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Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Crossmatch Deceased Donor Kidney Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Alexion Pharmaceuticals
Information provided by (Responsible Party):
Mark Stegall, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01106027
First received: March 29, 2010
Last updated: April 16, 2014
Last verified: April 2014

March 29, 2010
April 16, 2014
March 2010
December 2015   (final data collection date for primary outcome measure)
Number of subjects with acute humoral rejection (AHR) up to one year post transplant. [ Time Frame: 1 year posttransplant ] [ Designated as safety issue: No ]
Diagnosis of AHR will be based histological findings using Banff '05 criteria.
The primary objective of this study is the incidence of acute humoral rejection (AHR) in positive crossmatch deceased donor kidney transplant recipients to evaluate the safety and efficacy of eculizumab. [ Time Frame: Up to 15 months, including the 3 month follow-up period after the last dose of drug. ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01106027 on ClinicalTrials.gov Archive Site
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Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Crossmatch Deceased Donor Kidney Transplant
A Single Center, Open-label Study to Determine the Safety and Efficacy of a Dosing Regimen of Eculizumab Added to Conventional Treatment in the Prevention of Acute Humoral Rejection (AHR) in Positive Crossmatch Deceased Donor Kidney Transplantation (+XMatch DDKTx)

The purpose of this study is to test whether a dosing regimen of eculizumab in addition to standard posttransplant care in positive crossmatch deceased donor kidney transplant recipients will reduce the incidence of acute humoral rejection (AHR).

Patients included in this study will be those who have demonstrable anti-human leukocyte antigen (HLA) antibody specific for their deceased donor. It is our hypothesis that blockade of terminal complement activation with eculizumab at the time of transplant in combination with our current protocols will reduce the incidence of AHR in recipients of deceased donor kidney transplants who have anti-donor HLA antibody

A strongly positive crossmatch has long been considered an absolute contraindication to kidney transplantation and most patients with anti-HLA antibody never were able to receive a kidney transplant. Over the past decade, significant progress has been made in overcoming early antibody-mediated renal allograft injury. Despite our best efforts, transplantation in these patients is still complicated by a high rate of acute humoral rejection.

While we have successfully transplanted more than 250 patients with DSA using living donors, applying these protocols to recipients of deceased donors has been problematic. This primarily is due to the fact that in contrast to living donation, the timing of a deceased donor kidney transplant cannot be planned. This leads to inadequate time to perform the multiple pretransplant plasmapheresis treatments needed to achieve a safe level of DSA at transplant. Thus, there is a major unmet need to develop therapy that will allow for the successful transplantation of deceased donor kidneys in recipients who have DSA.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Kidney Transplant
Drug: Eculizumab
  • At the time of deceased donor kidney transplantation, patients will undergo one plasmapheresis prior to surgery.
  • Patients will be given 1200 mg of eculizumab intravenously over 30 minutes, 1 hour prior to surgery.
  • Patients will be given 900 mg of eculizumab on Day 1 post-transplant.
  • Patients will then be given 900 mg of eculizumab weekly through 4 weeks post-transplant
  • At week 4, patients will be assessed for DSA. Patients with total DSA normalized values <5000 will stop eculizumab treatment. Patients with total DSA normalized values >5000 will continue eculizumab treatment every 14 days from week 5 through week 9. The dose will be increased to 1200 mg and dosing will now be every 2 weeks instead of weekly. Similar "discontinuation assessments" will be performed at week 9, 26, 39 and 52.
Experimental: Eculizumab
Intervention: Drug: Eculizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
December 2015
December 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 18 years of age
  • Has end stage renal disease (ESRD) and is to receive a kidney transplant from a DD to whom he/she has a positive T or B cell crossmatch >200 at the time of transplant and DSA demonstrated by solid phase assays.
  • Willing to comply with the protocol
  • Females of child-bearing potential must have a negative pregnancy test (serum β-HCG) and sexually active females must agree to use a reliable and medically approved method of contraception
  • Willing and able to give written informed consent
  • Vaccinated against Neisseria meningitides (quadrivalent vaccine), Pneumococcus and H. influenzae at least two weeks prior to beginning desensitization

Exclusion Criteria:

  • Unstable cardiovascular condition
  • Previous splenectomy
  • Active bacterial or other infection which is clinically significant in the opinion of the investigator
  • Known or suspected hereditary complement deficiency
  • Participation in any other investigational drug study or was exposed to an investigational drug or device within 30 days of randomization
  • Pregnant, breast-feeding, or intending to conceive during the course of the study, including a one month follow-up period after drug discontinuation
  • Known hypersensitivity to the treatment drug or any of its excipients
  • History of illicit drug use or alcohol abuse within the previous year
  • History of meningococcal disease
  • Medical condition that, in the opinion of the investigator, might interfere with the patient's participation in the study, pose an added risk for the patient, or confound the assessment of the patient (e.g. severe cardiovascular or pulmonary disease)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01106027
09-005627DD
No
Mark Stegall, Mayo Clinic
Mayo Clinic
Alexion Pharmaceuticals
Principal Investigator: Mark Stegall, MD Mayo Clinic
Mayo Clinic
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP