Trial Outcomes & Findings for Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency (NCT NCT01488097)

Last Updated: 2018-07-20

Results Overview

Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-associated reactions (IARs). The number of participants who discontinued from the study due to a TEAE is also presented. An IAR was defined as any adverse event that occurred during the 2-hour infusion or within 4 hours after the end of the infusion and was assessed by the investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. TEAEs that occurred after the first dose administration at Week 1 through the End of Study (EOS) are presented. End of study was 30 days (+ 7 days) after the last dose of study drug (at Week 260).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

From after first dose administration post-Baseline through EOS during study LAL-CL04

Results posted on

2018-07-20

Participant Flow

9 participants who completed Study LAL-CL01 (received all 4 doses of sebelipase alfa) were screened for eligibility for enrollment in this extension study (LAL-CL04). 8 participants met all enrollment criteria and were enrolled. 1 participant who required a liver transplant no longer met the entry criteria.

Participant milestones

Participant milestones
Measure	Open-Label Sebelipase Alfa Participants were administered sebelipase alfa once weekly (qw) as an intravenous (IV) infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 milligrams per kilogram \[mg/kg\]) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing every other week (qow) at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Study STARTED	8
Overall Study Received Study Drug in Extension Study	8
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-Label Sebelipase Alfa Participants were administered sebelipase alfa once weekly (qw) as an intravenous (IV) infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 milligrams per kilogram \[mg/kg\]) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing every other week (qow) at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Overall Study Lost to Follow-up	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	30.3 years STANDARD_DEVIATION 10.69 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 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	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Canada	1 Participants n=5 Participants
Region of Enrollment Czechia	1 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants
Region of Enrollment United Kingdom	2 Participants n=5 Participants
Region of Enrollment France	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From after first dose administration post-Baseline through EOS during study LAL-CL04

Population: Safety Analysis Set: All participants who received any amount of study drug in the extension study.

Outcome measures

Outcome measures
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Number Of Participants Reporting TEAEs And IARs TEAEs	8 Participants
Number Of Participants Reporting TEAEs And IARs Serious TEAEs	1 Participants
Number Of Participants Reporting TEAEs And IARs IARs	2 Participants
Number Of Participants Reporting TEAEs And IARs TEAEs Leading to Study Discontinuation	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

Population: Participants in the Full Analysis Set (FAS) for whom ALT and AST data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.

Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

Outcome measures

Outcome measures
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Changes From Baseline In ALT And AST ALT Week 12	-35.9 units (U)/liter (L) Standard Deviation 19.99
Changes From Baseline In ALT And AST ALT Week 24	-38.1 units (U)/liter (L) Standard Deviation 24.00
Changes From Baseline In ALT And AST ALT Week 52	-40.6 units (U)/liter (L) Standard Deviation 20.50
Changes From Baseline In ALT And AST ALT Week 104	-42.5 units (U)/liter (L) Standard Deviation 19.65
Changes From Baseline In ALT And AST ALT Week 156	-29.5 units (U)/liter (L) Standard Deviation 20.38
Changes From Baseline In ALT And AST ALT Week 208	-26.7 units (U)/liter (L) Standard Deviation 30.58
Changes From Baseline In ALT And AST ALT Week 260	-31.6 units (U)/liter (L) Standard Deviation 21.78
Changes From Baseline In ALT And AST ALT EOS	-26.6 units (U)/liter (L) Standard Deviation 31.10
Changes From Baseline In ALT And AST AST Week 12	-13.9 units (U)/liter (L) Standard Deviation 7.02
Changes From Baseline In ALT And AST AST Week 24	-12.4 units (U)/liter (L) Standard Deviation 11.71
Changes From Baseline In ALT And AST AST Week 52	-18.6 units (U)/liter (L) Standard Deviation 12.82
Changes From Baseline In ALT And AST AST Week 104	-11.8 units (U)/liter (L) Standard Deviation 15.59
Changes From Baseline In ALT And AST AST Week 156	-12.8 units (U)/liter (L) Standard Deviation 9.95
Changes From Baseline In ALT And AST AST Week 208	-10.4 units (U)/liter (L) Standard Deviation 14.86
Changes From Baseline In ALT And AST AST Week 260	-10.8 units (U)/liter (L) Standard Deviation 13.70
Changes From Baseline In ALT And AST AST EOS	-15.3 units (U)/liter (L) Standard Deviation 14.27

SECONDARY outcome

Timeframe: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

Population: Participants in the FAS for whom liver volume data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.

