Acid Lipase Replacement Investigating Safety and Efficacy (ARISE) in Participants With Lysosomal Acid Lipase Deficiency
Condition: Lysosomal Acid Lipase Deficiency
MeSH terms: Wolman Disease
Intervention: Sebelipase Alfa; Placebo
Intervention description: IV infusions of sebelipase alfa; IV infusions of matched placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 66.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: Enzyme replacement therapy (ERT); Lysosomal storage disease; Late-onset lysosomal acid lipase deficiency (LAL-D); Acid cholesteryl ester hydrolase deficiency, type 2; Acid lipase disease; Cholesterol ester hydrolase deficiency; LAL-D; LIPA deficiency; Wolman disease; Cholesterol ester storage disease (CESD)

Summary:

      This Phase 3 study evaluated the efficacy and safety of 1 milligram/kilogram (mg/kg)
      intravenous (IV) infusions of SBC-102 (sebelipase alfa) administered every other week (qow)
      in participants with late onset lysosomal acid lipase deficiency (LAL-D) (cholesteryl ester
      storage disease [CESD]).

      Late-onset LAL-D is an underappreciated cause of cirrhosis, liver failure and dyslipidemia.
      There is currently no standard treatment for LAL-D other than supportive care. Enzyme
      replacement therapy may be a potential new treatment option for LAL-D participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant and/or participant's parent or legal guardian provided informed consent.

          -  Participant was ≥ 4 years of age on the date of informed consent.

          -  Deficiency of LAL enzyme activity confirmed by dried blood spot testing at screening.

          -  Alanine aminotransferase ≥ 1.5x upper limit of normal on 2 consecutive screening
             measurements obtained at least 1 week apart.

          -  Female participants of childbearing potential must not have been pregnant or
             breastfeeding and must have agreed to use a medically acceptable method of preventing
             contraception from screening until 4 weeks after the last dose of study drug.

          -  Participant receiving lipid-lowering therapies must have been on a stable dose of the
             medication for at least 6 weeks prior to randomization and was willing to remain on a
             stable dose for at least the first 32 weeks of treatment in the study.

          -  Participant receiving medications for the treatment of nonalcoholic fatty liver
             disease must have been on a stable dose for at least 16 weeks prior to randomization
             and was willing to remain on a stable dose for at least the first 32 weeks of
             treatment in the study.

        Exclusion Criteria:

          -  Severe hepatic dysfunction (Child-Pugh Class C).

          -  Other medical conditions or comorbidities, which, in the opinion of the Investigator,
             would have interfered with study compliance or data interpretation.

          -  Previous hematopoietic or liver transplant procedure.

          -  Received treatment with high-dose corticosteroids (acute or chronic) within 26 weeks.
             (Note: Participants receiving maintenance therapy with low-dose oral, intranasal,
             topical, or inhaled corticosteroids were considered eligible for the study).

          -  Known hypersensitivity to eggs.

          -  Participated in a study employing an investigational medicinal product within 4 weeks
             prior to randomization.