Cholesterol Ester Storage Disease (CESD), LAL-Deficiency, Lysosomal Acid Lipase Deficiency
Conditions
Keywords
Enzyme replacement therapy (ERT), Lysosomal storage disease, Late onset lysosomal acid lipase (LAL) deficiency, Acid cholesteryl ester hydrolase deficiency, type 2, Acid lipase disease, Cholesterol ester hydrolase deficiency, LAL deficiency, LIPA enzyme deficiency
Brief summary
This was an extension study to Study LAL-CL01 (NCT01307098). The primary objective of the study was to evaluate the long-term safety and tolerability of sebelipase alfa in participants with liver dysfunction due to lysosomal acid lipase (LAL) deficiency.
Detailed description
Participants who successfully received all 4 doses of sebelipase alfa in Study LAL-CL01 and opted to continue treatment in the extension study underwent screening assessments to determine study eligibility. Eligible participants initiated treatment in the extension study at least 4 weeks after their last dose of sebelipase alfa in Study LAL-CL01. This extension study consisted of a treatment period of up to 5 years, and a follow-up period of approximately 30 days after the last dose of sebelipase alfa. Cholesteryl ester storage disease (CESD) is the late onset phenotype for LAL deficiency, a lysosomal storage disorder, which also has an early onset phenotype that primarily affects infants. CESD can present in childhood but often goes unrecognized until adulthood when the underlying pathology is advanced. Many of the signs and symptoms are common to patients with other liver conditions. CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests (LFTs) and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some patients. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.
Interventions
DRUGsebelipase alfa
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant received all 4 scheduled doses of sebelipase alfa in Study LAL-CL01 with no life-threatening or unmanageable study drug toxicity.
Exclusion criteria
* Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances * Clinically significant abnormal values on laboratory screening tests, other than LFTs or lipid panel tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants Reporting TEAEs And IARs | From after first dose administration post-Baseline through EOS during study LAL-CL04 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline In Liver Volume | Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS | 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. |
| Changes From Baseline In Liver Fat Content | Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260 | 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. |
| Changes From Baseline In GGT And ALP | Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS | 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. |
| Changes From Baseline In ALT And AST | Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS | 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. |
| Changes From Baseline In Serum Ferritin | Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS | 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. |
| Changes From Baseline In Hs-CRP | Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS | 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. |
| Changes From Baseline In Serum Lipids | Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS | 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. |
Countries
Canada, Czechia, France, United Kingdom, United States
Participant flow
Pre-assignment details
9 participants who completed Study LAL-CL01 (received all 4 doses of sebelipase alfa) were screened for eligibility for enrollment in this extension study (LAL-CL04). 8 participants met all enrollment criteria and were enrolled. 1 participant who required a liver transplant no longer met the entry criteria.
Participants by arm
| Arm | Count |
|---|---|
| Open-Label Sebelipase Alfa 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. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Open-Label Sebelipase Alfa |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 30.3 years STANDARD_DEVIATION 10.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment Canada | 1 Participants |
| Region of Enrollment Czechia | 1 Participants |
| Region of Enrollment France | 1 Participants |
| Region of Enrollment United Kingdom | 2 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
Number Of Participants Reporting TEAEs And IARs
Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-associated reactions (IARs). The number of participants who discontinued from the study due to a TEAE is also presented. An IAR was defined as any adverse event that occurred during the 2-hour infusion or within 4 hours after the end of the infusion and was assessed by the investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. TEAEs that occurred after the first dose administration at Week 1 through the End of Study (EOS) are presented. End of study was 30 days (+ 7 days) after the last dose of study drug (at Week 260).
