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Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency

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ClinicalTrials.gov Identifier: NCT01488097
Recruitment Status : Completed
First Posted : December 8, 2011
Results First Posted : May 9, 2016
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cholesterol Ester Storage Disease (CESD)
Lysosomal Acid Lipase Deficiency
LAL-Deficiency
Intervention Drug: sebelipase alfa
Enrollment 8
Recruitment Details  
Pre-assignment Details 9 participants who completed Study LAL-CL01 (received all 4 doses of sebelipase alfa) were screened for eligibility for enrollment in this extension study (LAL-CL04). 8 participants met all enrollment criteria and were enrolled. 1 participant who required a liver transplant no longer met the entry criteria.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description Participants were administered sebelipase alfa once weekly (qw) as an intravenous (IV) infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 milligrams per kilogram [mg/kg]) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing every other week (qow) at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Period Title: Overall Study
Started 8
Received Study Drug in Extension Study 8
Completed 7
Not Completed 1
Reason Not Completed
Lost to Follow-up             1
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Baseline Participants 8
Hide Baseline Analysis Population Description
All participants who received any amount of study drug in the extension study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
<=18 years
0
   0.0%
Between 18 and 65 years
8
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants
30.3  (10.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
Female
2
  25.0%
Male
6
  75.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
8
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
8
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
Canada
1
  12.5%
Czechia
1
  12.5%
United States
3
  37.5%
United Kingdom
2
  25.0%
France
1
  12.5%
1.Primary Outcome
Title Number Of Participants Reporting TEAEs And IARs
Hide Description Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-associated reactions (IARs). The number of participants who discontinued from the study due to a TEAE is also presented. An IAR was defined as any adverse event that occurred during the 2-hour infusion or within 4 hours after the end of the infusion and was assessed by the investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. TEAEs that occurred after the first dose administration at Week 1 through the End of Study (EOS) are presented. End of study was 30 days (+ 7 days) after the last dose of study drug (at Week 260).
Time Frame From after first dose administration post-Baseline through EOS during study LAL-CL04
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: All participants who received any amount of study drug in the extension study.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Participants Analyzed 8
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
8
 100.0%
Serious TEAEs
1
  12.5%
IARs
2
  25.0%
TEAEs Leading to Study Discontinuation
0
   0.0%
2.Secondary Outcome
Title Changes From Baseline In ALT And AST
Hide Description Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time Frame Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (FAS) for whom ALT and AST data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: units (U)/liter (L)
ALT Week 12 Number Analyzed 8 participants
-35.9  (19.99)
ALT Week 24 Number Analyzed 8 participants
-38.1  (24.00)
ALT Week 52 Number Analyzed 7 participants
-40.6  (20.50)
ALT Week 104 Number Analyzed 8 participants
-42.5  (19.65)
ALT Week 156 Number Analyzed 8 participants
-29.5  (20.38)
ALT Week 208 Number Analyzed 7 participants
-26.7  (30.58)
ALT Week 260 Number Analyzed 5 participants
-31.6  (21.78)
ALT EOS Number Analyzed 7 participants
-26.6  (31.10)
AST Week 12 Number Analyzed 8 participants
-13.9  (7.02)
AST Week 24 Number Analyzed 8 participants
-12.4  (11.71)
AST Week 52 Number Analyzed 7 participants
-18.6  (12.82)
AST Week 104 Number Analyzed 8 participants
-11.8  (15.59)
AST Week 156 Number Analyzed 8 participants
-12.8  (9.95)
AST Week 208 Number Analyzed 7 participants
-10.4  (14.86)
AST Week 260 Number Analyzed 5 participants
-10.8  (13.70)
AST EOS Number Analyzed 7 participants
-15.3  (14.27)
3.Secondary Outcome
Title Changes From Baseline In Liver Volume
Hide Description Changes in liver volume from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS was assessed by magnetic resonance imaging (MRI). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04. Liver volume was expressed as multiples of normal (MN), where normal is defined as 2.5% of body weight.