Changes in liver volume from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS was assessed by magnetic resonance imaging (MRI). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04. Liver volume was expressed as multiples of normal (MN), where normal is defined as 2.5% of body weight.

Outcome measures

Outcome measures
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Changes From Baseline In Liver Volume Week 10 or 12	-0.096 Multiples of Normal (MN) Standard Deviation 0.0892
Changes From Baseline In Liver Volume Week 24	-0.099 Multiples of Normal (MN) Standard Deviation 0.1513
Changes From Baseline In Liver Volume Week 52	-0.096 Multiples of Normal (MN) Standard Deviation 0.0641
Changes From Baseline In Liver Volume Week 104	-0.176 Multiples of Normal (MN) Standard Deviation 0.0801
Changes From Baseline In Liver Volume Week 156	-0.082 Multiples of Normal (MN) Standard Deviation 0.0732
Changes From Baseline In Liver Volume Week 208	-0.182 Multiples of Normal (MN) Standard Deviation 0.0556
Changes From Baseline In Liver Volume Week 260	-0.218 Multiples of Normal (MN) Standard Deviation 0.0388
Changes From Baseline In Liver Volume EOS	-0.205 Multiples of Normal (MN) Standard Deviation 0.0358

SECONDARY outcome

Timeframe: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260

Population: Participants in the FAS for whom liver fat content data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.

Changes in liver fat content from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260, as assessed by multi-echo gradient-echo MRI. Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

Outcome measures

Outcome measures
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Changes From Baseline In Liver Fat Content Week 10 or 12	-2.816 percentage fat fraction Standard Deviation 1.8025
Changes From Baseline In Liver Fat Content Week 24	-2.772 percentage fat fraction Standard Deviation 3.0024
Changes From Baseline In Liver Fat Content Week 52	-3.633 percentage fat fraction Standard Deviation 2.5736
Changes From Baseline In Liver Fat Content Week 104	-4.348 percentage fat fraction Standard Deviation 2.4486
Changes From Baseline In Liver Fat Content Week 156	-3.953 percentage fat fraction Standard Deviation 4.1182
Changes From Baseline In Liver Fat Content Week 208	-4.007 percentage fat fraction Standard Deviation 3.4260
Changes From Baseline In Liver Fat Content Week 260	-0.060 percentage fat fraction Standard Deviation 3.4507

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

Population: Participants in the FAS for whom GGT and ALP data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.

Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for gamma glutamyltransferase (GGT) and alkaline phosphatase (ALP). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

Outcome measures

Outcome measures
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Changes From Baseline In GGT And ALP GGT Week 12	-13.6 U/L Standard Deviation 28.79
Changes From Baseline In GGT And ALP GGT Week 24	-13.8 U/L Standard Deviation 24.63
Changes From Baseline In GGT And ALP GGT Week 52	-14.0 U/L Standard Deviation 18.89
Changes From Baseline In GGT And ALP GGT Week 104	-22.4 U/L Standard Deviation 34.01
Changes From Baseline In GGT And ALP GGT Week 156	0.1 U/L Standard Deviation 11.32
Changes From Baseline In GGT And ALP GGT Week 208	2.3 U/L Standard Deviation 10.13
Changes From Baseline In GGT And ALP GGT Week 260	-6.0 U/L Standard Deviation 12.33
Changes From Baseline In GGT And ALP GGT EOS	-4.0 U/L Standard Deviation 7.70
Changes From Baseline In GGT And ALP ALP Week 12	-15.3 U/L Standard Deviation 12.09
Changes From Baseline In GGT And ALP ALP Week 24	-18.3 U/L Standard Deviation 20.74
Changes From Baseline In GGT And ALP ALP Week 52	-12.4 U/L Standard Deviation 18.78
Changes From Baseline In GGT And ALP ALP Week 104	-18.0 U/L Standard Deviation 9.68
Changes From Baseline In GGT And ALP ALP Week 156	-6.4 U/L Standard Deviation 11.81
Changes From Baseline In GGT And ALP ALP Week 208	-5.9 U/L Standard Deviation 16.60
Changes From Baseline In GGT And ALP ALP Week 260	-14.2 U/L Standard Deviation 21.32
Changes From Baseline In GGT And ALP ALP EOS	-7.9 U/L Standard Deviation 20.82

