A Multicenter Study of SBC-102 (Sebelipase Alfa) in Patients With Lysosomal Acid Lipase Deficiency/ ARISE (Acid Lipase Replacement Investigating Safety and Efficacy)
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ClinicalTrials.gov Identifier: NCT01757184 |
Recruitment Status
:
Active, not recruiting
First Posted
: December 28, 2012
Results First Posted
: April 18, 2016
Last Update Posted
: March 20, 2017
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This Phase 3 study will evaluate the efficacy and safety of 1 mg/kg IV infusions of SBC-102 (sebelipase alfa) administered every other week in patients with late onset lysosomal acid lipase (LAL) deficiency (cholesteryl ester storage disease).
Late onset LAL Deficiency is an underappreciated cause of cirrhosis, liver failure and dyslipidemia. There is currently no standard treatment for LAL Deficiency other than supportive care. Enzyme replacement therapy (ERT) may be a potential new treatment option for LAL Deficiency patients.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Cholesterol Ester Storage Disease (CESD) Lysosomal Acid Lipase Deficiency | Drug: SBC-102 [sebelipase alfa] (1 mg/kg) Drug: Placebo | Phase 3 |
Lysosomal Acid Lipase Deficiency (LALD) is a genetic disease which is characterized by abnormal lipid accumulation in many parts of the body due to a marked decrease in activity of the enzyme lysosomal acid lipase (LAL). Although a single disease, LALD presents with two major forms: early onset and late onset. Early onset LALD, also known as Wolman Disease, is characterized by severe malabsorption, growth failure, and hepatic failure and is usually fatal within the first year of life.
The late onset form of the disease, also known as Cholesteryl Ester Storage Disease (CESD), occurs in both children and adults and is an under-appreciated cause of fatty liver with prominent microvesicular steatosis and cirrhosis. Although the natural history of the disease has not been well studied, serious liver complications are frequently described including early death and liver transplantation. Other complications includes premature atherosclerosis (hardening of arteries) associated with high levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, often called the "bad" cholesterol. The levels of triglycerides can also be high and the levels of high-density lipoprotein (HDL) cholesterol (the "good" cholesterol) are typically low.
Current treatments mainly focus on control of the lipid abnormalities through diet and the use of lipid lowering medications. New treatments are needed for patients with LALD as current treatments only address some aspects of the disease and disease progression to cirrhosis still occurs. In pre-clinical studies and studies in patients with LALD, treatment with SBC-102 (sebelipase alfa) has been shown to produce improvements in markers of liver damage and in the lipid abnormalities. The purpose of this study is to examine the effects of using SBC-102 to treat late onset LALD (CESD) through a placebo-controlled, randomized, double-blinded study in both affected children and adults.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 66 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Multicenter, Randomized, Placebo-Controlled Study of SBC-102 in Patients With Lysosomal Acid Lipase Deficiency |
Study Start Date : | January 2013 |
Estimated Primary Completion Date : | January 2019 |
Estimated Study Completion Date : | January 2019 |

Arm | Intervention/treatment |
---|---|
Experimental: SBC-102 [sebelipase alfa]
Every other week IV infusions of SBC-102
|
Drug: SBC-102 [sebelipase alfa] (1 mg/kg) |
Placebo Comparator: Placebo
Every other week infusions of placebo
|
Drug: Placebo |
- Percentage of Subjects Achieving Alanine Aminotransferase (ALT) Normalization [ Time Frame: Baseline to the end of the double-blind period (week 20) ]The primary efficacy endpoint was the percentage of subjects who achieve alanine aminotransferase (ALT) normalization (i.e., ALT below the age- and gender-specific upper limit of normal provided by the central laboratory performing the assay) at the end of the double-blind treatment period (i.e., the last double-blind assessment), relative to placebo.
- Percentage Change From Baseline in LDL-c [ Time Frame: Baseline to the end of the double-blind period (week 20) ]Relative reduction (percentage change from baseline) in LDL-c at the end of the double-blind period.
- Percentage Change From Baseline in Non-HDL-c [ Time Frame: Baseline to the end of the double-blind period (week 20) ]Relative reduction (percentage change from baseline) in non-high density lipoprotein cholesterol (non-HDL-c) at the end of the double-blind period
- Percentage of Subjects Achieving Aspartate Aminotransferase (AST) Normalization [ Time Frame: Baseline to the end of the double-blind period (week 20) ]The percentage of subjects with an abnormal baseline aspartate aminotransferase (AST; i.e., >ULN) who achieved AST normalization, based on age- and gender-specific normal ranges provided by the central laboratory performing the assay.
- Percentage Change From Baseline in Triglycerides [ Time Frame: Baseline to the end of the double-blind period (week 20) ]Relative reduction (percentage change from baseline) in triglycerides at the end of the double-blind period
- Percentage Change From Baseline in HDL-c [ Time Frame: Baseline to the end of the double-blind period (week 20) ]Relative increase (percentage change from baseline) in high density lipoprotein cholesterol (HDL-c) at the end of the double-blind period
- Percentage Change From Baseline in Liver Fat Content [ Time Frame: Baseline to the end of the double-blind period (week 20) ]Decrease in liver fat content, as assessed by magnetic resonance imaging (MRI), in the subset of subjects for whom imaging was performed
- Number of Subjects With Improvement in Liver Histology (Decrease of >5% in Hepatic Steatosis Score) [ Time Frame: Baseline to the end of the double-blind period (week 20) ]The number of subjects who had an improvement in hepatic histology (i.e., a decrease of >5% in hepatic steatosis score) from baseline to Week 20, as determined by blinded central review, in the subset of subjects for whom liver biopsy was performed.
- Percentage Change From Baseline in Liver Volume [ Time Frame: Baseline to the end of the double-blind period (week 20) ]Relative reduction (percentage change from baseline) in liver volume, as assessed by magnetic resonance imaging, in the subset of subjects for whom imaging was performed

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Ages Eligible for Study: | 4 Years and older (Child, Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Subject and/or subject's parent or legal guardian provides informed consent
- Subject is ≥4 years of age
- Deficiency of LAL enzyme activity confirmed by dried blood spot (DBS) testing at screening
- ALT ≥1.5x ULN
- Female subjects of childbearing potential must not be pregnant or breastfeeding
- Subjects receiving lipid-lowering therapies must be on a stable dose of the medication
- Subjects receiving medications for the treatment of non-alcoholic fatty liver disease must be on a stable dose
Exclusion Criteria:
- Severe hepatic dysfunction (Child-Pugh Class C)
- Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
- Previous hematopoietic or liver transplant procedure
- Received treatment with high-dose corticosteroids (acute or chronic) within 26 weeks. (Note: Subjects receiving maintenance therapy with low-dose oral, intranasal, topical, or inhaled corticosteroids are considered eligible for the study)
- Known hypersensitivity to eggs
- Participated in a study employing an investigational medicinal product within 4 weeks prior to randomization

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01757184

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Alexion Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT01757184 History of Changes |
Other Study ID Numbers: |
LAL-CL02 |
First Posted: | December 28, 2012 Key Record Dates |
Results First Posted: | April 18, 2016 |
Last Update Posted: | March 20, 2017 |
Last Verified: | February 2017 |
Keywords provided by Alexion Pharmaceuticals:
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 Deficiency Wolman disease |
Additional relevant MeSH terms:
Wolman Disease Cholesterol Ester Storage Disease Lipidoses Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors |
Genetic Diseases, Inborn Lysosomal Storage Diseases Infant, Newborn, Diseases Lipid Metabolism Disorders Metabolic Diseases |