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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01307098
Recruitment Status : Completed
First Posted : March 2, 2011
Last Update Posted : July 27, 2016
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
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 or disease Intervention/treatment Phase
Cholesterol Ester Storage Disease(CESD) Lysosomal Acid Lipase Deficiency Drug: SBC-102 (sebelipase alfa) Phase 1

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2011
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Arm Intervention/treatment
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)
Other Name: Kanuma

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)
Other Name: Kanuma

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)
Other Name: Kanuma

Primary Outcome Measures :
  1. Safety and Tolerability of SBC-102 (sebelipase alfa) [ Time Frame: 4 weeks ]
    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 :
  1. Pharmacokinetics of SBC-102 (sebelipase alfa) [ Time Frame: 4 weeks ]
    Characterize the pharmacokinetics of SBC-102 (sebelipase alfa) delivered by IV infusion after single and multiple doses.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01307098

United States, California
Stanford University
Palo Alto, California, United States, 94305
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Pennsylvania
University of Pittsburg
Pittsburgh, Pennsylvania, United States, 15524
Czech Republic
General University Hospital in Prague
Prague, Czech Republic, 12808
Hopital Necker Enfants Malades
Paris, France, 75015
United Kingdom
Addenbrooke's Hospital, NHS Trust
Cambridge, United Kingdom, CB20QQ
Royal Manchester Children's Hospital
Manchester, United Kingdom, M139WL
Sponsors and Collaborators
Alexion Pharmaceuticals

Additional Information:
Publications of Results:
Responsible Party: Alexion Pharmaceuticals Identifier: NCT01307098     History of Changes
Other Study ID Numbers: LAL-CL01
First Posted: March 2, 2011    Key Record Dates
Last Update Posted: July 27, 2016
Last Verified: June 2014
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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