Overview

This trial is active, not recruiting.

Condition kidney transplant
Treatment eculizumab
Target C5
Sponsor Mark Stegall
Collaborator Alexion Pharmaceuticals
Start date March 2008
End date May 2017
Trial size 20 participants
Trial identifier NCT00670774, 07-007208

Summary

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. Our group has performed more than 200 such transplants providing the possibility of transplant to previously untransplantable patients. Despite our best efforts, transplantation in these patients is still complicated by a high rate of acute humoral rejection.

Patients included in this study will be those who have demonstrable anti-HLA antibody specific for their living donor. It is our hypothesis that blockade of terminal complement activation at the time of transplant in combination with our current protocols will reduce the incidence of AHR in patients with anti-donor HLA antibody.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
eculizumab Soliris
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 B cell FCXM. Patients with B cell FCXM less than 200 will stop eculizumab treatment. Patients with B cell FXCM greater than or equal to 200 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. In addition, eculizumab 600 mg will be administered immediately after each plasmapheresis (PP) and immediately after any fresh frozen plasma (FFP) that is given post-transplant during the treatment period

Primary Outcomes

Measure
The primary objective of this study is to evaluate the safety and efficacy of eculizumab in preventing AMR in positive crossmatch patients undergoing +XMatch LDKTx.
time frame: 6 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - 18 years of age - Has end stage renal disease (ESRD) and is to receive a kidney transplant from a LD to whom he/she has either: - a positive crossmatch requiring pretransplant desensitization (defined as a positive T-cell FCXM of greater than or equal to 300 but less than 450 prior to desensitization, or as a positive B-cell FCXM of > 300 but < 450 prior to desensitization with demonstrable Class II DSA on solid-phase assays). Subsequent to desensitization, patient must have, at the time of transplant, a T-cell and B-cell FCXM less than 300; or - a positive crossmatch not requiring desensitization (defined as FCXM between 200 and 299) - 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 or 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 the two 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) - Previously been enrolled in this trial

Additional Information

Official title 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 Antibody-mediated Rejection (AMR) in Positive Crossmatch Living Donor Kidney Transplantation
Principal investigator Mark D. Stegall, M.D.
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by Mayo Clinic.