Time Frame Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the FAS for whom liver volume data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: Multiples of Normal (MN)
Week 10 or 12 Number Analyzed 8 participants
-0.096  (0.0892)
Week 24 Number Analyzed 8 participants
-0.099  (0.1513)
Week 52 Number Analyzed 7 participants
-0.096  (0.0641)
Week 104 Number Analyzed 7 participants
-0.176  (0.0801)
Week 156 Number Analyzed 5 participants
-0.082  (0.0732)
Week 208 Number Analyzed 5 participants
-0.182  (0.0556)
Week 260 Number Analyzed 2 participants
-0.218  (0.0388)
EOS Number Analyzed 2 participants
-0.205  (0.0358)
4.Secondary Outcome
Title Changes From Baseline In Liver Fat Content
Hide Description Changes in liver fat content from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260, as assessed by multi-echo gradient-echo MRI. Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time Frame Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the FAS for whom liver fat content data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: percentage fat fraction
Week 10 or 12 Number Analyzed 5 participants
-2.816  (1.8025)
Week 24 Number Analyzed 5 participants
-2.772  (3.0024)
Week 52 Number Analyzed 4 participants
-3.633  (2.5736)
Week 104 Number Analyzed 4 participants
-4.348  (2.4486)
Week 156 Number Analyzed 4 participants
-3.953  (4.1182)
Week 208 Number Analyzed 3 participants
-4.007  (3.4260)
Week 260 Number Analyzed 2 participants
-0.060  (3.4507)
5.Secondary Outcome
Title Changes From Baseline In GGT And ALP
Hide Description Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for gamma glutamyltransferase (GGT) and alkaline phosphatase (ALP). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time Frame Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the FAS for whom GGT and ALP data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: U/L
GGT Week 12 Number Analyzed 8 participants
-13.6  (28.79)
GGT Week 24 Number Analyzed 8 participants
-13.8  (24.63)
GGT Week 52 Number Analyzed 7 participants
-14.0  (18.89)
GGT Week 104 Number Analyzed 8 participants
-22.4  (34.01)
GGT Week 156 Number Analyzed 8 participants
0.1  (11.32)
GGT Week 208 Number Analyzed 7 participants
2.3  (10.13)
GGT Week 260 Number Analyzed 5 participants
-6.0  (12.33)
GGT EOS Number Analyzed 7 participants
-4.0  (7.70)
ALP Week 12 Number Analyzed 8 participants
-15.3  (12.09)
ALP Week 24 Number Analyzed 8 participants
-18.3  (20.74)
ALP Week 52 Number Analyzed 7 participants
-12.4  (18.78)
ALP Week 104 Number Analyzed 8 participants
-18.0  (9.68)
ALP Week 156 Number Analyzed 8 participants
-6.4  (11.81)
ALP Week 208 Number Analyzed 7 participants
-5.9  (16.60)
ALP Week 260 Number Analyzed 5 participants
-14.2  (21.32)
ALP EOS Number Analyzed 7 participants
-7.9  (20.82)
6.Secondary Outcome
Title Changes From Baseline In Serum Lipids
Hide Description Lipid changes from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS were measured in serum for total cholesterol (Total-C), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time Frame Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the FAS for whom lipid data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: mg/dL
