An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome (aHUS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01193348
First received: August 31, 2010
Last updated: April 13, 2015
Last verified: April 2015
Results First Received: April 13, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Atypical Hemolytic-Uremic Syndrome
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
A total of 27 patients diagnosed with aHUS signed the informed consent and of these, 22 patients were treated. Five patients were excluded from the study due to failed screening procedure and did not receive eculizumab.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
At screening, patients had to have a platelet count < lower limit of normal range (<LLN) and serum creatinine level > 97 percentile for age; and had to exhibit signs or symptoms of hemolysis at the start of the current aHUS event with fragmented RBC and a negative Coombs test.

Reporting Groups
  Description
Eculizumab Eculizumab: Fixed dosing is based on body weight cohorts. Adjustment of dose to accommodate patient growth is possible.

Participant Flow for 4 periods

Period 1:   Screening Period
    Eculizumab  
STARTED     27  
COMPLETED     22  
NOT COMPLETED     5  
Screen Failure                 5  

Period 2:   Treatment Period (26 Weeks)
    Eculizumab  
STARTED     22  
COMPLETED     19  
NOT COMPLETED     3  
Positive Shiga-Toxin Result vial Local                 1  
Serious Adverse Event                 1  
Patient Requested to Withdraw                 1  

Period 3:   Extension Treatment Period
    Eculizumab  
STARTED     17  
COMPLETED     16  
NOT COMPLETED     1  
Physician Decision                 1  

Period 4:   Post Treatment Period (Patients Who Disc
    Eculizumab  
STARTED     10  
COMPLETED     8  
NOT COMPLETED     2  
Patient did not return for visit                 2  



  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.
The intent-to-treat (ITT) population was defined as all patients who received any amount of eculizumab, and were considered evaluable for safety and efficacy analyses. For both the efficacy and safety analyses, all 22 patients who were treated with study drug were included in the ITT population.

Reporting Groups
  Description
Eculizumab Eculizumab: Fixed dosing is based on body weight cohorts. Adjustment of dose to accommodate patient growth is possible.

Baseline Measures
    Eculizumab  
Number of Participants  
[units: participants]
  22  
Age  
[units: Years]
Mean (Standard Deviation)
  6.6  (6.06)  
Gender  
[units: participants]
 
Female     10  
Male     12  
Race (NIH/OMB)  
[units: participants]
 
American Indian or Alaska Native     0  
Asian     2  
Native Hawaiian or Other Pacific Islander     0  
Black or African American     0  
White     18  
More than one race     0  
Unknown or Not Reported     2  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Proportion of Patients With Complete TMA Response   [ Time Frame: Through 26 weeks ]

2.  Secondary:   Proportion of Patients With Complete Hematologic Response   [ Time Frame: Through 26 weeks ]

3.  Secondary:   Proportion of Patients With Platelet Count Normalization   [ Time Frame: Through 26 weeks ]

4.  Secondary:   Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement   [ Time Frame: Through 26 weeks ]

5.  Secondary:   Platelet Count Change From Baseline to 26 Weeks   [ Time Frame: Through 26 weeks ]

6.  Secondary:   Proportion of Patients With Complete TMA Response   [ Time Frame: Through End of Study, Median Exposure 55 Weeks ]

7.  Secondary:   Proportion of Patients With Complete Hematologic Response   [ Time Frame: Through End of Study, Median Exposure 55 Weeks ]

8.  Secondary:   Proportion of Patients With Platelet Count Normalization   [ Time Frame: Through End of Study, Median Exposure 55 Weeks ]

9.  Secondary:   Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement   [ Time Frame: Through End of Study, Median Exposure 55 Weeks ]

10.  Secondary:   Platelet Count Change From Baseline to 52 Weeks   [ Time Frame: Through 52 Weeks ]

11.  Secondary:   Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 5 - <10kg) N=3   [ Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort.Maintenance Phase was started 1 week after induction phase and dosing of eculizumab administration was every 2 weeks or every 3 weeks depending on patient weight cohort ]

12.  Secondary:   Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 10 - <20kg) N=7   [ Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort.Maintenance Phase was started 1 week after induction phase and dosing of eculizumab administration was every 2 weeks or every 3 weeks depending on patient weight cohort ]

13.  Secondary:   Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 20 - <30kg)   [ Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort ]

14.  Secondary:   Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 30 - <40kg) N=1   [ Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort ]

15.  Secondary:   Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort ≥40kg) N=5   [ Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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


No publications provided by Alexion Pharmaceuticals

Publications automatically indexed to this study:

Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01193348     History of Changes
Other Study ID Numbers: C10-003
Study First Received: August 31, 2010
Results First Received: April 13, 2015
Last Updated: April 13, 2015
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration