Phase 3
N=66
Acid Lipase Replacement Investigating Safety and Efficacy (ARISE) in Participants With Lysosomal Acid Lipase Deficiency
Lysosomal Acid Lipase Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT01757184 ↗Enrolled (actual)
66
Serious AEs
10.6%
Results posted
Apr 2016
Primary outcome: Primary: Percentage Of Participants Achieving Alanine Aminotransferase Normalization — 31; 7; 56; 37 percentage of participants — p=0.0271
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sebelipase Alfa (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 4+ yrs
- Sex
- All
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Primary completion
- May 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage Of Participants Achieving Alanine Aminotransferase Normalization |
31; 7; 56; 37 | 0.0271 sig |
| SECONDARY Percent Change From Baseline In Low-density Lipoprotein Cholesterol (LDL-C) |
-28.42; -6.25; -19.74; -18.09 | <0.0001 sig |
| SECONDARY Percent Change From Baseline In Non-high Density Lipoprotein Cholesterol (Non-HDL-C) |
-27.97; -6.94; -19.75; -18.34 | <0.0001 sig |
| SECONDARY Percentage Of Participants Achieving Aspartate Aminotransferase Normalization |
42; 3; 69; 62 | 0.0003 sig |
| SECONDARY Percent Change From Baseline In Triglycerides |
-25.45; -11.14; -11.87; -19.63 | 0.0375 sig |
| SECONDARY Percent Change From Baseline In High-density Lipoprotein Cholesterol (HDL-C) |
19.57; -0.29; 31.65; 34.78 | <0.0001 sig |
| SECONDARY Percent Change From Baseline In Liver Fat Content |
-31.98; -4.21; -9.89; -0.93 | <0.0001 sig |
| SECONDARY Participants With Improvement In Liver Histopathology (Decrease Of > 5% In Hepatic Steatosis Score) |
10; 4; 7; 4 | 0.4216 |
| SECONDARY Percent Change From Baseline In Liver Volume |
-10.28; -2.66; -24.04; -21.55 | 0.0068 sig |
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.
Data sourced from ClinicalTrials.gov (NCT01757184). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.