Clinical trial NCT01371825: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Lysosomal Acid Lipase Deficiency
Wolman Disease
Keywords: LIPA
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
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-06-13
Enrollment: 9
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age
timeFrame: Month 12
Secondary outcomes:
measure: Percentage Of Participants Surviving Beyond 12 Months Of Age
timeFrame: Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60
measure: Median Age At Death
timeFrame: Baseline to Week 260
measure: Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
measure: Number Of Participants With Stunting, Wasting, Or Underweight
timeFrame: Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
measure: Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN]
timeFrame: Baseline to Month 60
Other outcomes:
Locations:
city: Irvine
country: United States
state: California
city: Cairo
country: Egypt
city: Grenoble
country: France
city: Paris
country: France
city: Dublin
country: Ireland
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
References:
citation: Jones SA, Rojas-Caro S, Quinn AG, Friedman M, Marulkar S, Ezgu F, Zaki O, Gargus JJ, Hughes J, Plantaz D, Vara R, Eckert S, Arnoux JB, Brassier A, Le Quan Sang KH, Valayannopoulos V. Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study. Orphanet J Rare Dis. 2017 Feb 8;12(1):25. doi: 10.1186/s13023-017-0587-3.