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: April 5, 2016
Last verified: April 2016
This is an open-label, repeat-dose, intra-subject 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: 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:
  • Percentage of Subjects in the PES Surviving to 12 Months of Age [ Time Frame: From week 0 to data cut-off (27 to 164 weeks of treatment) ] [ Designated as safety issue: No ]
    The primary efficacy endpoint was the percentage of subjects (%) in the Primary Efficacy Analysis Set (PES) who survived to at least 12 months of age.

Secondary Outcome Measures:
  • Percentage of Subjects in the PES Surviving at 18 Months of Age [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ] [ Designated as safety issue: No ]
    The percentage of subjects in the Primary Efficacy Analysis Set (PES) who survived to at least 18 months of age.

  • Percentage of Subjects in the PES Surviving at 24 Months of Age [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ] [ Designated as safety issue: No ]
    The percentage of subjects in the Primary Efficacy Analysis Set (PES) who survived to at least 24 months of age.

  • Median Age at Death [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ] [ Designated as safety issue: No ]
  • Effect on Growth Parameters (Weight-for-age) [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ] [ Designated as safety issue: No ]
    Changes from baseline in percentiles for weight-for-age (WFA)

  • Dichotomous Growth Status Indicators [ Time Frame: Month 12 of treatment ] [ Designated as safety issue: No ]
    The percentages of subjects meeting criteria for each dichotomous indicator of under nutrition, i.e., underweight (at least 2 SD below median for weight-for-age [WFA]), wasting (at least 2 SD below median for weight-for-length or -height [WFL/WFH]), and stunting (at least 2 SD below median for length- or height-for-age [LFA/HFA])

  • Changes in Serum Transaminases [ Time Frame: from week 0 to weeks 1 and 4 ] [ Designated as safety issue: No ]
    Change from baseline for alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

  • Change in Serum Ferritin [ Time Frame: from week 0 to week 1 ] [ Designated as safety issue: No ]
    Change from baseline in serum ferritin

  • Percentage of Subjects Achieving Transfusion-free Hemoglobin Normalization [ Time Frame: from week 0 to data cut-off (27 to 164 weeks of treatment) ] [ Designated as safety issue: No ]
    The percentage of subjects achieving transfusion-free hemoglobin normalization (TFHN) of ≥ 4 weeks at any time during the study (also referred to as short-term TFHN), and the percentage of subjects who maintained TFHN for ≥ 13 weeks beginning at Week 6 (also referred to as sustained early TFHN). A subject was considered to have achieved short-term TFHN if the/she had two post-baseline measurements of hemoglobin, obtained at least 4 weeks apart, that were above the age-adjusted lower limit of normal (LLN), and had no additional hemoglobin measurements below LLN during this minimum 4-week period and no transfusions administered during the minimum 4-week period or for 2 weeks prior to the start of this period.

Enrollment: 9
Study Start Date: May 2011
Estimated Study Completion Date: April 2018
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-Label sebelipase alfa
All subjects received IV infusions of sebelipase alfa during the open-label treatment period. Subjects received a starting dose of 0.35 mg/kg once weekly (qw) and, after demonstrating acceptable safety and tolerability after at least 2 infusions at this dose, began receiving the per-protocol dose of 1 mg/kg qw. Thereafter, subjects were to continue receiving a dose of 1 mg/kg qw for the duration of the treatment period. However, in the event of disease progression (based on protocol-defined criteria) at any time during treatment with 1 mg/kg qw, an individual subject could receive a dose increase to 3 mg/kg qw and; if necessary, a subsequent dose increase to 5 mg/kg qw (after review and approval by a Safety Committee). Subjects receiving long-term treatment on a stable qw dose could be switched to an every other week (qow) dosing schedule at the same total dose (mg/kg) per infusion.
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
Results First Received: January 14, 2016
Last Updated: April 5, 2016
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:
Niemann-Pick Disease (NPD) Type C
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
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 May 26, 2016