Trial Outcomes & Findings for Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency (NCT NCT01371825)

NCT ID: NCT01371825

Last Updated: 2019-01-30

Results Overview

The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 9 participants
• Primary outcome timeframe: Month 12
• Results posted on: 2019-01-30

Participant Flow

A total of 8 centers participated in this study in the United Kingdom (UK), United States (US), France, Turkey, Ireland, and Egypt.

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.

Participant milestones

Measure	Open-Label Sebelipase Alfa 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.
Overall Study STARTED	9
Overall Study Received at Least 1 Dose of Study Drug	9
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure

Open-Label Sebelipase Alfa 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.

Overall Study Death

4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Open-Label Sebelipase Alfa n=9 Participants 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.
Age, Categorical <=18 years	9 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	3.41 months n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 12

Population: 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.

The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.

Outcome measures

Measure

Open-Label Sebelipase Alfa n=9 Participants 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.

Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age

67 Percentage of participants Interval 29.9 to 92.5

SECONDARY outcome

Timeframe: Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60

Population: 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.

The percentage of participants in the PES who survived to at least 18 months of age.

Outcome measures

Measure	Open-Label Sebelipase Alfa n=9 Participants 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.
Percentage Of Participants Surviving Beyond 12 Months Of Age Survival Through 18 Months of Age	56 Percentage of participants Interval 21.2 to 86.3
Percentage Of Participants Surviving Beyond 12 Months Of Age Survival Through 24 Months of Age	56 Percentage of participants Interval 21.2 to 86.3
Percentage Of Participants Surviving Beyond 12 Months Of Age Survival Through 36 Months of Age	56 Percentage of participants Interval 21.2 to 86.3
Percentage Of Participants Surviving Beyond 12 Months Of Age Survival Through 48 Months of Age	56 Percentage of participants Interval 21.2 to 86.3
Percentage Of Participants Surviving Beyond 12 Months Of Age Survival Through 60 Months of Age	43 Percentage of participants Interval 9.9 to 81.6

SECONDARY outcome

Timeframe: Baseline to Week 260

Population: 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.

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.

Outcome measures

Measure

Open-Label Sebelipase Alfa n=4 Participants 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.

Median Age At Death

3.63 months Interval 2.8 to 15.0

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

Population: 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.

Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.

Outcome measures

Measure	Open-Label Sebelipase Alfa n=9 Participants 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.
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles Month 12	7.469 WFA Percentile Interval 5.35 to 13.77
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles Month 24	21.787 WFA Percentile Interval 0.91 to 30.37
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles Month 36	14.037 WFA Percentile Interval -0.35 to 89.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles Month 48	15.770 WFA Percentile Interval 4.06 to 86.5
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles Month 60	19.869 WFA Percentile Interval 7.36 to 71.39

SECONDARY outcome

Timeframe: Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60

Population: 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.

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.

Outcome measures

Measure	Open-Label Sebelipase Alfa n=9 Participants 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.
Number Of Participants With Stunting, Wasting, Or Underweight Stunting, Baseline	4 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Stunting, Month 12	1 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Stunting, Month 24	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Stunting, Month 36	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Stunting, Month 48	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Stunting, Month 60	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Wasting, Baseline	2 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Wasting, Month 12	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Wasting, Month 24	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Wasting, Month 36	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Wasting, Month 48	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Wasting, Month 60	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Underweight, Baseline	2 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Underweight, Month 12	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Underweight, Month 24	1 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Underweight, Month 36	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Underweight, Month 48	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight Underweight, Month 60	0 Participants
Number Of Participants With Stunting, Wasting, Or Underweight No Stunting, Wasting, or Underweight, Baseline	4 Participants
Number Of Participants With Stunting, Wasting, Or Underweight No Stunting, Wasting, or Underweight, Month 12	3 Participants
Number Of Participants With Stunting, Wasting, Or Underweight No Stunting, Wasting, or Underweight, Month 24	4 Participants
Number Of Participants With Stunting, Wasting, Or Underweight No Stunting, Wasting, or Underweight, Month 36	5 Participants
Number Of Participants With Stunting, Wasting, Or Underweight No Stunting, Wasting, or Underweight, Month 48	5 Participants
Number Of Participants With Stunting, Wasting, Or Underweight No Stunting, Wasting, or Underweight, Month 60	5 Participants

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

Population: 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.

Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Outcome measures

Measure	Open-Label Sebelipase Alfa n=9 Participants 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.
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) ALT, Month 60	-27.00 units/Liter (U/L) Interval -122.0 to 2.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) ALT, Month 12	-13.50 units/Liter (U/L) Interval -121.0 to 12.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) ALT, Month 24	-5.00 units/Liter (U/L) Interval -111.0 to 228.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) ALT, Month 36	-4.00 units/Liter (U/L) Interval -100.0 to 107.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) ALT, Month 48	-27.50 units/Liter (U/L) Interval -129.0 to -2.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) AST, Month 12	-43.50 units/Liter (U/L) Interval -62.0 to -29.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) AST, Month 24	-30.00 units/Liter (U/L) Interval -49.0 to 67.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) AST, Month 36	-33.00 units/Liter (U/L) Interval -49.0 to 86.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) AST, Month 48	-51.00 units/Liter (U/L) Interval -67.0 to -31.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST) AST, Month 60	-40.00 units/Liter (U/L) Interval -84.0 to -17.0

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

Population: 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.

The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.

Outcome measures

Measure	Open-Label Sebelipase Alfa n=9 Participants 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.
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin Month 12	-294.40 micrograms/Liter (µg/L) Interval -562.2 to -271.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin Month 24	-239.00 micrograms/Liter (µg/L) Interval -298.0 to -235.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin Month 36	-262.95 micrograms/Liter (µg/L) Interval -566.6 to -166.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin Month 48	-268.00 micrograms/Liter (µg/L) Interval -278.0 to -179.0
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin Month 60	-213.00 micrograms/Liter (µg/L) Interval -543.9 to -155.0

SECONDARY outcome

Timeframe: Baseline to Month 60

Population: 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.

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.

Outcome measures

Measure	Open-Label Sebelipase Alfa n=9 Participants 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.
Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN] Achieved TFHN	6 Participants
Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN] Maintained TFHN	2 Participants

Adverse Events

Open-Label Sebelipase Alfa

Serious events: 9 serious events

Other events: 9 other events

Deaths: 4 deaths

Serious adverse events

Measure	Open-Label Sebelipase Alfa n=9 participants at risk 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.
Vascular disorders Pallor	11.1% 1/9 • Week 260 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.
General disorders Chills	11.1% 1/9 • Week 260 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.
General disorders Pyrexia	33.3% 3/9 • Week 260 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.
Blood and lymphatic system disorders Lymphadenopathy	11.1% 1/9 • Week 260 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.
Cardiac disorders Cardiac arrest	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Diarrhoea	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Peritoneal haemorrhage	11.1% 1/9 • Week 260 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.
General disorders Hyperthermia	11.1% 1/9 • Week 260 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.
Hepatobiliary disorders Hepatic failure	11.1% 1/9 • Week 260 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.
Infections and infestations Bacterial pyelonephritis	11.1% 1/9 • Week 260 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.
Infections and infestations Catheter site infection	22.2% 2/9 • Week 260 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.
Infections and infestations Device related infection	22.2% 2/9 • Week 260 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.
Infections and infestations Device related sepsis	11.1% 1/9 • Week 260 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.
Infections and infestations Respiratory tract infection	11.1% 1/9 • Week 260 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.
Infections and infestations Roseola	11.1% 1/9 • Week 260 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.
Infections and infestations Staphylococcal bacteraemia	11.1% 1/9 • Week 260 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.
Infections and infestations Staphylococcal sepsis	11.1% 1/9 • Week 260 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.
Infections and infestations Upper respiratory tract infection	11.1% 1/9 • Week 260 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.
Infections and infestations Viral infection	22.2% 2/9 • Week 260 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.
Investigations Weight decreased	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Dehydration	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Failure to thrive	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Food intolerance	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Metabolic acidosis	11.1% 1/9 • Week 260 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.
Vascular disorders Poor venous access	11.1% 1/9 • Week 260 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.
Cardiac disorders Tachycardia	11.1% 1/9 • Week 260 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.
General disorders Sudden cardiac death	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Malabsorption	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Vomiting	11.1% 1/9 • Week 260 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.
Infections and infestations Adenovirus infection	11.1% 1/9 • Week 260 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.
Infections and infestations Amoebic dysentery	11.1% 1/9 • Week 260 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.
Infections and infestations Croup infectious	11.1% 1/9 • Week 260 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.
Infections and infestations Gastroenteritis	11.1% 1/9 • Week 260 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.
Infections and infestations Rotavirus infection	11.1% 1/9 • Week 260 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.

