A Multicenter Study of SBC-102 (Sebelipase Alfa) in Patients With Lysosomal Acid Lipase Deficiency/ ARISE (Acid Lipase Replacement Investigating Safety and Efficacy)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01757184
First received: December 17, 2012
Last updated: June 1, 2016
Last verified: June 2016
Results First Received: January 14, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Cholesterol Ester Storage Disease (CESD)
Lysosomal Acid Lipase Deficiency
Interventions: Drug: SBC-102 [sebelipase alfa] (1 mg/kg)
Drug: Placebo

  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 55 study centers located in 17 countries were initiated in this study including 49 during recruitment and 6 thereafter to allow transfer of subjects for local treatment. Subjects were screened at 41 of the 55 study centers in all countries except Greece.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
To assess eligibility, subjects were screened for a period of up to 6 weeks prior to enrollment in the study. A total of 86 subjects were screened. Six of these subjects underwent re-screening (of which 2 were eligible for the study). In total, 66 subjects were eligible for the study and 20 subjects were screen failures.

Reporting Groups
  Description
Double-blind SA, Followed by Open-Label SA Double-blind Period: IV infusions of sebelipase alfa (SA) at a dose of 1 mg/kg administered once every other week (qow); Open-Label Period: IV infusions of SA at a dose of 1 mg/kg administered qow. In the event of disease progression (based on protocol-defined criteria), subjects could be considered for a dose increase to 3 mg/kg qow during the open-label period.
Double-Blind Placebo Followed by Open-Label SA Double-blind Period: IV infusions of placebo administered once every other week (qow); Open-Label Period: IV infusions of sebelipase alfa (SA) at a dose of 1 mg/kg administered qow. In the event of disease progression (based on protocol-defined criteria), subjects could be considered for a dose increase to 3 mg/kg qow during the open-label period.

Participant Flow for 2 periods

Period 1:   Double-Blind Period
    Double-blind SA, Followed by Open-Label SA     Double-Blind Placebo Followed by Open-Label SA  
STARTED     36     30  
COMPLETED     35     30  
NOT COMPLETED     1     0  
Adverse Event                 1                 0  

Period 2:   Open-Label Period
    Double-blind SA, Followed by Open-Label SA     Double-Blind Placebo Followed by Open-Label SA  
STARTED     35     30  
COMPLETED     35 [1]   30 [1]
NOT COMPLETED     0     0  
[1] This period is currently ongoing.



  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.
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Reporting Groups
  Description
Double-Blind Sebelipase Alfa IV infusions of sebelipase alfa (SA) at a dose of 1 mg/kg administered once every other week (qow)
Double-Blind Placebo IV infusions of placebo administered once every other week (qow)
Total Total of all reporting groups

Baseline Measures
    Double-Blind Sebelipase Alfa     Double-Blind Placebo     Total  
Number of Participants  
[units: participants]
  36     30     66  
Age  
[units: participants]
     
<=18 years     23     24     47  
Between 18 and 65 years     13     6     19  
>=65 years     0     0     0  
Age  
[units: years]
Mean (Standard Deviation)
  16.9  (11.6)     15.2  (10.2)     16.1  (10.9)  
Gender  
[units: participants]
     
Female     18     15     33  
Male     18     15     33  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     6     4     10  
Not Hispanic or Latino     30     26     56  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     3     0     3  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     1     0     1  
White     27     28     55  
More than one race     0     0     0  
Unknown or Not Reported     5     2     7  
Region of Enrollment  
[units: participants]
     
Argentina     1     0     1  
Russian Federation     0     4     4  
United States     10     6     16  
Japan     2     0     2  
United Kingdom     3     1     4  
Spain     2     2     4  
Czech Republic     2     3     5  
Turkey     3     1     4  
Poland     4     3     7  
Italy     2     1     3  
Mexico     3     1     4  
Australia     2     2     4  
France     2     3     5  
Germany     0     2     2  
Croatia     0     1     1  



  Outcome Measures
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1.  Primary:   Percentage of Subjects Achieving Alanine Aminotransferase (ALT) Normalization   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]

2.  Secondary:   Percentage Change From Baseline in LDL-c   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]

3.  Secondary:   Percentage Change From Baseline in Non-HDL-c   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]

4.  Secondary:   Percentage of Subjects Achieving Aspartate Aminotransferase (AST) Normalization   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]

5.  Secondary:   Percentage Change From Baseline in Triglycerides   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]

6.  Secondary:   Percentage Change From Baseline in HDL-c   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]

7.  Secondary:   Percentage Change From Baseline in Liver Fat Content   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]

8.  Secondary:   Number of Subjects With Improvement in Liver Histology (Decrease of >5% in Hepatic Steatosis Score)   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]

9.  Secondary:   Percentage Change From Baseline in Liver Volume   [ Time Frame: Baseline to the end of the double-blind period (week 20) ]


  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 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: Mark Friedman, Medical Director
Organization: Alexion Pharmaceuticals
phone: 781-357-9953
e-mail: mark.friedman@alxn.com


Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01757184     History of Changes
Other Study ID Numbers: LAL-CL02
Study First Received: December 17, 2012
Results First Received: January 14, 2016
Last Updated: June 1, 2016
Health Authority: United States: Food and Drug Administration