Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Patients With Lysosomal Acid Lipase Deficiency

This study has been completed.
Information provided by (Responsible Party):
Alexion Pharmaceuticals Identifier:
First received: March 1, 2011
Last updated: June 2, 2014
Last verified: June 2014
This is the first clinical study of SBC-102 (sebelipase alfa) for the treatment of LAL Deficiency. It is an open label dose escalation study in adult patients with liver dysfunction due to Lysosomal Acid Lipase (LAL) Deficiency and will examine three doses of SBC-102 (sebelipase alfa). The targeted number for this study is 9 evaluable subjects.

Condition Intervention Phase
Cholesterol Ester Storage Disease(CESD)
Lysosomal Acid Lipase Deficiency
Drug: SBC-102 (sebelipase alfa)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Multicenter Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Patients With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency

Resource links provided by NLM:

Further study details as provided by Alexion Pharmaceuticals:

Primary Outcome Measures:
  • Safety and Tolerability of SBC-102 (sebelipase alfa) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    The safety and tolerability of weekly infusions of SBC-102 (sebelipase alfa) will be assessed by routine monitoring of patients for adverse events (AEs) and monitoring changes from baseline in physical examination findings, vital signs, clinical laboratory evaluations, immunogenicity tests and concomitant therapies.

Secondary Outcome Measures:
  • Pharmacokinetics of SBC-102 (sebelipase alfa) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Characterize the pharmacokinetics of SBC-102 (sebelipase alfa) delivered by IV infusion after single and multiple doses.

Enrollment: 9
Study Start Date: May 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Cohort 1: Weekly IV infusions of Dose A of SBC-102 (sebelipase alfa)
Drug: SBC-102 (sebelipase alfa)
Weekly IV infusions Dose A of SBC-102 (sebelipase alfa)
Experimental: Cohort 2
Cohort 2: Weekly IV infusions of Dose B of SBC-102 (sebelipase alfa)
Drug: SBC-102 (sebelipase alfa)
Weekly IV infusions Dose B of SBC-102 (sebelipase alfa)
Experimental: Cohort 3
Cohort 3: Weekly IV infusions of Dose C of SBC-102 (sebelipase alfa)
Drug: SBC-102 (sebelipase alfa)
Weekly IV infusions Dose C of SBC-102 (sebelipase alfa)

Detailed Description:

Cholesteryl Ester Storage Disease (CESD) is the late onset phenotype for Lysosomal Acid Lipase (LAL) Deficiency, a Lysosomal Storage Disorder, which also has an early onset phenotype known as Wolman Disease 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.

Disease Risk In Families:

  • 25 per million incidence
  • Autosomal recessive disorder, LAL deficiency is carried on chromosome 10
  • Parents with an affected son or daughter have a 1 in 4 chance of having another affected child

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male or female patients ≥ 18 and ≤ 65 years of age
  • Documented decreased LAL activity
  • Evidence of liver involvement

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 liver function or lipid panel tests
  • AST and/or ALT persistently elevated > 3xULN at screening
  • Previous hemopoietic bone marrow or liver transplant
  • Current history of alcohol abuse
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01307098

United States, California
Palo Alto, California, United States
United States, New York
New York, New York, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
Czech Republic
Prague, Czech Republic
Paris, France
United Kingdom
Cambridge, United Kingdom
Manchester, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
  More Information

Additional Information:
Responsible Party: Alexion Pharmaceuticals Identifier: NCT01307098     History of Changes
Other Study ID Numbers: LAL-CL01 
Study First Received: March 1, 2011
Last Updated: June 2, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Czech Republic: State Institute for Drug Control

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:
Cholesterol Ester Storage Disease
Wolman Disease
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors processed this record on May 25, 2016