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Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency

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ClinicalTrials.gov Identifier: NCT01371825
Recruitment Status : Completed
First Posted : June 13, 2011
Results First Posted : April 18, 2016
Last Update Posted : January 30, 2019
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 Lysosomal Acid Lipase Deficiency
Wolman Disease
Intervention Drug: Sebelipase alfa (SBC-102)
Enrollment 9
Recruitment Details A total of 8 centers participated in this study in the United Kingdom (UK), United States (US), France, Turkey, Ireland, and Egypt.
Pre-assignment Details To assess eligibility, participants were screened for a period of up to 3 weeks prior to enrollment. 11 participants were screened, and 2 participants died during screening. The other 9 participants, all of whom were ≤8 months of age on the date of enrollment, met all eligibility criteria and were enrolled, treated, and analyzed.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) once weekly (qw) and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Period Title: Overall Study
Started 9
Received at Least 1 Dose of Study Drug 9
Completed 5
Not Completed 4
Reason Not Completed
Death             4
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Baseline Participants 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
<=18 years
9
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Months
Number Analyzed 9 participants
3.41
(1.1 to 5.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
4
  44.4%
Male
5
  55.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
6
  66.7%
Unknown or Not Reported
3
  33.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
  11.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
  11.1%
White
4
  44.4%
More than one race
0
   0.0%
Unknown or Not Reported
3
  33.3%
1.Primary Outcome
Title Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age
Hide Description The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The PES included participants who received any amount of sebelipase alfa and who were ≤8 months of age on the date of their first infusion of sebelipase alfa. All 9 participants were included in the PES.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Participants Analyzed 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
67
(29.9 to 92.5)
2.Secondary Outcome
Title Percentage Of Participants Surviving Beyond 12 Months Of Age
Hide Description The percentage of participants in the PES who survived to at least 18 months of age.
Time Frame Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable participants in the PES, which included participants who received any amount of sebelipase alfa and who were ≤ 8 months of age on the date of their first infusion of sebelipase alfa. There were 2 non-evaluable participants at Month 60, defined as participants who were alive, still in the study, and had not yet reached 60 months of age.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Participants Analyzed 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Survival Through 18 Months of Age Number Analyzed 9 participants
56
(21.2 to 86.3)
Survival Through 24 Months of Age Number Analyzed 9 participants
56
(21.2 to 86.3)
Survival Through 36 Months of Age Number Analyzed 9 participants
56
(21.2 to 86.3)
Survival Through 48 Months of Age Number Analyzed 9 participants
56
(21.2 to 86.3)
Survival Through 60 Months of Age Number Analyzed 7 participants
43
(9.9 to 81.6)
3.Secondary Outcome
Title Median Age At Death
Hide Description Participants in the PES who died during the study, including 3 participants who died after having received between 1 and 4 infusions of sebelipase alfa and 1 participant who died after approximately 40 weeks on treatment.
Time Frame Baseline to Week 260
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PES who died during the study were included in this analysis. The PES included all 9 participants who received any amount of sebelipase alfa and who were ≤8 months of age on the date of their first infusion of sebelipase alfa.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Participants Analyzed 4
Median (Full Range)
Unit of Measure: months
3.63
(2.8 to 15.0)
4.Secondary Outcome
Title Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles
Hide Description Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.
Time Frame Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
The PES included participants who received any amount of sebelipase alfa and who were ≤8 months of age on the date of their first infusion of sebelipase alfa. All 9 participants were included in the PES.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Participants Analyzed 9
Median (Full Range)
Unit of Measure: WFA Percentile
Month 12 Number Analyzed 4 participants
7.469
(5.35 to 13.77)
Month 24 Number Analyzed 5 participants
21.787
(0.91 to 30.37)
Month 36 Number Analyzed 5 participants
14.037
(-0.35 to 89.00)
Month 48 Number Analyzed 5 participants
15.770
(4.06 to 86.50)
Month 60 Number Analyzed 5 participants
19.869
(7.36 to 71.39)
5.Secondary Outcome
Title Number Of Participants With Stunting, Wasting, Or Underweight
Hide Description

The number of participants who met criteria for the following dichotomous indicators of under nutrition were reported. These indicators included the following:

  • Stunting was defined as at least 2 standard deviations below the median for length-for-age/height-for-age;
  • Wasting was defined as wasting at least 2 standard deviations below the median for weight-for-length/weight-for-height; and
  • Underweight was defined as at least 2 standard deviations below the median for WFA.
