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A Multicenter Study of SBC-102 (Sebelipase Alfa) in Patients With Lysosomal Acid Lipase Deficiency/ ARISE (Acid Lipase Replacement Investigating Safety and Efficacy)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Alexion Pharmaceuticals Identifier:
First received: December 17, 2012
Last updated: February 13, 2017
Last verified: February 2017

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 Intervention Phase
Cholesterol Ester Storage Disease (CESD)
Lysosomal Acid Lipase Deficiency
Drug: SBC-102 [sebelipase alfa] (1 mg/kg)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Alexion Pharmaceuticals:

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • 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

Enrollment: 66
Study Start Date: January 2013
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.


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
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Please refer to this study by its identifier: NCT01757184

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United States, Arizona
Tucson, Arizona, United States
United States, California
Palo Alto, California, United States
San Francisco, California, United States
United States, Delaware
Wilmington, Delaware, United States
United States, Florida
Miami, Florida, United States
United States, Illinois
Chicago, Illinois, United States
United States, Massachusetts
Boston, Massachusetts, United States
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Buffalo, New York, United States
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New York, New York, United States
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Cincinnati, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Córdoba, Córdoba Province, Argentina
Australia, Victoria
Parkville, Victoria, Australia
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Newcastle, Australia
Perth, Australia
Porto Alegre, Rio Grande do Sul, Brazil
Monte Alegre, São Paulo, Brazil
Canada, Nova Scotia
Halifax, Nova Scotia, Canada
Canada, Quebec
Montréal, Quebec, Canada
Zagreb, Croatia
Czech Republic
Olomouc, Czech Republic
Prague, Czech Republic
Paris Cedex 15, France
Vandoeuvre les Nancy, France
Freiburg, Germany
Mainz, Germany
Munich, Germany
Athens, Greece
Jerusalem, Israel
Bergamo, Italy
Genoa, Italy
Padova, Italy
Rome, Italy
Turin, Italy
Tokyo, Japan
Tottori, Japan
Mexico City, Mexico
Krakow, Poland
Warszawa, Poland
Russian Federation
Moscow, Russian Federation
Albacete, Spain
Barcelona, Spain
Elche, Spain
Madrid, Spain
Oviedo, Spain
Ankara, Turkey
Izmir, Turkey
United Kingdom
Edgbaston, Birmingham, United Kingdom
Cambridge, United Kingdom
London, United Kingdom
Plymouth, United Kingdom
Salford, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Alexion Pharmaceuticals Identifier: NCT01757184     History of Changes
Other Study ID Numbers: LAL-CL02
Study First Received: December 17, 2012
Results First Received: January 14, 2016
Last Updated: February 13, 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
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Infant, Newborn, Diseases
Lipid Metabolism Disorders
Metabolic Diseases processed this record on May 25, 2017