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Safety & Efficacy of Eculizumab to Prevent AMR in Living Donor Kidney Transplant Recipients Requiring Desensitization

This study has been terminated.
(Did not achieve statistical significance for primary endpoint)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01399593
First Posted: July 22, 2011
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Alexion Pharmaceuticals
Results First Submitted: March 9, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Antibody Mediated Rejection
Intervention: Drug: Eculizumab

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment period lasted from Nov 2011 to Mar 2014. Forty-one sites in Australia, the European Union, and North America participated in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Written consent was provided prior to performing any study-required assessments (N = 275). Patients who passed screening (N = 137) underwent desensitization therapy according to local transplant center practice prior to transplantation. A total of 104 patients were randomized; of these, 102 were transplanted and received eculizumab or SOC.

Reporting Groups
  Description
Eculizumab Patients were to receive eculizumab 1200 mg prior to allograft transplantation (Day 0, starting approximately one hour prior to kidney allograft reperfusion), eculizumab 900 mg (Days 1, 7, 14, 21, and 28), and eculizumab 1200 mg (Weeks 5, 7 and 9).
Standard of Care Patients received standard of care (SOC) prophylactic therapy for acute AMR according to the SOC choice at each participating investigative site, which could have included any combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg). Patients randomized to SOC who were diagnosed with AMR could have received eculizumab for the treatment of AMR after initially receiving PP and/or IVIg.

Participant Flow:   Overall Study
    Eculizumab   Standard of Care
STARTED   51   51 
COMPLETED   48   49 
NOT COMPLETED   3   2 
Physician Decision                1                0 
Adverse Event                1                0 
Death                1                1 
Transplantectomy                0                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Eculizumab

Patients in the eculizumab treatment group were to receive eculizumab for 9 weeks according to the following dosing regimen:

Eculizumab 1200 mg prior to allograft transplantation (Day 0, starting approximately one hour prior to kidney allograft reperfusion), eculizumab 900 mg (Days 1, 7, 14, 21, and 28), and eculizumab 1200 mg (Weeks 5, 7 and 9). All doses of eculizumab were administered intravenously.

Standard of Care (SOC) Patients in the standard of care (SOC) treatment group received prophylactic therapy for acute AMR according to the SOC choice at each participating investigative site, which could have included any combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg). Patients randomized to SOC who were diagnosed with AMR could have received eculizumab for the treatment of AMR after initially receiving PP and/or IVIg.
Total Total of all reporting groups

Baseline Measures
   Eculizumab   Standard of Care (SOC)   Total 
Overall Participants Analyzed 
[Units: Participants]
 51   51   102 
Age, Customized 
[Units: Participants]
Count of Participants
     
In utero       
Participants Analyzed 
[Units: Participants]
 51   51   102 
In utero   0   0   0 
Preterm newborn - gestational age < 37 wk       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Preterm newborn - gestational age < 37 wk   0   0   0 
Newborns (0-27 days)       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Newborns (0-27 days)   0   0   0 
Infants and toddlers (28 days-23 months)       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Infants and toddlers (28 days-23 months)   0   0   0 
Children (2-11 years)       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Children (2-11 years)   0   0   0 
Adolescents (12-17 years)       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Adolescents (12-17 years)   0   0   0 
Adults (18-64 years)       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Adults (18-64 years)   47   49   96 
From 65 to 84 years       
Participants Analyzed 
[Units: Participants]
 51   51   102 
From 65 to 84 years   4   2   6 
85 years and over       
Participants Analyzed 
[Units: Participants]
 51   51   102 
85 years and over   0   0   0 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 51   51   102 
Female      37  72.5%      30  58.8%      67  65.7% 
Male      14  27.5%      21  41.2%      35  34.3% 
Race (NIH/OMB) [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 51   51   102 
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0% 
Asian      2   3.9%      3   5.9%      5   4.9% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      6  11.8%      6  11.8%      12  11.8% 
White      37  72.5%      36  70.6%      73  71.6% 
More than one race      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      6  11.8%      6  11.8%      12  11.8% 
[1] Patients appearing under "Unknown or Not Reported" were categorized as "Other" by the investigator.
Region of Enrollment 
[Units: Participants]
Count of Participants
     
Australia       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Australia   4   1   5 
France       
Participants Analyzed 
[Units: Participants]
 51   51   102 
France   3   7   10 
Germany       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Germany   1   1   2 
Italy       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Italy   2   4   6 
Netherlands       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Netherlands   0   3   3 
Norway       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Norway   1   1   2 
Spain       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Spain   3   4   7 
Sweden       
Participants Analyzed 
[Units: Participants]
 51   51   102 
Sweden   1   4   5 
United Kingdom       
Participants Analyzed 
[Units: Participants]
 51   51   102 
United Kingdom   10   5   15 
United States       
Participants Analyzed 
[Units: Participants]
 51   51   102 
United States   26   21   47 
Total Donor-Specific Antibodies (DSA) [1] [2] 
[Units: Mean fluorescence intensity (MFI)]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 50   48   98 
   15394.7  (14163.78)   17469.8  (12573.44)   16411.1  (13380.16) 
[1] The presence of donor-specific antibodies (DSA) indicates that a patient has become sensitized, i.e., has preformed antibodies against donor specific human leukocyte antigens (HLAs). A higher DSA level indicates greater sensitization and greater risk of antibody-mediated rejection (AMR).
[2] Data unavailable for 4 subjects.
Highest Single Donor-Specific Antibodies (DSA) [1] [2] 
[Units: Mean fluorescence intensity (MFI)]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 50   48   98 
   8135  (4048.08)   8740.7  (4289.97)   8431.7  (4157.87) 
[1] The presence of donor-specific antibodies (DSA) indicates that a patient has become sensitized, i.e., has preformed antibodies against donor specific human leukocyte antigens (HLAs). A higher DSA level indicates greater sensitization and greater risk of antibody-mediated rejection (AMR).
[2] Data unavailable for 4 subjects.


  Outcome Measures

1.  Primary:   Treatment Failure Rate   [ Time Frame: 9 weeks post-transplantation ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Data interpretation confounded by open-label study with potential reporting bias, unequal exposure to randomized prevention therapy between groups, some patients in SOC arm received eculizumab for treatment of AMR, all patients immunosuppressed.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Alexion Pharmaceuticals, Inc.
Organization: Alexion Pharmaceuticals, Inc.
e-mail: clinicaltrials@alexion.com



Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01399593     History of Changes
Other Study ID Numbers: C10-001
2010-019630-28 ( EudraCT Number )
BB-IND: 100,003 ( Other Identifier: FDA IND: 100,003 )
First Submitted: July 19, 2011
First Posted: July 22, 2011
Results First Submitted: March 9, 2017
Results First Posted: April 19, 2017
Last Update Posted: October 3, 2017