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
Interventional
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
Condition
Lysosomal Acid Lipase Deficiency
Intervention
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.
Publications
* 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
Drug
Estimated Enrollment
9
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.
Gender
All
Ages
N/A - 24 Months
Accepts Healthy Volunteers
No
Contacts
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Location Countries
Egypt
Location Countries
Egypt
Administrative Informations
NCT ID
NCT01371825
Organization ID
LAL-CL03
Responsible Party
Sponsor
Study Sponsor
Alexion Pharmaceuticals
Study Sponsor
, ,
Verification Date
January 2019