Clinical trial NCT01399593: Safety & Efficacy of Eculizumab to Prevent AMR in Living Donor Kidney Transplant Recipients Requiring Desensitization
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Antibody Mediated Rejection
Keywords: Antibody Mediated Rejection
AMR
Acute Humoral Rejection
AHR
Living Donor
Kidney Transplant
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-07-22
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment Failure Rate
timeFrame: 9 weeks post-transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Washington, D.C.
country: United States
state: District of Columbia
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Livingston
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Houston
country: United States
state: Texas
city: North Terrace
country: Australia
state: South Australia
city: Camperdown
country: Australia
city: Clayton VIC
country: Australia
city: Parkville VIC
country: Australia
city: Paris
country: France
city: Paris
country: France
city: Toulouse Cedex
country: France
city: Tours Cedex
country: France
city: Dresden
country: Germany
city: Heidelberg
country: Germany
city: Milan
country: Italy
city: Padova
country: Italy
city: Rotterdam
country: Netherlands
city: Oslo
country: Norway
city: Barcelona
country: Spain
city: Göteborg
country: Sweden
city: Huddinge
country: Sweden
city: Uppsala
country: Sweden
city: London
country: United Kingdom
state: England
city: London
country: United Kingdom
state: England
city: Oxford
country: United Kingdom
state: England
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Coventry
country: United Kingdom
Study officials:
affiliation: Alexion Pharmaceuticals, Inc.
name: Masayo Ogawa, MD
role: STUDY_DIRECTOR
References:
citation: 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.