Total-C Week 12 Number Analyzed 8 participants
-34.5  (40.50)
Total-C Week 24 Number Analyzed 8 participants
-59.3  (38.83)
Total-C Week 52 Number Analyzed 7 participants
-73.9  (54.43)
Total-C Week 104 Number Analyzed 8 participants
-60.8  (50.82)
Total-C Week 156 Number Analyzed 8 participants
-36.4  (43.90)
Total-C Week 208 Number Analyzed 7 participants
1.1  (93.21)
Total-C Week 260 Number Analyzed 5 participants
-45.5  (50.85)
Total-C EOS Number Analyzed 7 participants
-21.9  (59.89)
HDL-C Week 12 Number Analyzed 8 participants
4.9  (3.95)
HDL-C Week 24 Number Analyzed 8 participants
5.7  (6.19)
HDL-C Week 52 Number Analyzed 7 participants
9.0  (7.25)
HDL-C Week 104 Number Analyzed 8 participants
6.5  (9.04)
HDL-C Week 156 Number Analyzed 8 participants
5.2  (9.50)
HDL-C Week 208 Number Analyzed 7 participants
4.9  (4.91)
HDL-C Week 260 Number Analyzed 5 participants
3.4  (8.96)
HDL-C EOS Number Analyzed 7 participants
6.7  (9.02)
LDL-C Week 12 Number Analyzed 8 participants
-34.1  (37.54)
LDL-C Week 24 Number Analyzed 8 participants
-68.5  (40.22)
LDL-C Week 52 Number Analyzed 7 participants
-78.5  (50.91)
LDL-C Week 104 Number Analyzed 8 participants
-68.7  (43.11)
LDL-C Week 156 Number Analyzed 8 participants
-40.8  (38.91)
LDL-C Week 208 Number Analyzed 7 participants
-20.5  (66.41)
LDL-C Week 260 Number Analyzed 5 participants
-43.4  (44.05)
LDL-C EOS Number Analyzed 7 participants
-35.0  (42.27)
TG Week 12 Number Analyzed 8 participants
-18.5  (71.93)
TG Week 24 Number Analyzed 8 participants
-17.5  (37.62)
TG Week 52 Number Analyzed 7 participants
-45.2  (66.91)
TG Week 104 Number Analyzed 8 participants
-24.0  (84.25)
TG Week 156 Number Analyzed 8 participants
-11.2  (60.45)
TG Week 208 Number Analyzed 7 participants
5.6  (94.18)
TG Week 260 Number Analyzed 5 participants
-4.8  (66.03)
TG EOS Number Analyzed 7 participants
15.7  (106.54)
7.Secondary Outcome
Title Changes From Baseline In Serum Ferritin
Hide Description Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for serum ferritin. Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time Frame Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the FAS for whom serum ferritin data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: microgram (µg)/L
Week 12 Number Analyzed 8 participants
-37.0  (29.93)
Week 24 Number Analyzed 8 participants
-40.1  (47.27)
Week 52 Number Analyzed 7 participants
-18.1  (32.68)
Week 104 Number Analyzed 8 participants
-22.8  (44.57)
Week 156 Number Analyzed 8 participants
0.0  (34.50)
Week 208 Number Analyzed 7 participants
18.0  (40.41)
Week 260 Number Analyzed 5 participants
63.0  (70.53)
EOS Number Analyzed 7 participants
47.7  (56.06)
8.Secondary Outcome
Title Changes From Baseline In Hs-CRP
Hide Description Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for high sensitivity C-reactive protein (hs-CRP). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time Frame Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the FAS for whom hs-CRP data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: mg/L
Week 12 Number Analyzed 8 participants
-1.41  (3.022)
Week 24 Number Analyzed 8 participants
-1.03  (3.945)