SECONDARY outcome

Timeframe: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

Population: Participants in the FAS for whom lipid data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.

Lipid changes from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS were measured in serum for total cholesterol (Total-C), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

Outcome measures

Outcome measures
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Changes From Baseline In Serum Lipids Total-C Week 12	-34.5 mg/dL Standard Deviation 40.50
Changes From Baseline In Serum Lipids Total-C Week 24	-59.3 mg/dL Standard Deviation 38.83
Changes From Baseline In Serum Lipids Total-C Week 52	-73.9 mg/dL Standard Deviation 54.43
Changes From Baseline In Serum Lipids Total-C Week 104	-60.8 mg/dL Standard Deviation 50.82
Changes From Baseline In Serum Lipids Total-C Week 156	-36.4 mg/dL Standard Deviation 43.90
Changes From Baseline In Serum Lipids Total-C Week 208	1.1 mg/dL Standard Deviation 93.21
Changes From Baseline In Serum Lipids Total-C Week 260	-45.5 mg/dL Standard Deviation 50.85
Changes From Baseline In Serum Lipids Total-C EOS	-21.9 mg/dL Standard Deviation 59.89
Changes From Baseline In Serum Lipids HDL-C Week 12	4.9 mg/dL Standard Deviation 3.95
Changes From Baseline In Serum Lipids HDL-C Week 24	5.7 mg/dL Standard Deviation 6.19
Changes From Baseline In Serum Lipids HDL-C Week 52	9.0 mg/dL Standard Deviation 7.25
Changes From Baseline In Serum Lipids HDL-C Week 104	6.5 mg/dL Standard Deviation 9.04
Changes From Baseline In Serum Lipids HDL-C Week 156	5.2 mg/dL Standard Deviation 9.50
Changes From Baseline In Serum Lipids HDL-C Week 208	4.9 mg/dL Standard Deviation 4.91
Changes From Baseline In Serum Lipids HDL-C Week 260	3.4 mg/dL Standard Deviation 8.96
Changes From Baseline In Serum Lipids HDL-C EOS	6.7 mg/dL Standard Deviation 9.02
Changes From Baseline In Serum Lipids LDL-C Week 12	-34.1 mg/dL Standard Deviation 37.54
Changes From Baseline In Serum Lipids LDL-C Week 24	-68.5 mg/dL Standard Deviation 40.22
Changes From Baseline In Serum Lipids LDL-C Week 52	-78.5 mg/dL Standard Deviation 50.91
Changes From Baseline In Serum Lipids LDL-C Week 104	-68.7 mg/dL Standard Deviation 43.11
Changes From Baseline In Serum Lipids LDL-C Week 156	-40.8 mg/dL Standard Deviation 38.91
Changes From Baseline In Serum Lipids LDL-C Week 208	-20.5 mg/dL Standard Deviation 66.41
Changes From Baseline In Serum Lipids LDL-C Week 260	-43.4 mg/dL Standard Deviation 44.05
Changes From Baseline In Serum Lipids LDL-C EOS	-35.0 mg/dL Standard Deviation 42.27
Changes From Baseline In Serum Lipids TG Week 12	-18.5 mg/dL Standard Deviation 71.93
Changes From Baseline In Serum Lipids TG Week 24	-17.5 mg/dL Standard Deviation 37.62
Changes From Baseline In Serum Lipids TG Week 52	-45.2 mg/dL Standard Deviation 66.91
Changes From Baseline In Serum Lipids TG Week 104	-24.0 mg/dL Standard Deviation 84.25
Changes From Baseline In Serum Lipids TG Week 156	-11.2 mg/dL Standard Deviation 60.45
Changes From Baseline In Serum Lipids TG Week 208	5.6 mg/dL Standard Deviation 94.18
Changes From Baseline In Serum Lipids TG Week 260	-4.8 mg/dL Standard Deviation 66.03
Changes From Baseline In Serum Lipids TG EOS	15.7 mg/dL Standard Deviation 106.54