Time frame: From after first dose administration post-Baseline through EOS during study LAL-CL04
Population: Safety Analysis Set: All participants who received any amount of study drug in the extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open-Label Sebelipase Alfa | Number Of Participants Reporting TEAEs And IARs | TEAEs | 8 Participants |
| Open-Label Sebelipase Alfa | Number Of Participants Reporting TEAEs And IARs | Serious TEAEs | 1 Participants |
| Open-Label Sebelipase Alfa | Number Of Participants Reporting TEAEs And IARs | IARs | 2 Participants |
| Open-Label Sebelipase Alfa | Number Of Participants Reporting TEAEs And IARs | TEAEs Leading to Study Discontinuation | 0 Participants |
Secondary
Changes From Baseline In ALT And AST
Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time frame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | ALT Week 24 | -38.1 units (U)/liter (L) | Standard Deviation 24 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | ALT Week 52 | -40.6 units (U)/liter (L) | Standard Deviation 20.5 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | ALT Week 12 | -35.9 units (U)/liter (L) | Standard Deviation 19.99 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | ALT Week 104 | -42.5 units (U)/liter (L) | Standard Deviation 19.65 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | ALT Week 156 | -29.5 units (U)/liter (L) | Standard Deviation 20.38 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | ALT Week 208 | -26.7 units (U)/liter (L) | Standard Deviation 30.58 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | ALT Week 260 | -31.6 units (U)/liter (L) | Standard Deviation 21.78 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | ALT EOS | -26.6 units (U)/liter (L) | Standard Deviation 31.1 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | AST Week 12 | -13.9 units (U)/liter (L) | Standard Deviation 7.02 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | AST Week 24 | -12.4 units (U)/liter (L) | Standard Deviation 11.71 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | AST Week 52 | -18.6 units (U)/liter (L) | Standard Deviation 12.82 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | AST Week 104 | -11.8 units (U)/liter (L) | Standard Deviation 15.59 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | AST Week 156 | -12.8 units (U)/liter (L) | Standard Deviation 9.95 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | AST Week 208 | -10.4 units (U)/liter (L) | Standard Deviation 14.86 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | AST Week 260 | -10.8 units (U)/liter (L) | Standard Deviation 13.7 |
| Open-Label Sebelipase Alfa | Changes From Baseline In ALT And AST | AST EOS | -15.3 units (U)/liter (L) | Standard Deviation 14.27 |
Secondary
Changes From Baseline In GGT And ALP
Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for gamma glutamyltransferase (GGT) and alkaline phosphatase (ALP). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time frame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | GGT Week 24 | -13.8 U/L | Standard Deviation 24.63 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | GGT Week 52 | -14.0 U/L | Standard Deviation 18.89 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | ALP Week 24 | -18.3 U/L | Standard Deviation 20.74 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | ALP Week 52 | -12.4 U/L | Standard Deviation 18.78 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | ALP EOS | -7.9 U/L | Standard Deviation 20.82 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | GGT Week 12 | -13.6 U/L | Standard Deviation 28.79 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | GGT Week 104 | -22.4 U/L | Standard Deviation 34.01 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | GGT Week 156 | 0.1 U/L | Standard Deviation 11.32 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | GGT Week 208 | 2.3 U/L | Standard Deviation 10.13 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | GGT Week 260 | -6.0 U/L | Standard Deviation 12.33 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | GGT EOS | -4.0 U/L | Standard Deviation 7.7 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | ALP Week 12 | -15.3 U/L | Standard Deviation 12.09 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | ALP Week 104 | -18.0 U/L | Standard Deviation 9.68 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | ALP Week 156 | -6.4 U/L | Standard Deviation 11.81 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | ALP Week 208 | -5.9 U/L | Standard Deviation 16.6 |
| Open-Label Sebelipase Alfa | Changes From Baseline In GGT And ALP | ALP Week 260 | -14.2 U/L | Standard Deviation 21.32 |
Secondary
Changes From Baseline In Hs-CRP
Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for high sensitivity C-reactive protein (hs-CRP). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time frame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Sebelipase Alfa | Changes From Baseline In Hs-CRP | Week 12 | -1.41 mg/L | Standard Deviation 3.022 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Hs-CRP | Week 24 | -1.03 mg/L | Standard Deviation 3.945 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Hs-CRP | Week 52 | -1.40 mg/L | Standard Deviation 3.245 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Hs-CRP | Week 104 | -1.50 mg/L | Standard Deviation 4.079 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Hs-CRP | Week 156 | -1.09 mg/L | Standard Deviation 3.323 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Hs-CRP | Week 208 | -1.34 mg/L | Standard Deviation 3.674 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Hs-CRP | Week 260 | -0.16 mg/L | Standard Deviation 0.619 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Hs-CRP | EOS | -1.33 mg/L | Standard Deviation 2.985 |
Secondary
Changes From Baseline In Liver Fat Content
Changes in liver fat content from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260, as assessed by multi-echo gradient-echo MRI. Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time frame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Fat Content | Week 10 or 12 | -2.816 percentage fat fraction | Standard Deviation 1.8025 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Fat Content | Week 24 | -2.772 percentage fat fraction | Standard Deviation 3.0024 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Fat Content | Week 52 | -3.633 percentage fat fraction | Standard Deviation 2.5736 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Fat Content | Week 104 | -4.348 percentage fat fraction | Standard Deviation 2.4486 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Fat Content | Week 156 | -3.953 percentage fat fraction | Standard Deviation 4.1182 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Fat Content | Week 208 | -4.007 percentage fat fraction | Standard Deviation 3.426 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Fat Content | Week 260 | -0.060 percentage fat fraction | Standard Deviation 3.4507 |
Secondary
Changes From Baseline In Liver Volume
Changes in liver volume from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS was assessed by magnetic resonance imaging (MRI). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04. Liver volume was expressed as multiples of normal (MN), where normal is defined as 2.5% of body weight.
