscript, which was supported by Shire. Lisa Goldberg ensured compliance with GCP and was the clinical operations lead at ViroPharma for this project.
Publisher Copyright:
© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Antibody-mediated rejection (AMR) is typically treated with plasmapheresis (PP) and intravenous immunoglobulin (standard of care; SOC); however, there is an unmet need for more effective therapy. We report a phase 2b, multicenter double-blind randomized placebo-controlled pilot study to evaluate the use of human plasma-derived C1 esterase inhibitor (C1 INH) as add-on therapy to SOC for AMR. Eighteen patients received 20 000 units of C1 INH or placebo (C1 INH n = 9, placebo n = 9) in divided doses every other day for 2 weeks. No discontinuations, graft losses, deaths, or study drug-related serious adverse events occurred. While the study's primary end point, a difference between groups in day 20 pathology or graft survival, was not achieved, the C1 INH group demonstrated a trend toward sustained improvement in renal function. Six-month biopsies performed in 14 subjects (C1 INH = 7, placebo = 7) showed no transplant glomerulopathy (TG) (PTC+cg≥1b) in the C1 INH group, whereas 3 of 7 placebo subjects had TG. Endogenous C1 INH measured before and after PP demonstrated decreased functional C1 INH serum concentration by 43.3% (p < 0.05) for both cohorts (C1 INH and placebo) associated with PP, although exogenous C1 INH–treated patients achieved supraphysiological levels throughout. This new finding suggests that C1 INH replacement may be useful in the treatment of AMR.
AB - Antibody-mediated rejection (AMR) is typically treated with plasmapheresis (PP) and intravenous immunoglobulin (standard of care; SOC); however, there is an unmet need for more effective therapy. We report a phase 2b, multicenter double-blind randomized placebo-controlled pilot study to evaluate the use of human plasma-derived C1 esterase inhibitor (C1 INH) as add-on therapy to SOC for AMR. Eighteen patients received 20 000 units of C1 INH or placebo (C1 INH n = 9, placebo n = 9) in divided doses every other day for 2 weeks. No discontinuations, graft losses, deaths, or study drug-related serious adverse events occurred. While the study's primary end point, a difference between groups in day 20 pathology or graft survival, was not achieved, the C1 INH group demonstrated a trend toward sustained improvement in renal function. Six-month biopsies performed in 14 subjects (C1 INH = 7, placebo = 7) showed no transplant glomerulopathy (TG) (PTC+cg≥1b) in the C1 INH group, whereas 3 of 7 placebo subjects had TG. Endogenous C1 INH measured before and after PP demonstrated decreased functional C1 INH serum concentration by 43.3% (p < 0.05) for both cohorts (C1 INH and placebo) associated with PP, although exogenous C1 INH–treated patients achieved supraphysiological levels throughout. This new finding suggests that C1 INH replacement may be useful in the treatment of AMR.
KW - clinical research/practice
KW - clinical trial
KW - kidney transplantation/nephrology
KW - rejection: antibody-mediated (ABMR)
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U2 - 10.1111/ajt.13871
DO - 10.1111/ajt.13871
M3 - Article
C2 - 27184779
AN - SCOPUS:84994165600
SN - 1600-6135
VL - 16
SP - 3468
EP - 3478
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 12
ER -