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

Population: Participants in the FAS for whom serum ferritin data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.

Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for serum ferritin. Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

Outcome measures

Outcome measures
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Changes From Baseline In Serum Ferritin Week 12	-37.0 microgram (µg)/L Standard Deviation 29.93
Changes From Baseline In Serum Ferritin Week 24	-40.1 microgram (µg)/L Standard Deviation 47.27
Changes From Baseline In Serum Ferritin Week 52	-18.1 microgram (µg)/L Standard Deviation 32.68
Changes From Baseline In Serum Ferritin Week 104	-22.8 microgram (µg)/L Standard Deviation 44.57
Changes From Baseline In Serum Ferritin Week 156	0.0 microgram (µg)/L Standard Deviation 34.50
Changes From Baseline In Serum Ferritin Week 208	18.0 microgram (µg)/L Standard Deviation 40.41
Changes From Baseline In Serum Ferritin Week 260	63.0 microgram (µg)/L Standard Deviation 70.53
Changes From Baseline In Serum Ferritin EOS	47.7 microgram (µg)/L Standard Deviation 56.06

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

Population: Participants in the FAS for whom hs-CRP data were available at both Baseline and the indicated post-treatment time point. The FAS included all participants who received at least 1 complete infusion of sebelipase alfa in this study and who had at least 1 post-treatment measurement in this study.

Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for high sensitivity C-reactive protein (hs-CRP). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.

Outcome measures

Outcome measures
Measure	Open-Label Sebelipase Alfa n=8 Participants Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing qow at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Changes From Baseline In Hs-CRP Week 12	-1.41 mg/L Standard Deviation 3.022
Changes From Baseline In Hs-CRP Week 24	-1.03 mg/L Standard Deviation 3.945
Changes From Baseline In Hs-CRP Week 52	-1.40 mg/L Standard Deviation 3.245
Changes From Baseline In Hs-CRP Week 104	-1.50 mg/L Standard Deviation 4.079
Changes From Baseline In Hs-CRP Week 156	-1.09 mg/L Standard Deviation 3.323
Changes From Baseline In Hs-CRP Week 208	-1.34 mg/L Standard Deviation 3.674
Changes From Baseline In Hs-CRP Week 260	-0.16 mg/L Standard Deviation 0.619
Changes From Baseline In Hs-CRP EOS	-1.33 mg/L Standard Deviation 2.985

Adverse Events

Open-Label Sebelipase Alfa

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open-Label Sebelipase Alfa n=8 participants at risk Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to qow dosing at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Hepatobiliary disorders Cholecystitis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Hepatobiliary disorders Cholelithiasis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.