Time frame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Volume | EOS | -0.205 Multiples of Normal (MN) | Standard Deviation 0.0358 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Volume | Week 10 or 12 | -0.096 Multiples of Normal (MN) | Standard Deviation 0.0892 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Volume | Week 24 | -0.099 Multiples of Normal (MN) | Standard Deviation 0.1513 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Volume | Week 52 | -0.096 Multiples of Normal (MN) | Standard Deviation 0.0641 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Volume | Week 104 | -0.176 Multiples of Normal (MN) | Standard Deviation 0.0801 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Volume | Week 156 | -0.082 Multiples of Normal (MN) | Standard Deviation 0.0732 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Volume | Week 208 | -0.182 Multiples of Normal (MN) | Standard Deviation 0.0556 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Liver Volume | Week 260 | -0.218 Multiples of Normal (MN) | Standard Deviation 0.0388 |
Secondary
Changes From Baseline In Serum Ferritin
Changes from Baseline to Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS for serum ferritin. Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time frame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Ferritin | Week 12 | -37.0 microgram (µg)/L | Standard Deviation 29.93 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Ferritin | Week 24 | -40.1 microgram (µg)/L | Standard Deviation 47.27 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Ferritin | Week 52 | -18.1 microgram (µg)/L | Standard Deviation 32.68 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Ferritin | Week 104 | -22.8 microgram (µg)/L | Standard Deviation 44.57 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Ferritin | Week 156 | 0.0 microgram (µg)/L | Standard Deviation 34.5 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Ferritin | Week 208 | 18.0 microgram (µg)/L | Standard Deviation 40.41 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Ferritin | Week 260 | 63.0 microgram (µg)/L | Standard Deviation 70.53 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Ferritin | EOS | 47.7 microgram (µg)/L | Standard Deviation 56.06 |
Secondary
Changes From Baseline In Serum Lipids
Lipid changes from Baseline to Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS were measured in serum for total cholesterol (Total-C), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Baseline values were defined as the last measurement prior to the first infusion of sebelipase alfa in Study LAL-CL04.
Time frame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | Total-C Week 12 | -34.5 mg/dL | Standard Deviation 40.5 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | Total-C Week 24 | -59.3 mg/dL | Standard Deviation 38.83 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | Total-C Week 52 | -73.9 mg/dL | Standard Deviation 54.43 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | Total-C Week 104 | -60.8 mg/dL | Standard Deviation 50.82 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | Total-C Week 156 | -36.4 mg/dL | Standard Deviation 43.9 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | Total-C Week 208 | 1.1 mg/dL | Standard Deviation 93.21 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | Total-C Week 260 | -45.5 mg/dL | Standard Deviation 50.85 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | Total-C EOS | -21.9 mg/dL | Standard Deviation 59.89 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | HDL-C Week 12 | 4.9 mg/dL | Standard Deviation 3.95 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | HDL-C Week 24 | 5.7 mg/dL | Standard Deviation 6.19 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | HDL-C Week 52 | 9.0 mg/dL | Standard Deviation 7.25 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | HDL-C Week 104 | 6.5 mg/dL | Standard Deviation 9.04 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | HDL-C Week 156 | 5.2 mg/dL | Standard Deviation 9.5 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | HDL-C Week 208 | 4.9 mg/dL | Standard Deviation 4.91 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | HDL-C Week 260 | 3.4 mg/dL | Standard Deviation 8.96 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | HDL-C EOS | 6.7 mg/dL | Standard Deviation 9.02 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | LDL-C Week 12 | -34.1 mg/dL | Standard Deviation 37.54 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | LDL-C Week 24 | -68.5 mg/dL | Standard Deviation 40.22 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | LDL-C Week 52 | -78.5 mg/dL | Standard Deviation 50.91 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | LDL-C Week 104 | -68.7 mg/dL | Standard Deviation 43.11 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | LDL-C Week 156 | -40.8 mg/dL | Standard Deviation 38.91 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | LDL-C Week 208 | -20.5 mg/dL | Standard Deviation 66.41 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | LDL-C Week 260 | -43.4 mg/dL | Standard Deviation 44.05 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | LDL-C EOS | -35.0 mg/dL | Standard Deviation 42.27 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | TG Week 12 | -18.5 mg/dL | Standard Deviation 71.93 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | TG Week 24 | -17.5 mg/dL | Standard Deviation 37.62 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | TG Week 52 | -45.2 mg/dL | Standard Deviation 66.91 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | TG Week 104 | -24.0 mg/dL | Standard Deviation 84.25 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | TG Week 156 | -11.2 mg/dL | Standard Deviation 60.45 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | TG Week 208 | 5.6 mg/dL | Standard Deviation 94.18 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | TG Week 260 | -4.8 mg/dL | Standard Deviation 66.03 |
| Open-Label Sebelipase Alfa | Changes From Baseline In Serum Lipids | TG EOS | 15.7 mg/dL | Standard Deviation 106.54 |