Other adverse events

Measure	Open-Label Sebelipase Alfa n=9 participants at risk 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.
Investigations Platelet count increased	11.1% 1/9 • Week 260 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.
Investigations Respiratory syncytial virus test positive	11.1% 1/9 • Week 260 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.
Investigations Serum ferritin increased	11.1% 1/9 • Week 260 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.
Investigations Transaminases increased	11.1% 1/9 • Week 260 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.
Investigations Urine albumin/creatinine ratio increased	11.1% 1/9 • Week 260 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.
Investigations Urine output decreased	11.1% 1/9 • Week 260 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.
Investigations Vitamin D decreased	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Decreased appetite	22.2% 2/9 • Week 260 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.
Metabolism and nutrition disorders Dehydration	11.1% 1/9 • Week 260 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.
Blood and lymphatic system disorders Anaemia	44.4% 4/9 • Week 260 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.
Blood and lymphatic system disorders Thrombocytopenia	11.1% 1/9 • Week 260 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.
Cardiac disorders Tachycardia	22.2% 2/9 • Week 260 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.
Cardiac disorders Bradycardia	22.2% 2/9 • Week 260 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.
Cardiac disorders Cardiovascular disorder	11.1% 1/9 • Week 260 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.
Congenital, familial and genetic disorders Hydrocele	22.2% 2/9 • Week 260 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.
Ear and labyrinth disorders Ear pain	22.2% 2/9 • Week 260 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.
Ear and labyrinth disorders Middle ear inflammation	11.1% 1/9 • Week 260 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.
Endocrine disorders Adrenal insufficiency	11.1% 1/9 • Week 260 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.
Eye disorders Conjunctivitis	11.1% 1/9 • Week 260 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.
Eye disorders Pupillary disorder	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Vomiting	66.7% 6/9 • Week 260 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.
Gastrointestinal disorders Diarrhoea	66.7% 6/9 • Week 260 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.
Gastrointestinal disorders Abdominal distension	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Nausea	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Teething	33.3% 3/9 • Week 260 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.
Gastrointestinal disorders Ascites	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Faeces discoloured	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Gastrooesophageal reflux disease	22.2% 2/9 • Week 260 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.
Gastrointestinal disorders Haematochezia	22.2% 2/9 • Week 260 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.
Gastrointestinal disorders Post-tussive vomiting	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Retching	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Tongue dicolouration	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Umbilical hernia	11.1% 1/9 • Week 260 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.
General disorders Pyrexia	55.6% 5/9 • Week 260 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.
General disorders Chills	11.1% 1/9 • Week 260 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.
General disorders Hyperthermia	11.1% 1/9 • Week 260 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.
General disorders Catheter site rash	11.1% 1/9 • Week 260 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.
Product Issues Device dislocation	11.1% 1/9 • Week 260 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.
General disorders Disease progression	11.1% 1/9 • Week 260 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.
General disorders Infusion Site Extravasation	11.1% 1/9 • Week 260 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.
General disorders Feeling abnormal	11.1% 1/9 • Week 260 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.
General disorders Gait disturbance	11.1% 1/9 • Week 260 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.
General disorders Granuloma	11.1% 1/9 • Week 260 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.
General disorders Infusion site oedema	11.1% 1/9 • Week 260 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.
General disorders Irritability	11.1% 1/9 • Week 260 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.
General disorders Oedema peripheral	11.1% 1/9 • Week 260 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.
General disorders Pain	11.1% 1/9 • Week 260 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.
Hepatobiliary disorders Cholelithiasis	11.1% 1/9 • Week 260 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.
Hepatobiliary disorders Hyperbilirubinaemia	11.1% 1/9 • Week 260 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.
Infections and infestations Rhinitis	55.6% 5/9 • Week 260 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.
Infections and infestations Nasopharyngitis	55.6% 5/9 • Week 260 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.
Infections and infestations Device related infection	22.2% 2/9 • Week 260 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.
Infections and infestations Ear infection viral	22.2% 2/9 • Week 260 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.
Infections and infestations Bronchiolitis	22.2% 2/9 • Week 260 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.
Infections and infestations Catheter site infection	22.2% 2/9 • Week 260 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.
Infections and infestations Gastroenteritis	44.4% 4/9 • Week 260 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.
Infections and infestations Pharyngitis	33.3% 3/9 • Week 260 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.
Infections and infestations Varicella	33.3% 3/9 • Week 260 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.
Infections and infestations Bacterial infection	11.1% 1/9 • Week 260 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.