Week 52 Number Analyzed 7 participants
-1.40  (3.245)
Week 104 Number Analyzed 8 participants
-1.50  (4.079)
Week 156 Number Analyzed 8 participants
-1.09  (3.323)
Week 208 Number Analyzed 7 participants
-1.34  (3.674)
Week 260 Number Analyzed 5 participants
-0.16  (0.619)
EOS Number Analyzed 7 participants
-1.33  (2.985)
Time Frame From after first dose administration post-Baseline through EOS during study LAL-CL04
Adverse Event Reporting Description Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
 
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to qow dosing at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
All-Cause Mortality
Open-Label Sebelipase Alfa
Affected / at Risk (%)
Total   0/8 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Open-Label Sebelipase Alfa
Affected / at Risk (%)
Total   1/8 (12.50%) 
Hepatobiliary disorders   
Cholecystitis  1  1/8 (12.50%) 
Cholelithiasis  1 [1]  1/8 (12.50%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
[1]
Cholecystectomy for cholelithiasis
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Open-Label Sebelipase Alfa
Affected / at Risk (%)
Total   8/8 (100.00%) 
Cardiac disorders   
Bradycardia  1  1/8 (12.50%) 
Palpitations  1  2/8 (25.00%) 
Tachycardia  1  2/8 (25.00%) 
Ear and labyrinth disorders   
Ear pain  1  3/8 (37.50%) 
Eye disorders   
Blepharitis  1  1/8 (12.50%) 
Conjunctivitis  1  1/8 (12.50%) 
Dry eye  1  1/8 (12.50%) 
Eye pain  1  1/8 (12.50%) 
Keratitis  1  1/8 (12.50%) 
Occular hyperaemia  1  1/8 (12.50%) 
Vision blurred  1  1/8 (12.50%) 
Gastrointestinal disorders   
Abdominal distension  1  1/8 (12.50%) 
Abdominal pain  1  5/8 (62.50%) 
Abdominal pain upper  1  3/8 (37.50%) 
Diarrhoea  1  4/8 (50.00%) 
Dyspepsia  1  1/8 (12.50%) 
Faeces soft  1  1/8 (12.50%) 
Flatulence  1  1/8 (12.50%) 
Gastrooesophageal reflux disease  1  1/8 (12.50%) 
Malocclusion  1  1/8 (12.50%) 
Nausea  1  5/8 (62.50%) 
Toothache  1  1/8 (12.50%) 
Vomiting  1  2/8 (25.00%) 
General disorders   
Catheter site pain  1  1/8 (12.50%) 
Chest discomfort  1  1/8 (12.50%) 
Chest pain  1  2/8 (25.00%) 
Chills  1  1/8 (12.50%) 
Fatigue  1  3/8 (37.50%) 
Non-cardiac chest pain  1  2/8 (25.00%) 
Pain  1  1/8 (12.50%) 
Pyrexia  1  1/8 (12.50%) 
Hepatobiliary disorders   
Bile duct stone  1  1/8 (12.50%) 
Cholelithiasis  1  1/8 (12.50%) 
Granulomatous liver disease  1  1/8 (12.50%) 
Hepatic pain  1  1/8 (12.50%) 
Immune system disorders   
Hypersensitivity  1  1/8 (12.50%) 
Seasonal allergy  1  1/8 (12.50%) 
Infections and infestations   
Abscess limb  1  1/8 (12.50%) 
Bacterial vaginosis  1 [1]  1/2 (50.00%) 
Cellulitis  1  1/8 (12.50%) 
Ear infection  1  1/8 (12.50%) 
Ear lobe infection  1  1/8 (12.50%) 
Eye infection  1  1/8 (12.50%) 
Folliculitis  1  2/8 (25.00%) 
Fungal skin infection  1  1/8 (12.50%) 
Gastroenteritis  1  1/8 (12.50%) 
Infected dermal cyst  1  2/8 (25.00%) 
Influenza  1  2/8 (25.00%) 
Lower respiratory tract infection  1  1/8 (12.50%) 
Nasopharyngitis  1  1/8 (12.50%) 
Pharyngitis  1  1/8 (12.50%) 
Rash pustular  1  1/8 (12.50%) 
Rhinitis  1  1/8 (12.50%) 
Subcutaneous abscess  1  1/8 (12.50%) 
Upper respiratory tract infection  1  1/8 (12.50%) 
Urinary tract infection  1  1/8 (12.50%) 