Time Frame Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
The PES included participants who received any amount of sebelipase alfa and who were ≤8 months of age on the date of their first infusion of sebelipase alfa. All 9 participants were included in the PES.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
Stunting, Baseline Number Analyzed 8 participants
4
  50.0%
Stunting, Month 12 Number Analyzed 4 participants
1
  25.0%
Stunting, Month 24 Number Analyzed 5 participants
0
   0.0%
Stunting, Month 36 Number Analyzed 5 participants
0
   0.0%
Stunting, Month 48 Number Analyzed 5 participants
0
   0.0%
Stunting, Month 60 Number Analyzed 5 participants
0
   0.0%
Wasting, Baseline Number Analyzed 8 participants
2
  25.0%
Wasting, Month 12 Number Analyzed 4 participants
0
   0.0%
Wasting, Month 24 Number Analyzed 5 participants
0
   0.0%
Wasting, Month 36 Number Analyzed 5 participants
0
   0.0%
Wasting, Month 48 Number Analyzed 5 participants
0
   0.0%
Wasting, Month 60 Number Analyzed 5 participants
0
   0.0%
Underweight, Baseline Number Analyzed 9 participants
2
  22.2%
Underweight, Month 12 Number Analyzed 4 participants
0
   0.0%
Underweight, Month 24 Number Analyzed 5 participants
1
  20.0%
Underweight, Month 36 Number Analyzed 5 participants
0
   0.0%
Underweight, Month 48 Number Analyzed 5 participants
0
   0.0%
Underweight, Month 60 Number Analyzed 5 participants
0
   0.0%
No Stunting, Wasting, or Underweight, Baseline Number Analyzed 9 participants
4
  44.4%
No Stunting, Wasting, or Underweight, Month 12 Number Analyzed 4 participants
3
  75.0%
No Stunting, Wasting, or Underweight, Month 24 Number Analyzed 5 participants
4
  80.0%
No Stunting, Wasting, or Underweight, Month 36 Number Analyzed 5 participants
5
 100.0%
No Stunting, Wasting, or Underweight, Month 48 Number Analyzed 5 participants
5
 100.0%
No Stunting, Wasting, or Underweight, Month 60 Number Analyzed 5 participants
5
 100.0%
6.Secondary Outcome
Title Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)
Hide Description Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Time Frame Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
The PES included participants who received any amount of sebelipase alfa and who were ≤8 months of age on the date of their first infusion of sebelipase alfa. All 9 participants were included in the PES.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Participants Analyzed 9
Median (Full Range)
Unit of Measure: units/Liter (U/L)
ALT, Month 12 Number Analyzed 4 participants
-13.50
(-121.00 to 12.00)
ALT, Month 24 Number Analyzed 5 participants
-5.00
(-111.00 to 228.00)
ALT, Month 36 Number Analyzed 5 participants
-4.00
(-100.00 to 107.0)
ALT, Month 48 Number Analyzed 4 participants
-27.50
(-129.00 to -2.00)
ALT, Month 60 Number Analyzed 4 participants
-27.00
(-122.00 to 2.00)
AST, Month 12 Number Analyzed 4 participants
-43.50
(-62.00 to -29.00)
AST, Month 24 Number Analyzed 5 participants
-30.00
(-49.00 to 67.00)
AST, Month 36 Number Analyzed 4 participants
-33.00
(-49.00 to 86.00)
AST, Month 48 Number Analyzed 5 participants
-51.00
(-67.00 to -31.00)
AST, Month 60 Number Analyzed 4 participants
-40.00
(-84.00 to -17.00)
7.Secondary Outcome
Title Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin
Hide Description The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.