Infections and infestations Bronchitis	11.1% 1/9 • Week 260 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.
Infections and infestations Candida nappy rash	11.1% 1/9 • Week 260 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.
Infections and infestations Escherichia urinary tract infection	11.1% 1/9 • Week 260 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.
Infections and infestations Eyelid infection	11.1% 1/9 • Week 260 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.
Infections and infestations Fungal infection	11.1% 1/9 • Week 260 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.
Infections and infestations Metapneumovirus infection	11.1% 1/9 • Week 260 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.
Infections and infestations Oral candidiasis	11.1% 1/9 • Week 260 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.
Infections and infestations Oral fungal infection	11.1% 1/9 • Week 260 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.
Infections and infestations Oral herpes	11.1% 1/9 • Week 260 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.
Infections and infestations Otitis media	11.1% 1/9 • Week 260 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.
Infections and infestations Post procedural infection	11.1% 1/9 • Week 260 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.
Infections and infestations Rash pustular	11.1% 1/9 • Week 260 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.
Infections and infestations Staphylococcal skin infection	11.1% 1/9 • Week 260 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.
Infections and infestations Upper respiratory tract infection	11.1% 1/9 • Week 260 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.
Infections and infestations Viral infection	33.3% 3/9 • Week 260 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.
Injury, poisoning and procedural complications Contusion	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Endotracheal intubation complication	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Limb injury	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Mouth injury	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Post procedural discharge	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Postoperative ileus	11.1% 1/9 • Week 260 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.
Investigations Staphylococcus test positive	11.1% 1/9 • Week 260 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.
Investigations Blood immunoglobulin A abnormal	11.1% 1/9 • Week 260 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.
Investigations Blood immunoglobulin G abnormal	11.1% 1/9 • Week 260 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.
Investigations Blood lactate dehydrogenase increased	11.1% 1/9 • Week 260 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.
Investigations Blood potassium decreased	11.1% 1/9 • Week 260 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.
Investigations Blood urea increased	11.1% 1/9 • Week 260 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.
Investigations Body temperature increased	11.1% 1/9 • Week 260 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.
Investigations Neutrophil count increased	11.1% 1/9 • Week 260 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.
Investigations Norovirus test positive	11.1% 1/9 • Week 260 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.
Investigations Oxygen saturation decreased	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Hypercalcaemia	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Hyperglycaemia	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Hypernatraemia	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Hypocalcaemia	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Hypophosphataemia	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Hypoproteinaemia	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Hypovolaemia	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Iron deficiency	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Metabolic acidosis	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Vitamin D deficiency	33.3% 3/9 • Week 260 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.
Nervous system disorders Hypotonia	11.1% 1/9 • Week 260 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.
Psychiatric disorders Agitation	11.1% 1/9 • Week 260 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.
Reproductive system and breast disorders Penile blister	20.0% 1/5 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Cough	55.6% 5/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	22.2% 2/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Sneezing	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Tonsillar disorder	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Use of accessory respiratory muscles	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Wheezing	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Dermatitis diaper	44.4% 4/9 • Week 260 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.
Skin and subcutaneous tissue disorders Rash	33.3% 3/9 • Week 260 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.
Skin and subcutaneous tissue disorders Urticaria	33.3% 3/9 • Week 260 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.
Skin and subcutaneous tissue disorders Eczema	33.3% 3/9 • Week 260 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.
Skin and subcutaneous tissue disorders Pruritus generalised	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Umbilical erythema	11.1% 1/9 • Week 260 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.
Vascular disorders Hypotension	11.1% 1/9 • Week 260 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.
Vascular disorders Hypertension	11.1% 1/9 • Week 260 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.
Vascular disorders Pallor	11.1% 1/9 • Week 260 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.
Investigations Lymphocyte count increased	11.1% 1/9 • Week 260 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.
General disorders Asthenia	11.1% 1/9 • Week 260 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.
General disorders Catheter site pain	11.1% 1/9 • Week 260 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.
General disorders Catheter site swelling	11.1% 1/9 • Week 260 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.
General disorders Swelling	11.1% 1/9 • Week 260 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.