Other adverse events

Other adverse events
Measure	Open-Label Sebelipase Alfa n=8 participants at risk Participants were administered sebelipase alfa qw as an IV infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 mg/kg) for 4 weeks. After the initial 4 qw doses, participants transitioned to qow dosing at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.
Cardiac disorders Bradycardia	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Cardiac disorders Palpitations	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Cardiac disorders Tachycardia	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Ear and labyrinth disorders Ear pain	37.5% 3/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Eye disorders Blepharitis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Eye disorders Conjunctivitis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Eye disorders Dry eye	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Eye disorders Eye pain	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Eye disorders Keratitis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Eye disorders Occular hyperaemia	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Eye disorders Vision blurred	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Abdominal distension	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Abdominal pain	62.5% 5/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Abdominal pain upper	37.5% 3/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Diarrhoea	50.0% 4/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Dyspepsia	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Faeces soft	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Flatulence	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Gastrooesophageal reflux disease	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Malocclusion	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Nausea	62.5% 5/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Toothache	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Gastrointestinal disorders Vomiting	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
General disorders Catheter site pain	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
General disorders Chest discomfort	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
General disorders Chest pain	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
General disorders Chills	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
General disorders Fatigue	37.5% 3/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
General disorders Non-cardiac chest pain	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
General disorders Pain	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
General disorders Pyrexia	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Hepatobiliary disorders Bile duct stone	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Hepatobiliary disorders Cholelithiasis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Hepatobiliary disorders Granulomatous liver disease	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Hepatobiliary disorders Hepatic pain	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Immune system disorders Hypersensitivity	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Immune system disorders Seasonal allergy	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Abscess limb	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Bacterial vaginosis	50.0% 1/2 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Cellulitis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Ear infection	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Ear lobe infection	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Eye infection	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Folliculitis	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Fungal skin infection	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Gastroenteritis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Infected dermal cyst	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Influenza	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Lower respiratory tract infection	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Nasopharyngitis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Pharyngitis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Rash pustular	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Rhinitis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Subcutaneous abscess	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Upper respiratory tract infection	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Urinary tract infection	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Infections and infestations Viral upper respiratory tract infection	62.5% 5/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Injury, poisoning and procedural complications Arthropod bite	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Injury, poisoning and procedural complications Cartilage injury	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Injury, poisoning and procedural complications Iliotibial band syndrome	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Injury, poisoning and procedural complications Laceration	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Injury, poisoning and procedural complications Post procedural haemorrhage	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Injury, poisoning and procedural complications Procedural pain	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Injury, poisoning and procedural complications Procedural dizziness	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Injury, poisoning and procedural complications Sunburn	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations Activated partial thromboplastin time prolonged	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations Blood creatinine increased	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations C-reactive protein increased	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations Eosinophil count increased	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations Low density lipoprotein increased	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations Lymphocyte count increased	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations Mean cell volume increased	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations Prothrombin time abnormal	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations Vitamin B12 decreased	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Investigations White blood cell count increased	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Metabolism and nutrition disorders Decreased appetite	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Metabolism and nutrition disorders Vitamin D deficiency	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Back pain	50.0% 4/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Bone pain	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Limb mass	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Muscle spasms	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Muscle twitching	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Muscular weakness	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	37.5% 3/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Myalgia	37.5% 3/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Neck mass	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Pain in extremity	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Musculoskeletal and connective tissue disorders Spinal pain	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oral neoplasm benign	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Amnesia	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Clonic convulsion	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Dizziness	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Dysarthria	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Dyskinesia	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Headache	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Lethargy	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Paraesthesia	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Syncope	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Nervous system disorders Tremor	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Psychiatric disorders Depression	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Respiratory, thoracic and mediastinal disorders Choking	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Respiratory, thoracic and mediastinal disorders Cough	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	37.5% 3/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	25.0% 2/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Acne	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Dermal cyst	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Dermatitis acneiform	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Eczema	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Ephelides	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Pigmentation disorder	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Pruritus	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Rash macular	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Skin lesion	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Skin and subcutaneous tissue disorders Skin mass	37.5% 3/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Vascular disorders Flushing	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Vascular disorders Hyperaemia	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Vascular disorders Hypertension	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.
Vascular disorders Orthostatic hypotension	12.5% 1/8 • From after first dose administration post-Baseline through EOS during study LAL-CL04 Adverse events were obtained through participant reporting or were elicited by specific questioning or examination of the participant.

Additional Information

Alexion Pharmaceuticals Inc.

Phone: 475-230-2596

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place