Time Frame Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
The PES included participants who received any amount of sebelipase alfa and who were ≤8 months of age on the date of their first infusion of sebelipase alfa. All 9 participants were included in the PES.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Participants Analyzed 9
Median (Full Range)
Unit of Measure: micrograms/Liter (µg/L)
Month 12 Number Analyzed 3 participants
-294.40
(-562.2 to -271.0)
Month 24 Number Analyzed 3 participants
-239.00
(-298.0 to -235.0)
Month 36 Number Analyzed 4 participants
-262.95
(-566.6 to -166.0)
Month 48 Number Analyzed 3 participants
-268.00
(-278.0 to -179.0)
Month 60 Number Analyzed 3 participants
-213.00
(-543.9 to -155.0)
8.Secondary Outcome
Title Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN]
Hide Description

The number of participants achieving and maintaining TFHN are presented.

For TFHN to be achieved, the participant must a) have had 2 post-baseline measurements of hemoglobin at least 4 weeks apart that were both above the age-adjusted lower limit of normal; b) have had no known additional measurements of hemoglobin that were below the age-adjusted lower limit of normal during the (minimum) 4-week period; and c) have had no transfusions during the (minimum) 4-week period, and also no transfusions for 2 weeks prior to the first hemoglobin measurement in the (minimum) 4-week period.

For TFHN to be maintained, the participant must have been transfusion-free beginning at Week 6 and had all hemoglobin assessments above the lower limit of normal beginning in Week 8 and lasting at least 13 weeks.

Time Frame Baseline to Month 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PES who received treatment with sebelipase alfa for at least 4 weeks (and could therefore be assessed for short-term TFHN). The PES included participants who received any amount of sebelipase alfa and who were ≤ 8 months of age on the date of their first infusion of sebelipase alfa.
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description:
Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
Achieved TFHN
6
  66.7%
Maintained TFHN
2
  22.2%
Time Frame Week 260
Adverse Event Reporting Description Adverse events were obtained through spontaneous reporting or were elicited by specific questioning of the participant's parent or legal guardian. Treatment-emergent adverse events included events with an onset at or following the start of treatment with study drug or that worsened in severity or relationship at or following the start of treatment, and occurring up to 30 days after the last infusion of sebelipase alfa.
 
Arm/Group Title Open-Label Sebelipase Alfa
Hide Arm/Group Description Participants received IV infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 mg/kg qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant’s dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to a qow dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
All-Cause Mortality
Open-Label Sebelipase Alfa
Affected / at Risk (%)
Total   4/9 (44.44%) 
Show Serious Adverse Events Hide Serious Adverse Events
Open-Label Sebelipase Alfa
