Trial in Children With Growth Failure Due to Early Onset Lysosomal Acid Lipase (LAL) Deficiency/Wolman Disease

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Alexion Pharmaceuticals Identifier:
First received: June 9, 2011
Last updated: March 6, 2015
Last verified: March 2015
This is an open-label, repeat-dose, dose escalation study of SBC-102 (USAN: sebelipase alfa) in children with growth failure due to LAL Deficiency. Eligible subjects will receive once-weekly (qw) infusions of sebelipase alfa for up to 5 years

Condition Intervention Phase
Lysosomal Acid Lipase Deficiency
Wolman Disease
Drug: Sebelipase alfa (SBC-102)
Phase 2
Phase 3

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

Resource links provided by NLM:

Further study details as provided by Alexion Pharmaceuticals:

Primary Outcome Measures:
  • Survival at 12 months of age [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Long-term safety of sebelipase alfa in children with growth failure due to LAL Deficiency [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
  • Survival beyond 12 months of age. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: May 2011
Estimated Study Completion Date: December 2015
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Weekly IV infusions Dose A of sebelipase alfa
Drug: Sebelipase alfa (SBC-102)
Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL). The investigational medicinal product is an enzyme replacement therapy intended for treatment of patients with LAL Deficiency. Dosing will occur once weekly for up to three years.

Detailed Description:

Lysosomal Acid Lipase (LAL) Deficiency is a rare autosomal recessive lipid storage disorder that is caused by a marked decrease or almost complete absence of LAL, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids leads to hepatomegaly, liver dysfunction, and hepatic failure. Although a single disease, LAL Deficiency presents as a clinical continuum with two major phenotypes, Cholesteryl Ester Storage Disease (CESD) and Wolman Disease.

Early Onset LAL Deficiency (Wolman Disease) is extremely rare, with an estimated incidence of less than 2 lives per million. It is characterized by profound malabsorption, growth failure, and hepatic failure, and is usually fatal in the first year of life. There is currently no approved therapy for the treatment of LAL Deficiency.


Ages Eligible for Study:   up to 24 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject's parent or legal guardian provides written informed consent/permission prior to any study procedures.
  • Male or female child with documented decreased LAL activity relative to the normal range of the lab performing the assay or documented result of molecular genetic testing (2 mutations) confirming a diagnosis.
  • Growth failure with onset before 6 months of age.

Exclusion Criteria:

  • Clinically important concurrent disease.
  • Has received an investigational product other than sebelipase alfa within 14 days prior to the first dose.
  • Subject is older than 24 months of age.
  • Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplant.
  • Previous hematopoietic stem cell or liver transplant.
  • Known hypersensitivity to eggs.
  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: NCT01371825

United States, California
University of California, Irvine
Irvine, California, United States, 92697
United States, New York
North Shore Hospital Long Island Jewish Health System
Manhasset, New York, United States, 11030
Cairo, Egypt
Hopital Necker Enfants Malades
Paris, France
University of Mainz
Mainz, Germany
Mumbai, India
New Delhi, India
Dublin, Ireland
Azienda Ospedaliera Universita di Padova
Padova, Italy
Saudi Arabia
Riyadh, Saudi Arabia
National Taiwan University Hospital
Taipei, Taiwan
Ankara, Turkey
United Kingdom
St. Mary's Hospital, Central Manchester University Hospitals
Manchester, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
  More Information

Responsible Party: Alexion Pharmaceuticals Identifier: NCT01371825     History of Changes
Other Study ID Numbers: LAL-CL03 
Study First Received: June 9, 2011
Last Updated: March 6, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence nationale de sécurité du médicament
Germany: Bundesinstitut fur Arzneimittel und Medizinprodukte
Italy: Italian Medicines Agency (AIFA)
Taiwan: Department of Health
Ireland: Health Products Regulatory Authority (HPRA)

Keywords provided by Alexion Pharmaceuticals:
Wolman Disease
Wolman Phenotype
Acid Lipase Deficiency
Acid Cholesteryl Hydrolase
Acid Lipase Disease Deficiency, type 2
Cholesteryl Ester Storage Disease (CESD)
Cholesteryl Ester Hydrolase Deficiency
Early Onset Lysosomal Acid Lipase Deficiency (Wolman Disease)
LAL Deficiency
Late Onset Lysosomal Acid Lipase Deficiency (CESD)
Wolman Disease (early onset LAL Deficiency)
Related Disorders:
Non-alcoholic Fatty Liver Disease (NAFLD)
Non-alcoholic Steatohepatitis (NASH)
Alcoholic Liver Disease
Cryptogenic Cirrhosis
Niemann-Pick Disease (NPD) Type C
Chanarin Dorfman Syndrome

Additional relevant MeSH terms:
Failure to Thrive
Wolman Disease
Cholesterol Ester Storage Disease
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Signs and Symptoms processed this record on February 11, 2016