Eculizumab for Prevention of Delayed Graft Function (DGF) in Kidney Transplantation

NCT ID: NCT01919346

Last Updated: 2018-02-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2017-12-31

Brief Summary

The purpose of this study is to evaluate the efficacy of Eculizumab in the prevention of Delayed Graft Function following deceased donor kidney transplantation. Based on experimental data and supportive observations in humans associating complement gene upregulation with ischemic reperfusion (IR) injury, it is hypothesized that C5 cleavage is a key step in the pathogenesis of ischemic reperfusion injury following transplantation. It is further hypothesized that Eculizumab, a humanized monoclonal antibody that blocks C5 cleavage in humans will be an effective prophylactic agent to prevent IR injury in high risk recipients. This trial is a prospective, randomized study to test the efficacy of eculizumab vs. placebo given once at the time of transplantation and once again 24 hours later in preventing delayed graft function in first adult recipients of deceased donor kidneys.

Conditions

Delayed Graft Function; Kidney Transplantation; Complement Activity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Eculizumab

Eculizumab 1200 mg (diluted in Sodium Chloride (NaCl) to 5mg/mL, volume = 240 mL) will be given intraoperatively at the time of transplantation prior to reperfusion of the renal allograft and again at 900 mg (diluted in NaCl to 5mg/mL, volume = 180 mL) 12-24 hours post-transplantation

Group Type: EXPERIMENTAL

Eculizumab

Intervention Type: DRUG

Normal Saline

Administered at same volume and time as Experimental arm

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

Interventions

Eculizumab

Intervention Type: DRUG

Normal Saline

Intervention Type: DRUG

Other Intervention Names

Soliris

Eligibility Criteria

Inclusion Criteria

• Age 18 years or older
• Weight > 40 kg
• Male or Female
• Recipient of first deceased donor kidney
• Able to provide written informed consent
• Transplant candidate as per site specific guidelines
• Dialysis dependent renal failure (initiated more than 2 months prior to transplant)
• Recipients of kidneys defined as:

1. Extended Criteria Donor (ECD) kidney with brain death: Kidney donors 60 years of age or older; or donors aged 50-59 years and have two of the following features: Hypertension, terminal serum creatinine > 1.5 mg/dL, or death from cerebrovascular accident (CVA), OR

2. Standard Criteria Donor (SCD) kidney with actual cold ischemia time (CIT) 18 - 40 hours

Exclusion Criteria

• Patient is planned to receive a multi-organ transplant
• Kidney from donor < 6 years of age
• Dual kidney transplant (from same donor, including en bloc)
• Living donor kidney transplant
• Recipients with donor-specific anti-HLA antibodies of more than 3,000 MFI
• Participation in another investigational drug study
• Recipient BMI > 40
• ABO incompatible
• DCD (donor with cardiac death) Donor
• Women who are pregnant or breast-feeding
• Women of child bearing potential who are unable or unwilling to use a medically acceptable form of contraception (defined as the use of oral, injected or implanted hormonal methods of contraception, intrauterine device (IUD)or intrauterine system (IUS), barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository)
• Patients with HBsAg-positive status, HCV infection, or HIV infection
• Patients with atypical hemolytic uremic syndrome (aHUS) or C3 glomerulonephritis (C3GN)
• Active bacterial or other infection which is clinically significant in the opinion of the investigator
• Patients with history of splenectomy
• Patients with history of meningococcal disease
• Patients allergic to or unable to tolerate Ciprofloxacin
• Patients unable or unwilling to receive vaccination against meningitis prior to study drug administration
• Patients with a known or suspected hereditary complement deficiency
• Patients with a history of cancer (other than non melanoma skin cancers) within the last five years
• Donors of more than 70 years of age
• Subjects with a psychiatric or physical illness which in the opinion of the Investigator would interfere with their ability to participate in the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

Heeger, Peter, M.D.

INDIV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter S Heeger, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Yale - New Haven Hospital

New Haven, Connecticut, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Montefiore Medical Center

New York, New York, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

13-0920

Identifier Type: -

Identifier Source: org_study_id