Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency
Condition: Cholesterol Ester Storage Disease(CESD); Lysosomal Acid Lipase Deficiency; LAL-Deficiency
MeSH terms: Wolman Disease; Cholesterol Ester Storage Disease
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This was the first clinical study of SBC-102 (sebelipase alfa) for the treatment of Lysosomal
      Acid Lipase (LAL) Deficiency. It was an open-label dose escalation study in adult
      participants with liver dysfunction due to LAL Deficiency and was designed to examine 3 doses
      of sebelipase alfa. The targeted number for this study was 9 evaluable participants.
    

Detailed description: 
      The study was composed of a screening period, a treatment period, and a post-treatment
      follow-up period (including an End of Study visit). Participants who successfully completed
      screening assessments to determine study eligibility were allocated to 3 sequential cohorts
      (0.35, 1, or 3 milligrams/kilogram [mg/kg]). Within each cohort, one participant was
      initially dosed and, if sebelipase alfa was deemed safe and well tolerated in this
      participant (based on at least 24 hours of monitoring), dosing was allowed to be initiated
      for the remaining participants in the cohort. Initiation of dosing in the next cohort
      occurred only after all participants in the preceding cohort had been monitored for at least
      5 days after the second infusion, without any evidence of significant safety signals, and an
      independent Safety Committee had reviewed the cumulative safety data and provided their
      recommendation on the acceptability of beginning dosing in the next cohort.

      Cholesteryl Ester Storage Disease (CESD) is the late onset phenotype for LAL Deficiency, a
      lysosomal storage disorder, which also has an early onset phenotype known as Wolman disease
      that primarily affects infants. CESD can present in childhood but often goes unrecognized
      until adulthood when the underlying pathology is advanced. Many of the signs and symptoms are
      common to participants with other liver conditions.

      CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly,
      persistently abnormal liver function tests and type II hyperlipidemia. Splenomegaly and
      evidence of mild hypersplenism may affect some participants. Untreated, CESD may lead to
      fibrosis, cirrhosis, liver failure and death.
    

Intervention name(s): Sebelipase alfa 0.35 mg/kg; Sebelipase alfa 1 mg/kg; Sebelipase alfa 3 mg/kg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Sebelipase alfa is a recombinant human lysosomal acid lipase.; Sebelipase alfa is a recombinant human lysosomal acid lipase.; Sebelipase alfa is a recombinant human lysosomal acid lipase.
Other intervention name(s): Kanuma; SBC-102; Kanuma; SBC-102; Kanuma; SBC-102
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Enzyme Replacement Therapy (ERT); Lysosomal Storage Disease; Late Onset Lysosomal Acid Lipase (LAL) Deficiency; Acid cholesteryl ester hydrolase deficiency, type 2; Acid lipase disease; Cholesterol ester hydrolase deficiency; LAL Deficiency; LIPA Deficiency; Wolman disease