Clinical trial NCT01307098: Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency
Official title: An Open-Label Multicenter Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SBC-102 in Adult Participants With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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 Deficiency
Wolman disease
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-03-02
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Male or female participants ≥ 18 and ≤ 65 years of age
* Documented decreased LAL activity
* Evidence of liver involvement

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 liver function or lipid panel tests
* Aspartate aminotransferase and/or alanine aminotransferase persistently elevated \> 3x upper limit of normal at screening
* Previous hemopoietic bone marrow or liver transplant
* Current history of alcohol abuse

Primary outcomes:
measure: Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs)
timeFrame: Screening up to Day 52
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
state: California
city: New York
country: United States
state: New York
city: Pittsburgh
country: United States
state: Pennsylvania
city: Prague
country: Czechia
city: Paris
country: France
city: Cambridge
country: United Kingdom
city: Manchester
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.