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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Sebelipase alfa is a recombinant human lysosomal acid lipase enzyme. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL Deficiency. Dosing occurred qw for up to 5 years.
Unnamed facility
Irvine, California, United States
Unnamed facility
Cairo, Egypt
Unnamed facility
Grenoble, France
Unnamed facility
Paris, France
Unnamed facility
Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age
The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
Time frame: Month 12
Percentage Of Participants Surviving Beyond 12 Months Of Age
The percentage of participants in the PES who survived to at least 18 months of age.
Time frame: Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60
Median Age At Death
Participants in the PES who died during the study, including 3 participants who died after having received between 1 and 4 infusions of sebelipase alfa and 1 participant who died after approximately 40 weeks on treatment.
Time frame: Baseline to Week 260
Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles
Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Number Of Participants With Stunting, Wasting, Or Underweight
The number of participants who met criteria for the following dichotomous indicators of under nutrition were reported. These indicators included the following: * Stunting was defined as at least 2 standard deviations below the median for length-for-age/height-for-age; * Wasting was defined as wasting at least 2 standard deviations below the median for weight-for-length/weight-for-height; and * Underweight was defined as at least 2 standard deviations below the median for WFA.
Time frame: Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)
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Dublin, Ireland
Unnamed facility
London, United Kingdom
Unnamed facility
Manchester, United Kingdom
Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Ferritin
The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.
Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization [TFHN]
The number of participants achieving and maintaining TFHN are presented. For TFHN to be achieved, the participant must a) have had 2 post-baseline measurements of hemoglobin at least 4 weeks apart that were both above the age-adjusted lower limit of normal; b) have had no known additional measurements of hemoglobin that were below the age-adjusted lower limit of normal during the (minimum) 4-week period; and c) have had no transfusions during the (minimum) 4-week period, and also no transfusions for 2 weeks prior to the first hemoglobin measurement in the (minimum) 4-week period. For TFHN to be maintained, the participant must have been transfusion-free beginning at Week 6 and had all hemoglobin assessments above the lower limit of normal beginning in Week 8 and lasting at least 13 weeks.
Time frame: Baseline to Month 60