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

NCT01919346 | Terminated Phase 2 DMC

• 1 other identifier: 13-0920
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

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

Keywords

Kidney Transplantation; Delayed Graft Function

Outcome Measures

Primary Outcomes (1)

• Hemodialysis

  The need of at least one dialysis treatment during the first 7 days after transplantation excluding: (i) requirement for a single dialysis session indicated for hyperkalemia (ii) hyperacute rejection, renal arterial and/or venous thrombosis, obstructive uropathy, recurrence of primary disease, and early thrombotic microangiopathy

  7 days post-transplantation

Secondary Outcomes (10)

• Estimated Glomerular Filtration Rate (GFR)

  6 months post-transplantation

• Hemodialysis

  8 weeks post-transplantation

• Primary Non-function

  8 weeks post-transplantation

• Graft Rejection

  6 months post-transplantation

• Patient Survival

  12 months post-transplantation

Study Arms (2)

Eculizumab

EXPERIMENTAL

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

Drug: Eculizumab

Normal Saline

PLACEBO COMPARATOR

Administered at same volume and time as Experimental arm

Drug: Normal Saline

Interventions

Eculizumab DRUG

Also known as: Soliris

Eculizumab

Normal Saline DRUG

Normal Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heeger, Peter, M.D.: lead
• Alexion Pharmaceuticals, Inc.: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (5)

Yale - New Haven Hospital

New Haven, Connecticut, 06540, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center

New York, New York, 10467, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Delayed Graft Function

Interventions

eculizumab; Saline Solution

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Peter S Heeger, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 9, 2013
• Study Start: August 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 27, 2018

Record last verified: 2018-02

Locations

US (5)