Trial Information

A Multicenter, Open-Label, Study to Determine the Safety of BG9588 (Anti-CD40L Antibody) Therapy Compared to Standard Treatment in Renal Allograft Transplantation

This protocol is an open label, non-randomized study designed to test whether treatment with
BG9588, a humanized monoclonal antibody specific for CD154, can induce a state of allograft
tolerance following renal allotransplantation in humans. This study is designed to
primarily assess the safety and efficacy of BG9588 when given alone or in combination with
steroids and mycophenolate to prevent renal allograft rejection without the use of
calcineurin inhibitors or other chronic anti-rejection therapies. Efficacy parameters will
include the incidence of acute and chronic rejection episodes, and immunological graft loss.
Additional evaluation will be performed to specifically assess the development of
donor-specific immune hyporesponsiveness resulting from the use of BG9588.

This study is based on extensive use of BG9588 in non-human primates and pilot evaluation in
humans. Up to five patients in each group receiving primary renal allografts will be
treated with a 12-month course of BG9588 with or without steroids and mycophenolate to
prevent allograft rejection. The recruitment will be performed first in the group with
steroids and mycophenolate. Subjects will receive BG9588 at a dose of 70 mg/kg (based on
ideal body weight at baseline) via a continuous 60 minute IV infusion within 24 hours
pre-operatively followed by a 30 mg/kg dose via a continuous 30 minute IV infusion on the
following days: within 24 hours post-transplantation, and on days 3, 10, 18, 28, then
monthly through 12 months post-transplantation. The enrollment will be staggered such that
early efficacy will be demonstrated in 5 patients prior to completing enrollment. Following
12 months of therapy, patients may be extended to receive additional monthly therapy.

Long-term follow up will occur through 30 months after the last dose of BG9588. Mechanistic
evaluations testing for allograft tolerance will be performed throughout the study including
evaluations for allospecific T cell deletion, allospecific T cell anergy, and alloantibody
production. The donor population for this study will include both living donors and
cadaveric donors. This is being done to address the theoretical concern that ischemic
reperfusion injury may negatively affect the efficacy of BG9588.