Affected / at Risk (%)
Total   9/9 (100.00%) 
Blood and lymphatic system disorders   
Lymphadenopathy  1  1/9 (11.11%) 
Cardiac disorders   
Cardiac arrest  1  1/9 (11.11%) 
Tachycardia  1  1/9 (11.11%) 
Gastrointestinal disorders   
Diarrhoea  1  1/9 (11.11%) 
Peritoneal haemorrhage  1  1/9 (11.11%) 
Malabsorption  1  1/9 (11.11%) 
Vomiting  1  1/9 (11.11%) 
General disorders   
Chills  1  1/9 (11.11%) 
Pyrexia  1  3/9 (33.33%) 
Hyperthermia  1  1/9 (11.11%) 
Sudden cardiac death  1  1/9 (11.11%) 
Hepatobiliary disorders   
Hepatic failure  1  1/9 (11.11%) 
Infections and infestations   
Bacterial pyelonephritis  1  1/9 (11.11%) 
Catheter site infection  1  2/9 (22.22%) 
Device related infection  1  2/9 (22.22%) 
Device related sepsis  1  1/9 (11.11%) 
Respiratory tract infection  1  1/9 (11.11%) 
Roseola  1  1/9 (11.11%) 
Staphylococcal bacteraemia  1  1/9 (11.11%) 
Staphylococcal sepsis  1  1/9 (11.11%) 
Upper respiratory tract infection  1  1/9 (11.11%) 
Viral infection  1  2/9 (22.22%) 
Adenovirus infection  1  1/9 (11.11%) 
Amoebic dysentery  1  1/9 (11.11%) 
Croup infectious  1  1/9 (11.11%) 
Gastroenteritis  1  1/9 (11.11%) 
Rotavirus infection  1  1/9 (11.11%) 
Investigations   
Weight decreased  1  1/9 (11.11%) 
Metabolism and nutrition disorders   
Dehydration  1  1/9 (11.11%) 
Failure to thrive  1  1/9 (11.11%) 
Food intolerance  1  1/9 (11.11%) 
Metabolic acidosis  1  1/9 (11.11%) 
Vascular disorders   
Pallor  1  1/9 (11.11%) 
Poor venous access  1  1/9 (11.11%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
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   9/9 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  4/9 (44.44%) 
Thrombocytopenia  1  1/9 (11.11%) 
Lymphadenopathy  1  1/9 (11.11%) 
Lymphopenia  1  1/9 (11.11%) 
Iron deficiency anaemia  1  2/9 (22.22%) 
Cardiac disorders   
Tachycardia  1  2/9 (22.22%) 
Bradycardia  1  2/9 (22.22%) 
Cardiovascular disorder  1  1/9 (11.11%) 
Congenital, familial and genetic disorders   
Hydrocele  1  2/9 (22.22%) 
Ear and labyrinth disorders   
Ear pain  1  2/9 (22.22%) 
Middle ear inflammation  1  1/9 (11.11%) 
Endocrine disorders   
Adrenal insufficiency  1  1/9 (11.11%) 
Eye disorders   
Conjunctivitis  1  1/9 (11.11%) 
Pupillary disorder  1  1/9 (11.11%) 
Gastrointestinal disorders   
Vomiting  1  6/9 (66.67%) 
Diarrhoea  1  6/9 (66.67%) 
Abdominal distension  1  1/9 (11.11%) 
Nausea  1  1/9 (11.11%) 
Teething  1  3/9 (33.33%) 
Ascites  1  1/9 (11.11%) 
Faeces discoloured  1  1/9 (11.11%) 
Gastrooesophageal reflux disease  1  2/9 (22.22%) 
Haematochezia  1  2/9 (22.22%) 
Post-tussive vomiting  1  1/9 (11.11%) 
Retching  1  1/9 (11.11%) 
Tongue dicolouration  1  1/9 (11.11%) 
Umbilical hernia  1  1/9 (11.11%) 
Abdominal discomfort  1  1/9 (11.11%) 
Abdominal pain upper  1  1/9 (11.11%) 
Abdominal pain  1  3/9 (33.33%) 
Constipation  1  1/9 (11.11%) 
Dental caries  1  1/9 (11.11%) 
Enteritis  1  1/9 (11.11%) 
Flatulence  1  1/9 (11.11%) 
Gastritis  1  1/9 (11.11%) 
General disorders   
Pyrexia  1  5/9 (55.56%) 
Chills  1  1/9 (11.11%) 
Hyperthermia  1  1/9 (11.11%) 
Catheter site rash  1  1/9 (11.11%) 
Disease progression  1  1/9 (11.11%) 