Psychiatric disorders Irritability	11.1% 1/9 • Week 260 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.
Psychiatric disorders Emotional disorder	11.1% 1/9 • Week 260 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.
Reproductive system and breast disorders Genital rash	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Fall	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Head injury	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Laceration	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Stoma site inflammation	11.1% 1/9 • Week 260 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.
Injury, poisoning and procedural complications Tooth injury	11.1% 1/9 • Week 260 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.
Investigations Lymphocyte count abnormal	11.1% 1/9 • Week 260 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.
Investigations Monocyte count increased	11.1% 1/9 • Week 260 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.
Investigations Adenovirus test positive	11.1% 1/9 • Week 260 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.
Investigations Blood immunoglobulin G decreased	11.1% 1/9 • Week 260 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.
Investigations Blood albumin decreased	22.2% 2/9 • Week 260 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.
Investigations Clostridium test positive	11.1% 1/9 • Week 260 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.
Investigations Parasite stool test positive	11.1% 1/9 • Week 260 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.
Investigations Pseudomonas test positive	11.1% 1/9 • Week 260 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.
Investigations Respirovirus test positive	11.1% 1/9 • Week 260 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.
Investigations Vitamin E decreased	11.1% 1/9 • Week 260 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.
Investigations Protein total decreased	22.2% 2/9 • Week 260 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.
Blood and lymphatic system disorders Lymphadenopathy	11.1% 1/9 • Week 260 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.
Blood and lymphatic system disorders Lymphopenia	11.1% 1/9 • Week 260 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.
Blood and lymphatic system disorders Iron deficiency anaemia	22.2% 2/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Respiratory distress	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Productive cough	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Tachypnoea	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	11.1% 1/9 • Week 260 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	22.2% 2/9 • Week 260 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.
Nervous system disorders Headache	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Abdominal discomfort	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Abdominal pain upper	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Abdominal pain	33.3% 3/9 • Week 260 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.
Gastrointestinal disorders Constipation	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Dental caries	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Enteritis	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Flatulence	11.1% 1/9 • Week 260 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.
Gastrointestinal disorders Gastritis	11.1% 1/9 • Week 260 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.
Renal and urinary disorders Dysuria	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Petechiae	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Pruritus	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Rash macular	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Skin discolouration	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Skin irritation	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Xanthoma	11.1% 1/9 • Week 260 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.
Skin and subcutaneous tissue disorders Erythema	22.2% 2/9 • Week 260 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.
Product Issues Device malfunction	11.1% 1/9 • Week 260 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.
Musculoskeletal and connective tissue disorders Myalgia	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Vitamin A deficiency	11.1% 1/9 • Week 260 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.
Metabolism and nutrition disorders Vitamin E deficiency	22.2% 2/9 • Week 260 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.
Metabolism and nutrition disorders Vitamin K deficiency	22.2% 2/9 • Week 260 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.
Infections and infestations Angular cheilitis	11.1% 1/9 • Week 260 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.
Infections and infestations Croup infectious	11.1% 1/9 • Week 260 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.
Infections and infestations Gastroenteritis viral	11.1% 1/9 • Week 260 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.
Infections and infestations Infectious mononucleosis	11.1% 1/9 • Week 260 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.
Infections and infestations Influenza	11.1% 1/9 • Week 260 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.
Infections and infestations Scarlet fever	11.1% 1/9 • Week 260 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.
Infections and infestations Stoma site candida	11.1% 1/9 • Week 260 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.
Infections and infestations Tonsillitis	11.1% 1/9 • Week 260 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.
Infections and infestations Fungal skin infection	22.2% 2/9 • Week 260 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.
Infections and infestations Hand-foot-and-mouth disease	22.2% 2/9 • Week 260 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.
Infections and infestations Urinary tract infection	22.2% 2/9 • Week 260 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.
Infections and infestations Ear infection	33.3% 3/9 • Week 260 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.
Infections and infestations Conjunctivitis	22.2% 2/9 • Week 260 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.

Additional Information

Alexion Pharmaceuticals Inc.

Alexion Pharmaceuticals Inc.

Phone: 855-752-2356

Email: clinicaltrials@alexion.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place