Safety & Efficacy Of Eculizumab In The Prevention Of AMR In Sensitized Recipients Of A Kidney Transplant From A Deceased Donor

An Open-Label, Single-Arm, Multicenter Trial to Determine Safety and Efficacy of Eculizumab in the Prevention of Antibody Mediated Rejection (AMR) in Sensitized Recipients of a Kidney Transplant From a Deceased Donor.

Primary Objective:

To evaluate the safety and potential efficacy of eculizumab to prevent AMR in sensitized recipients of deceased donor kidney transplants.

Study Overview

• Status: Completed
• Conditions: Stage V Chronic Kidney Disease
• Intervention / Treatment: Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
  • Camperdown, Australia, 2050
  • Parkville, Australia, 3050
• France
  • Bordeaux, France, 33076
  • Paris, France, 75743
  • Paris, France, 75010
  • Toulouse, France, 31059
  • Tours, France, 37044
• Italy
  • Brescia, Italy, 25123
  • Padova, Italy, 35128
• Spain
  • Barcelona, Spain, 08907
• Sweden
  • Gothenburg, Sweden, 413 45
  • Uppsala, Sweden, 751 85
• United Kingdom
  • Cambridge, United Kingdom, CB2 2QQ
  • London, United Kingdom, SE1 9RT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female participants ≥18 years old.
2. Participants with Stage V chronic kidney disease who received a kidney transplant from a deceased donor to whom they were sensitized.

3. History of prior exposure to HLA (human leukocyte antigen):

   • Prior solid organ or tissue allograft
   • Pregnancy
   • Blood transfusion
   • Prior exposure to specific donor's HLA

Exclusion Criteria:

1. Has received treatment with eculizumab at any time prior to enrolling in this study.
2. Blood type (A, B, and O blood glycoproteins-blood type) incompatible with deceased donor.
3. History of severe cardiac disease.
4. Prior splenectomy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Eculizumab; Eculizumab 1200 milligrams (mg) was administered intravenously (IV) over 25 to 45 minutes 1 hour prior to kidney allograft reperfusion. Eculizumab 900 mg was administered IV over 25 to 45 minutes on post-transplantation Days 1 and 7, and on post-transplantation Days 14, 21, and 28, plus or minus 2 days. Eculizumab 1200 mg was administered IV over 25 to 45 minutes on post-transplantation Days 35, 49, and 63, plus or minus 2 days.

Drug: Eculizumab; Other Names: Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation	Results are reported for post-transplantation treatment failure and composite endpoints, defined as the occurrence of biopsy-proven acute antibody-mediated rejection (AMR), graft loss, death, or loss to follow-up (including discontinuation) in the first 9 weeks post transplantation. The diagnosis of acute AMR (occurring within the first 9 weeks post transplantation) was based on kidney allograft dysfunction and a biopsy performed due to suspected rejection, proteinuria, increased serum creatinine, or acute tubular necrosis. Treatment failure was the occurrence of at least 1 of the composite endpoint components by Week 9 post transplantation. A participant experiencing multiple events was only counted once for the composite endpoint.	Baseline, Week 9

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12	Specific analyses of other AEs of interest that occurred at Month 12 included cumulative incidence of clinically significant infection (CSI); post-transplant lymphoproliferative disease (PTLD); malignancies; biopsy-proven acute cellular rejection (ACR) of any grade meeting Banff 2007 criteria; allograft loss for reasons other than AMR. CSIs were defined as infections (confirmed by culture, biopsy, genomic, or serologic findings) that required hospitalization or anti-infective treatment, or otherwise deemed significant by the Investigator. CSI subcategories of interest included cytomegalovirus (CMV) disease; BK virus disease; encapsulated bacterial infection; fungal infections; aspergillus infections. Results are reported as CIF, where a larger CIF indicates a higher incidence of an AE, and were calculated using Statistical Analysis System software and macro CIF. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.	Baseline, Month 12
Participants That Developed Severe ACR (Other AE Of Interest) At Month 12	This outcome measure focuses on the other AE of interest, severe ACR, which occurred at Month 12. It pertains specifically to the number of participants who developed severe ACR that did not respond to thymoglobulin or other lymphocyte-depleting agents. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.	Baseline, Month 12

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 29, 2012
• Primary Completion (ACTUAL): June 11, 2015
• Study Completion (ACTUAL): May 24, 2017

Study Registration Dates

• First Submitted: March 27, 2012
• First Submitted That Met QC Criteria: March 28, 2012
• First Posted (ESTIMATE): March 30, 2012

Study Record Updates

• Last Update Posted (ACTUAL): May 3, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: C10-002; 2010-019631-35 (EUDRACT_NUMBER)