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

Alexion Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Antibody Mediated Rejection

Treatments: Drug: Eculizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01399593

C10-001

2010-019630-28 (EudraCT Number)

BB-IND: 100,003 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 102 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 2 patient groups

Eculizumab

Experimental group

Description:

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.

Treatment:

Drug: Eculizumab

Standard of Care

No Intervention group

Description:

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.