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

NCT01106027 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 09-005627DD
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Kidney Transplant

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Acute Humoral Rejection (AHR) up to One Year Post Transplant.

  Diagnosis of AHR will be based histological findings using Banff '05 criteria.

  1 year posttransplant

Study Arms (1)

Eculizumab

EXPERIMENTAL

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 donor specific anti-donor human leukocyte antigen (HLA) antibody (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.

Drug: Eculizumab

Interventions

Eculizumab DRUG

Eculizumab 900 mg and 1200 mg, administered intravenously (IV)

Also known as: Soliris

Eculizumab

Eligibility Criteria

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

You may qualify if:

• years of age
• Has end stage renal disease (ESRD) and is to receive a kidney transplant from a deceased donor (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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Mayo Clinic: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55901, United States

Location

MeSH Terms

Interventions

eculizumab

Limitations and Caveats

The study was terminated early due to difficulty enrolling and competing industry-funded multi-center clinical trial.

Results Point of Contact

• Title: Dr. Mark Stegall
• Organization: Mayo Clinic

Stegall.Mark@mayo.edu

507-284-6275

Study Officials

• Mark Stegall, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 29, 2010
• First Posted: April 19, 2010
• Study Start: March 1, 2010
• Primary Completion: August 19, 2016
• Study Completion: August 19, 2016
• Last Updated: January 31, 2018
• Results First Posted: November 14, 2017

Record last verified: 2018-01

Locations

US (1)