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

• ClinicalTrials.gov Identifier: NCT01919346
• Recruitment Status: Terminated
• First Posted: August 9, 2013
• Last Update Posted: February 27, 2018
• Sponsor: Heeger, Peter, M.D.
• Collaborators: Alexion Pharmaceuticals; Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Heeger, Peter, M.D.

Tracking Information

• First Submitted Date: August 7, 2013
• First Posted Date: August 9, 2013
• Last Update Posted Date: February 27, 2018
• Study Start Date: August 2013
• Actual Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 7, 2013)

Hemodialysis [ Time Frame: 7 days post-transplantation ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 11, 2014)

• Estimated Glomerular Filtration Rate (GFR) [ Time Frame: 6 months post-transplantation ]
  Estimated GFR as determined from the 4-variable MDRD (Modified Diet in Renal Disease) equation on days 7, 30, 90 and 180 post-transplantation
• Hemodialysis [ Time Frame: 8 weeks post-transplantation ]
  Number of dialysis sessions at 30 days and 8 weeks post-transplantation
• Primary Non-function [ Time Frame: 8 weeks post-transplantation ]
  The incidence of primary non-function (PNF) defined as the need for dialysis-dependency for more than 8 weeks
• Graft Rejection [ Time Frame: 6 months post-transplantation ]
  Incidence of graft rejection within 6 months
• Patient Survival [ Time Frame: 12 months post-transplantation ]
  Patient survival at 12 months post-transplantation
• Graft Survival [ Time Frame: 12 months post-transplantation ]
  Death censored graft survival at 12 months post-transplantation
• Serum Creatinine [ Time Frame: 3 days post-transplantation ]
  Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation
• Urine Output [ Time Frame: 3 days post-transplantation ]
  Percentage of patients with total 24-hour urine output of more than 500 mL on post-transplantation days 2 and 3
• Biomarkers [ Time Frame: 6 months post-transplantation ]
  Absolute levels of biomarkers associated with acute renal injury
• Qualified Delayed Graft Function (qDGF) [ Time Frame: 7 days post-transplantation ]
  The incidence of qDGF defined as the requirement for dialysis for any reason in the first 7 days post-transplantation

Original Secondary Outcome Measures (submitted: August 7, 2013)

• Estimated Glomerular Filtration Rate (GFR) [ Time Frame: 6 months post-transplantation ]
  Estimated GFR as determined from the 4-variable MDRD (Modified Diet in Renal Disease) equation on days 7, 30, 90 and 180 post-transplantation
• Hemodialysis [ Time Frame: 8 weeks post-transplantation ]
  Number of dialysis sessions in the 8 weeks post-transplantation period
• Primary Non-function [ Time Frame: 8 weeks post-transplantation ]
  The incidence of primary non-function (PNF) defined as the need for dialysis-dependency for more than 8 weeks
• Graft Rejection [ Time Frame: 6 months post-transplantation ]
  Incidence of graft rejection within 6 months
• Patient Survival [ Time Frame: 12 months post-transplantation ]
  Patient survival at 12 months post-transplantation
• Graft Survival [ Time Frame: 12 months post-transplantation ]
  Death censored graft survival at 12 months post-transplantation
• Serum Creatinine [ Time Frame: 3 days post-transplantation ]
  Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation
• Urine Output [ Time Frame: 3 days post-transplantation ]
  Percentage of patients with total 24-hour urine output of more than 500 mL on post-transplantation days 2 and 3
• Biomarkers [ Time Frame: 6 months post-transplantation ]
  Absolute levels of biomarkers (Ngal, Kim-1, IL-18) associated with acute renal injury

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Eculizumab for Prevention of Delayed Graft Function (DGF) in Kidney Transplantation
• Official Title: Eculizumab for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplantation
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Delayed Graft Function
• Kidney Transplantation
• Complement Activity

Intervention

• Drug: Eculizumab
  Other Name: Soliris
• Drug: Normal Saline

Study Arms

• Experimental: 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
  Intervention: Drug: Eculizumab
• Placebo Comparator: Normal Saline
  Administered at same volume and time as Experimental arm
  Intervention: Drug: Normal Saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 23, 2018): 21
• Original Estimated Enrollment (submitted: August 7, 2013): 24
• Actual Study Completion Date: December 2017
• Actual Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01919346
• Other Study ID Numbers: 13-0920
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Heeger, Peter, M.D.
• Study Sponsor: Heeger, Peter, M.D.

Collaborators

• Alexion Pharmaceuticals
• Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Peter S Heeger, MD; Icahn School of Medicine at Mount Sinai

• PRS Account: Heeger, Peter, M.D.
• Verification Date: February 2018