Children With Lysosomal Acid Lipase Deficiency Who Previously Received Treatment With SBC-102

Brief Title

Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency

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

Brief Summary

      This was an open-label, repeat-dose, intra-participant dose-escalation study of SBC-102
      (sebelipase alfa) in children with growth failure due to lysosomal acid lipase (LAL)
      Deficiency. Eligible participants received once-weekly (qw) infusions of sebelipase alfa for
      up to 5 years.

Detailed Description

      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 2 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.

Study Phase

Phase 2/Phase 3

Study Type


Primary Outcome

Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age

Secondary Outcome

 Percentage Of Participants Surviving Beyond 12 Months Of Age


Lysosomal Acid Lipase Deficiency


Sebelipase alfa (SBC-102)

Study Arms / Comparison Groups

 Open-Label Sebelipase Alfa
Description:  Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant's dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

May 4, 2011

Completion Date

January 3, 2018

Primary Completion Date

January 3, 2018

Eligibility Criteria

        Inclusion Criteria:

          -  Participant's parent or legal guardian provided 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 laboratory 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 or comorbidities.

          -  Had received an investigational product other than sebelipase alfa within 14 days
             prior to the first dose.

          -  Participant was 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.




N/A - 24 Months

Accepts Healthy Volunteers



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Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Alexion Pharmaceuticals

Study Sponsor

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Verification Date

January 2019