WithdrawnPhase 1/2

Eculizumab Therapy for Subclinical Antibody-mediated Rejection in Kidney Transplantation

Stopped: disengagement of the sponsor Alexion Pharmaceuticals

0Started 2015-02

Plain-language 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.

Who can participate

Age range

18 Years – 75 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Male or female patients aged 18 -75 years. * Patients having received a kidney transplant from a living or deceased donor * Patients with stable renal function * Sensitized patient with at least one anti-HLA class II DSA (MFI \> 1000) within the first 3 months. * Adequate 3-month-protocol biopsy exhibiting microcirculation inflammation defined by glomerulitis Banff score (g) superior or egal 2 and /or peri-tubular capillaritis Banff score (ptc) superior or egal 2, AND the sum of scores g + ptc superior or egal 3. * C4d positive staining on 3-month-protocol biopsy * Adequate 3-month-protocol biopsy exhibiting limited scarred areas as defined as IF/TA score (ci + ct) inferior or egal 2 and no or minimal transplant glomerulopathy (cg inferior or egal 1) * Patients who have given written informed consent to participate in all aspects of the study. * Females of childbearing potential must have a negative pregnancy test within 48 hours prior to the first eculizumab administration. Exclusion Criteria: * Patients with known hypersensitivity to eculizumab or drugs with similar chemical structure. * Patients having experienced and having been treated for an acute antibody-mediated rejection within the first 3 months post-transplant * Patients with multi-organ transplant * Female patients who are pregnant, lactating or of child bearing potential and not practicing an approved method of birth control. * Patients with a known malignancy or history of malignancy ot…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Microcirculation inflammation

Timeframe: 12-month screening biopsies

Transplant glomerulopathy

Timeframe: 12 month screening biopsies

Microcirculation inflammation

Timeframe: 3 month screening biopsies

Transplant glomerulopathy

Timeframe: 3 month screening biopsies

Trial details

NCT IDNCT02113891

SponsorAssistance Publique - Hôpitaux de Paris

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2017-07

View on ClinicalTrials.gov More Subclinical Acute Antibody-mediated Rejection in Kidney Transplantation trials