Infusion Site Extravasation  1  1/9 (11.11%) 
Feeling abnormal  1  1/9 (11.11%) 
Gait disturbance  1  1/9 (11.11%) 
Granuloma  1  1/9 (11.11%) 
Infusion site oedema  1  1/9 (11.11%) 
Irritability  1  1/9 (11.11%) 
Oedema peripheral  1  1/9 (11.11%) 
Pain  1  1/9 (11.11%) 
Asthenia  1  1/9 (11.11%) 
Catheter site pain  1  1/9 (11.11%) 
Catheter site swelling  1  1/9 (11.11%) 
Swelling  1  1/9 (11.11%) 
Hepatobiliary disorders   
Cholelithiasis  1  1/9 (11.11%) 
Hyperbilirubinaemia  1  1/9 (11.11%) 
Infections and infestations   
Rhinitis  1  5/9 (55.56%) 
Nasopharyngitis  1  5/9 (55.56%) 
Device related infection  1  2/9 (22.22%) 
Ear infection viral  1  2/9 (22.22%) 
Bronchiolitis  1  2/9 (22.22%) 
Catheter site infection  1  2/9 (22.22%) 
Gastroenteritis  1  4/9 (44.44%) 
Pharyngitis  1  3/9 (33.33%) 
Varicella  1  3/9 (33.33%) 
Bacterial infection  1  1/9 (11.11%) 
Bronchitis  1  1/9 (11.11%) 
Candida nappy rash  1  1/9 (11.11%) 
Escherichia urinary tract infection  1  1/9 (11.11%) 
Eyelid infection  1  1/9 (11.11%) 
Fungal infection  1  1/9 (11.11%) 
Metapneumovirus infection  1  1/9 (11.11%) 
Oral candidiasis  1  1/9 (11.11%) 
Oral fungal infection  1  1/9 (11.11%) 
Oral herpes  1  1/9 (11.11%) 
Otitis media  1  1/9 (11.11%) 
Post procedural infection  1  1/9 (11.11%) 
Rash pustular  1  1/9 (11.11%) 
Staphylococcal skin infection  1  1/9 (11.11%) 
Upper respiratory tract infection  1  1/9 (11.11%) 
Viral infection  1  3/9 (33.33%) 
Angular cheilitis  1  1/9 (11.11%) 
Croup infectious  1  1/9 (11.11%) 
Gastroenteritis viral  1  1/9 (11.11%) 
Infectious mononucleosis  1  1/9 (11.11%) 
Influenza  1  1/9 (11.11%) 
Scarlet fever  1  1/9 (11.11%) 
Stoma site candida  1  1/9 (11.11%) 
Tonsillitis  1  1/9 (11.11%) 
Fungal skin infection  1  2/9 (22.22%) 
Hand-foot-and-mouth disease  1  2/9 (22.22%) 
Urinary tract infection  1  2/9 (22.22%) 
Ear infection  1  3/9 (33.33%) 
Conjunctivitis  1  2/9 (22.22%) 
Injury, poisoning and procedural complications   
Contusion  1  1/9 (11.11%) 
Endotracheal intubation complication  1  1/9 (11.11%) 
Limb injury  1  1/9 (11.11%) 
Mouth injury  1  1/9 (11.11%) 
Post procedural discharge  1  1/9 (11.11%) 
Postoperative ileus  1  1/9 (11.11%) 
Fall  1  1/9 (11.11%) 
Head injury  1  1/9 (11.11%) 
Laceration  1  1/9 (11.11%) 
Stoma site inflammation  1  1/9 (11.11%) 
Tooth injury  1  1/9 (11.11%) 
Investigations   
Staphylococcus test positive  1  1/9 (11.11%) 
Blood immunoglobulin A abnormal  1  1/9 (11.11%) 
Blood immunoglobulin G abnormal  1  1/9 (11.11%) 
Blood lactate dehydrogenase increased  1  1/9 (11.11%) 
Blood potassium decreased  1  1/9 (11.11%) 
Blood urea increased  1  1/9 (11.11%) 
Body temperature increased  1  1/9 (11.11%) 
Neutrophil count increased  1  1/9 (11.11%) 
Norovirus test positive  1  1/9 (11.11%) 
Oxygen saturation decreased  1  1/9 (11.11%) 
Platelet count increased  1  1/9 (11.11%) 
Respiratory syncytial virus test positive  1  1/9 (11.11%) 
Serum ferritin increased  1  1/9 (11.11%) 
Transaminases increased  1  1/9 (11.11%) 
Urine albumin/creatinine ratio increased  1  1/9 (11.11%) 
Urine output decreased  1  1/9 (11.11%) 
Vitamin D decreased  1  1/9 (11.11%) 