Viral upper respiratory tract infection  1  5/8 (62.50%) 
Injury, poisoning and procedural complications   
Arthropod bite  1  1/8 (12.50%) 
Cartilage injury  1  1/8 (12.50%) 
Iliotibial band syndrome  1  1/8 (12.50%) 
Laceration  1  1/8 (12.50%) 
Post procedural haemorrhage  1  1/8 (12.50%) 
Procedural pain  1  1/8 (12.50%) 
Procedural dizziness  1  1/8 (12.50%) 
Sunburn  1  2/8 (25.00%) 
Investigations   
Activated partial thromboplastin time prolonged  1  1/8 (12.50%) 
Blood creatinine increased  1  1/8 (12.50%) 
C-reactive protein increased  1  1/8 (12.50%) 
Eosinophil count increased  1  1/8 (12.50%) 
Low density lipoprotein increased  1  1/8 (12.50%) 
Lymphocyte count increased  1  1/8 (12.50%) 
Mean cell volume increased  1  1/8 (12.50%) 
Prothrombin time abnormal  1  1/8 (12.50%) 
Vitamin B12 decreased  1  1/8 (12.50%) 
White blood cell count increased  1  1/8 (12.50%) 
Metabolism and nutrition disorders   
Decreased appetite  1  1/8 (12.50%) 
Vitamin D deficiency  1  1/8 (12.50%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  4/8 (50.00%) 
Bone pain  1  1/8 (12.50%) 
Limb mass  1  1/8 (12.50%) 
Muscle spasms  1  1/8 (12.50%) 
Muscle twitching  1  1/8 (12.50%) 
Muscular weakness  1  1/8 (12.50%) 
Musculoskeletal pain  1  3/8 (37.50%) 
Myalgia  1  3/8 (37.50%) 
Neck mass  1  1/8 (12.50%) 
Pain in extremity  1  1/8 (12.50%) 
Spinal pain  1  1/8 (12.50%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Lipoma  1  1/8 (12.50%) 
Oral neoplasm benign  1  1/8 (12.50%) 
Nervous system disorders   
Amnesia  1  1/8 (12.50%) 
Clonic convulsion  1  1/8 (12.50%) 
Dizziness  1  1/8 (12.50%) 
Dysarthria  1  1/8 (12.50%) 
Dyskinesia  1  1/8 (12.50%) 
Headache  1  2/8 (25.00%) 
Lethargy  1  1/8 (12.50%) 
Paraesthesia  1  2/8 (25.00%) 
Syncope  1  1/8 (12.50%) 
Tremor  1  1/8 (12.50%) 
Psychiatric disorders   
Depression  1  1/8 (12.50%) 
Respiratory, thoracic and mediastinal disorders   
Choking  1  1/8 (12.50%) 
Cough  1  1/8 (12.50%) 
Dyspnoea  1  2/8 (25.00%) 
Epistaxis  1  1/8 (12.50%) 
Laryngeal oedema  1  1/8 (12.50%) 
Oropharyngeal pain  1  3/8 (37.50%) 
Rhinorrhoea  1  2/8 (25.00%) 
Skin and subcutaneous tissue disorders   
Acne  1  1/8 (12.50%) 
Dermal cyst  1  1/8 (12.50%) 
Dermatitis acneiform  1  1/8 (12.50%) 
Eczema  1  1/8 (12.50%) 
Ephelides  1  1/8 (12.50%) 
Pigmentation disorder  1  1/8 (12.50%) 
Pruritus  1  1/8 (12.50%) 
Rash macular  1  1/8 (12.50%) 
Skin lesion  1  1/8 (12.50%) 
Skin mass  1  3/8 (37.50%) 
Vascular disorders   
Flushing  1  1/8 (12.50%) 
Hyperaemia  1  1/8 (12.50%) 
Hypertension  1  1/8 (12.50%) 
Orthostatic hypotension  1  1/8 (12.50%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
[1]
Affects only female participants
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.
Results Point of Contact
Name/Title: Alexion Pharmaceuticals Inc.
Organization: Alexion Pharmaceuticals Inc.
Phone: 475-230-2596
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01488097     History of Changes
Other Study ID Numbers: LAL-CL04
First Submitted: November 26, 2011
First Posted: December 8, 2011
Results First Submitted: January 14, 2016
Results First Posted: May 9, 2016
Last Update Posted: July 20, 2018