MedTrace Logo

Eculizumab Therapy for Subclinical Antibody-mediated Rejection in Kidney Transplantation

NCT02113891 · Status: WITHDRAWN · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL

Last updated 2025-11-20

No results posted yet for this study

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.

Conditions

  • Subclinical Acute Antibody-mediated Rejection in Kidney Transplantation

Interventions

DRUG

Eculizumab

Eculizumab induction: 900 mg IV every 7 days for 4 doses, a fifth 1200 mg dose 7 days later Eculizumab maintenance: 15 1200 mg doses every 14 days. (each patient will receive a total of 20 eculizumab doses during the whole treatment period from 3 month to 12 month post-transplant).

Sponsors & Collaborators

  • Institut National de la Santé Et de la Recherche Médicale, France

    collaborator OTHER_GOV

  • Alexion Pharmaceuticals, Inc.

    collaborator INDUSTRY

  • URC-CIC Paris Descartes Necker Cochin

    collaborator OTHER

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Principal Investigators

  • Christophe LEGENDRE, MD · Service de Transplantation Rénale, Hôpital Necker Université Paris Descartes 149 rue de Sèvres 75015 Paris, France

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2015-02-28
Primary Completion
2017-07-31
Completion
2017-11-30

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02113891 on ClinicalTrials.gov