Lymphocyte count increased  1  1/9 (11.11%) 
Lymphocyte count abnormal  1  1/9 (11.11%) 
Monocyte count increased  1  1/9 (11.11%) 
Adenovirus test positive  1  1/9 (11.11%) 
Blood immunoglobulin G decreased  1  1/9 (11.11%) 
Blood albumin decreased  1  2/9 (22.22%) 
Clostridium test positive  1  1/9 (11.11%) 
Parasite stool test positive  1  1/9 (11.11%) 
Pseudomonas test positive  1  1/9 (11.11%) 
Respirovirus test positive  1  1/9 (11.11%) 
Vitamin E decreased  1  1/9 (11.11%) 
Protein total decreased  1  2/9 (22.22%) 
Metabolism and nutrition disorders   
Decreased appetite  1  2/9 (22.22%) 
Dehydration  1  1/9 (11.11%) 
Hypercalcaemia  1  1/9 (11.11%) 
Hyperglycaemia  1  1/9 (11.11%) 
Hypernatraemia  1  1/9 (11.11%) 
Hypocalcaemia  1  1/9 (11.11%) 
Hypophosphataemia  1  1/9 (11.11%) 
Hypoproteinaemia  1  1/9 (11.11%) 
Hypovolaemia  1  1/9 (11.11%) 
Iron deficiency  1  1/9 (11.11%) 
Metabolic acidosis  1  1/9 (11.11%) 
Vitamin D deficiency  1  3/9 (33.33%) 
Vitamin A deficiency  1  1/9 (11.11%) 
Vitamin E deficiency  1  2/9 (22.22%) 
Vitamin K deficiency  1  2/9 (22.22%) 
Musculoskeletal and connective tissue disorders   
Myalgia  1  1/9 (11.11%) 
Nervous system disorders   
Hypotonia  1  1/9 (11.11%) 
Headache  1  1/9 (11.11%) 
Product Issues   
Device dislocation  1  1/9 (11.11%) 
Device malfunction  1  1/9 (11.11%) 
Psychiatric disorders   
Agitation  1  1/9 (11.11%) 
Irritability  1  1/9 (11.11%) 
Emotional disorder  1  1/9 (11.11%) 
Renal and urinary disorders   
Dysuria  1  1/9 (11.11%) 
Reproductive system and breast disorders   
Penile blister  1 [1]  1/5 (20.00%) 
Genital rash  1  1/9 (11.11%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  5/9 (55.56%) 
Rhinorrhoea  1  2/9 (22.22%) 
Pharyngeal erythema  1  1/9 (11.11%) 
Respiratory failure  1  1/9 (11.11%) 
Sneezing  1  1/9 (11.11%) 
Tonsillar disorder  1  1/9 (11.11%) 
Use of accessory respiratory muscles  1  1/9 (11.11%) 
Wheezing  1  1/9 (11.11%) 
Respiratory distress  1  1/9 (11.11%) 
Productive cough  1  1/9 (11.11%) 
Tachypnoea  1  1/9 (11.11%) 
Tonsillar hypertrophy  1  1/9 (11.11%) 
Oropharyngeal pain  1  2/9 (22.22%) 
Skin and subcutaneous tissue disorders   
Dermatitis diaper  1  4/9 (44.44%) 
Rash  1  3/9 (33.33%) 
Urticaria  1  3/9 (33.33%) 
Eczema  1  3/9 (33.33%) 
Pruritus generalised  1  1/9 (11.11%) 
Umbilical erythema  1  1/9 (11.11%) 
Petechiae  1  1/9 (11.11%) 
Pruritus  1  1/9 (11.11%) 
Rash macular  1  1/9 (11.11%) 
Skin discolouration  1  1/9 (11.11%) 
Skin irritation  1  1/9 (11.11%) 
Xanthoma  1  1/9 (11.11%) 
Erythema  1  2/9 (22.22%) 
Vascular disorders   
Hypotension  1  1/9 (11.11%) 
Hypertension  1  1/9 (11.11%) 
Pallor  1  1/9 (11.11%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
[1]
The AE of penile blister can only affect males, and there are 5 total males exposed.
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.
Phone: 855-752-2356
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01371825     History of Changes
Other Study ID Numbers: LAL-CL03
First Submitted: June 9, 2011
First Posted: June 13, 2011
Results First Submitted: January 14, 2016
Results First Posted: April 18, 2016
Last Update Posted: January 30, 2019