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

NCT ID: NCT01399593

Last Updated: 2017-10-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-02

Study Completion Date

2015-11-13

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Antibody Mediated Rejection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Eculizumab

Intervention Type DRUG

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Eculizumab

Intervention Type DRUG

Other Intervention Names

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Soliris

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Masayo Ogawa, MD

Role: STUDY_DIRECTOR

Alexion Pharmaceuticals, Inc.

Locations

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Birmingham, Alabama, United States

Site Status

La Jolla, California, United States

Site Status

Los Angeles, California, United States

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San Francisco, California, United States

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Washington D.C., District of Columbia, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Livingston, New Jersey, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Houston, Texas, United States

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North Terrace, South Australia, Australia

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Camperdown, , Australia

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Clayton VIC, , Australia

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Parkville VIC, , Australia

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Paris, , France

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Paris, , France

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Toulouse, , France

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Tours, , France

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Dresden, , Germany

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Heidelberg, , Germany

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Milan, , Italy

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Padua, , Italy

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Rotterdam, , Netherlands

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Oslo, , Norway

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Barcelona, , Spain

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Gothenburg, , Sweden

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Huddinge, , Sweden

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Uppsala, , Sweden

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London, England, United Kingdom

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London, England, United Kingdom

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Oxford, England, United Kingdom

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Birmingham, , United Kingdom

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Cambridge, , United Kingdom

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Coventry, , United Kingdom

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Countries

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United States Australia France Germany Italy Netherlands Norway Spain Sweden United Kingdom

References

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Marks WH, Mamode N, Montgomery RA, Stegall MD, Ratner LE, Cornell LD, Rowshani AT, Colvin RB, Dain B, Boice JA, Glotz D; C10-001 Study Group. Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial. Am J Transplant. 2019 Oct;19(10):2876-2888. doi: 10.1111/ajt.15364. Epub 2019 Apr 19.

Reference Type DERIVED
PMID: 30887675 (View on PubMed)

Other Identifiers

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2010-019630-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BB-IND: 100,003

Identifier Type: OTHER

Identifier Source: secondary_id

C10-001

Identifier Type: -

Identifier Source: org_study_id