Clinical trial NCT01488097: Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency
Official title: An Open Label Multicenter Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 in Adult Subjects With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency Who Previously Received Treatment in Study LAL-CL01
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cholesterol Ester Storage Disease (CESD)
Lysosomal Acid Lipase Deficiency
LAL-Deficiency
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 enzyme deficiency
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-08
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was an extension study to Study LAL-CL01 (NCT01307098). The primary objective of the study was to evaluate the long-term safety and tolerability of sebelipase alfa in participants with liver dysfunction due to lysosomal acid lipase (LAL) deficiency.

Detailed description: Participants who successfully received all 4 doses of sebelipase alfa in Study LAL-CL01 and opted to continue treatment in the extension study underwent screening assessments to determine study eligibility. Eligible participants initiated treatment in the extension study at least 4 weeks after their last dose of sebelipase alfa in Study LAL-CL01. This extension study consisted of a treatment period of up to 5 years, and a follow-up period of approximately 30 days after the last dose of sebelipase alfa.

Cholesteryl ester storage disease (CESD) is the late onset phenotype for LAL deficiency, a lysosomal storage disorder, which also has an early onset phenotype 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 patients with other liver conditions.

CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests (LFTs) and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some patients. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.

Eligibility criteria: Inclusion Criteria:

* Participant received all 4 scheduled doses of sebelipase alfa in Study LAL-CL01 with no life-threatening or unmanageable study drug toxicity.

Exclusion Criteria:

* Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances
* Clinically significant abnormal values on laboratory screening tests, other than LFTs or lipid panel tests

Primary outcomes:
measure: Number Of Participants Reporting TEAEs And IARs
timeFrame: From after first dose administration post-Baseline through EOS during study LAL-CL04
Secondary outcomes:
measure: Changes From Baseline In ALT And AST
timeFrame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
measure: Changes From Baseline In Liver Volume
timeFrame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
measure: Changes From Baseline In Liver Fat Content
timeFrame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260
measure: Changes From Baseline In GGT And ALP
timeFrame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
measure: Changes From Baseline In Serum Lipids
timeFrame: Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
measure: Changes From Baseline In Serum Ferritin
timeFrame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
measure: Changes From Baseline In Hs-CRP
timeFrame: Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS
Other outcomes:
Locations:
city: Eureka
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Minneapolis
country: United States
state: Minnesota
city: New York
country: United States
state: New York
city: Sudbury
country: Canada
state: Ontario
city: Prague
country: Czechia
city: Paris
country: France
city: Leeds
country: United Kingdom
city: Salford
country: United Kingdom
Study officials:
References:
citation: Balwani M, Breen C, Enns GM, Deegan PB, Honzik T, Jones S, Kane JP, Malinova V, Sharma R, Stock EO, Valayannopoulos V, Wraith JE, Burg J, Eckert S, Schneider E, Quinn AG. Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease. Hepatology. 2013 Sep;58(3):950-7. doi: 10.1002/hep.26289. Epub 2013 Mar 28.
citation: Malinova V, Balwani M, Sharma R, Arnoux JB, Kane J, Whitley CB, Marulkar S, Abel F. Sebelipase alfa for lysosomal acid lipase deficiency: 5-year treatment experience from a phase 2 open-label extension study. Liver Int. 2020 Sep;40(9):2203-2214. doi: 10.1111/liv.14603. Epub 2020 Aug 9.