Eculizumab Therapy for Subclinical Antibody-mediated Rejection in Kidney Transplantation
Status:
Withdrawn
Trial end date:
2017-11-01
Target enrollment:
Participant gender:
Summary
Advances in renal transplantation have increased life-expectancy in patients with end-stage
kidney disease. Conventional immunosuppressive drugs prevent efficiently early allograft
losses due to T-cell mediated rejection. However, emerging data suggest that the majority of
late kidney failures may be attributable to antibody-mediated rejection (AMR), which poorly
responds to the currently available therapeutics. Complement-fixing donor-specific anti-HLA
antibodies are associated with the worst outcome in keeping with the well-established role of
the complement in AMR pathogenesis. Eculizumab, the first licenced complement blocker, has
been found efficient in reducing the occurrence of AMR lesions in highly sensitized patients.
A few reports also suggest that complement blockade may be of great value as salvage therapy
for graft-threatening severe AMR. However, no information is available in the literature
about the interest of complement blockade in curbing the progression of subclinical acute AMR
to chronic AMR.
The purpose of this study is to determine whether complement blockade with eculizumab is
effective and safe in the treatment of subclinical AMR in sensitized kidney transplant
recipients.
Despite appropriate therapies, up to 75% of patients having received a renal transplant with
preformed donor-specific antibody display subclinical AMR on their 3-month protocol biopsy.
Subclinical AMR is defined by histological lesions of AMR concomitant with stable graft
function. Moreover, the extent of these lesions at 3 month post-transplant correlates with
the occurrence of irreversible scars and chonic antibody-mediated rejection on the 12-month
biopsy.
This study aims to explore the efficacy and safety of eculizumab in patients exhibiting
subclinical AMR on their 3 month-post-transplant biopsy, to reduce or even normalize
microcirculation inflammation, and to prevent chronic rejection (transplant glomerulopathy)
on the 12 month-screening biopsy. Eculizumab-treated patients will be compared with
historical controls, matched for the lesions on the 3 month biopsy.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
Assistance Publique - Hôpitaux de Paris
Collaborators:
Alexion Pharmaceuticals Institut National de la Santé Et de la Recherche Médicale, France
Treatments:
Antibodies Complement System Proteins Eculizumab Immunoglobulins