Safety & Efficacy of Eculizumab to Prevent AMR in Living Donor Kidney Transplant Recipients Requiring Desensitization

September 4, 2017 updated by: Alexion Pharmaceuticals

A Randomized, Open-label, Multicenter Trial to Determine Safety and Efficacy of Eculizumab in the Prevention of Antibody Mediated Rejection (AMR) in Living Donor Kidney Transplant Recipients Requiring Desensitization Therapy

The purpose of this trial was to determine the safety and efficacy of eculizumab in the prevention of antibody-mediated rejection (AMR) in sensitized recipients of a living donor kidney transplant requiring desensitization therapy.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The main objective of this study was to evaluate the safety and efficacy of eculizumab to prevent AMR in sensitized recipients of living donor kidney transplants requiring desensitization therapy prior to transplantation. The primary endpoint focused on acute AMR during the first 9 weeks post-transplantation.

Patients were to be vaccinated against N. meningitidis at least 14 days prior to study drug initiation and revaccinated 30 days later. If not vaccinated 14 days prior, prophylactic antibiotics were to be administered. Pre-transplant infectious disease assessment was to be performed as part of the screening assessment.

Patients were to undergo desensitization therapy according to the practice of the local transplant center prior to transplantation, and this desensitization practice was to be uniformly applied for all patients at that center throughout the study. The actual length of desensitization for an individual patient was based on the clinical judgment of the Transplant Center team. Rituximab was prohibited in all patients as part of the pre-transplantation desensitization therapy due to potential pharmacodynamic interactions.

The control group was designed to test eculizumab against the best available care (referred to as standard of care, or SOC) consisting of plasmapheresis (PP) and/or intravenous immunoglobulin (IVIg). The best available care consisting of PP and IVIg was chosen because these modalities combined represented the most prevalent therapy reported in the literature and were the best available therapies at the time of this protocol's inception as per the transplant community.

Study Type

Interventional

Enrollment (Actual)

102

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Camperdown, Australia, 2050
      • Clayton VIC, Australia, 3168
      • Parkville VIC, Australia, 3050
    • South Australia
      • North Terrace, South Australia, Australia, 5000
  • France
      • Paris, France, 75743
      • Paris, France, 75010
      • Toulouse Cedex, France, 31059
      • Tours Cedex, France, 37044
  • Germany
      • Dresden, Germany, 01307
      • Heidelberg, Germany, 69120
  • Italy
      • Milan, Italy, 20162
      • Padova, Italy, 35128
  • Netherlands
      • Rotterdam, Netherlands, 3015 CE
  • Norway
      • Oslo, Norway, N-0027
  • Spain
      • Barcelona, Spain, 8036
  • Sweden
      • Göteborg, Sweden, 413 45
      • Huddinge, Sweden, SE 141 86
      • Uppsala, Sweden, S 751 85
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
      • Cambridge, United Kingdom, CB2 2QQ
      • Coventry, United Kingdom, CV2 2DX
    • England
      • London, England, United Kingdom, SE1 9RT
      • London, England, United Kingdom, W12 0HS
      • Oxford, England, United Kingdom, OX3 7LJ
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
    • California
      • La Jolla, California, United States, 92037
      • Los Angeles, California, United States, 90095
      • San Francisco, California, United States, 94143
    • District of Columbia
      • Washington, D.C., District of Columbia, United States, 20007
    • Georgia
      • Atlanta, Georgia, United States, 30309
    • Illinois
      • Chicago, Illinois, United States, 60612
    • Maryland
      • Baltimore, Maryland, United States, 21205
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Minnesota
      • Rochester, Minnesota, United States, 55905
    • Missouri
      • Saint Louis, Missouri, United States, 63110
    • New Jersey
      • Livingston, New Jersey, United States, 07039
    • New York
      • New York, New York, United States, 10032
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
    • Ohio
      • Cincinnati, Ohio, United States, 45267
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
    • Texas
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients ≥18 years old
  2. Patients with Stage IV or Stage V chronic kidney disease who will receive a kidney transplant from a living donor to whom they are sensitized and require desensitization prior to transplantation

Exclusion Criteria:

  1. ABO incompatible with living donor
  2. Any medical condition that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confounds the assessment of the patient

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eculizumab
Patients were to receive eculizumab 1200 mg prior to allograft transplantation (Day 0, starting approximately one hour prior to kidney allograft reperfusion), eculizumab 900 mg (Days 1, 7, 14, 21, and 28), and eculizumab 1200 mg (Weeks 5, 7 and 9). All doses of eculizumab were administered intravenously: the median infusion time was 39 minutes.
Drug: Eculizumab
Other Names:
  • Soliris
No Intervention: Standard of Care
Patients received standard of care (SOC) prophylactic therapy for acute AMR according to the SOC choice at each participating investigative site, which could have included any combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg). Patients randomized to SOC who were diagnosed with AMR could have received eculizumab for the treatment of AMR after initially receiving PP and/or IVIg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Failure Rate
Time Frame: 9 weeks post-transplantation
The primary efficacy variable was a binary outcome variable where patients meeting the composite endpoint of the occurrence of 1) biopsy-proven acute AMR, 2) graft loss, 3) patient death, or 4) loss to follow-up definition at Week 9 post-transplantation were considered treatment failures and all others were considered treatment successes.
9 weeks post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals

Investigators

  • Study Director: Masayo Ogawa, MD, Alexion Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 2, 2011

Primary Completion (Actual)

May 13, 2014

Study Completion (Actual)

November 13, 2015

Study Registration Dates

First Submitted

July 19, 2011

First Submitted That Met QC Criteria

July 20, 2011

First Posted (Estimate)

July 22, 2011

Study Record Updates

Last Update Posted (Actual)

October 3, 2017

Last Update Submitted That Met QC Criteria

September 4, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C10-001
  • 2010-019630-28 (EudraCT Number)
  • BB-IND: 100,003 (Other Identifier: FDA IND: 100,003)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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