Clinical trial NCT02112994: Safety and Efficacy Study of Sebelipase Alfa in Participants With Lysosomal Acid Lipase Deficiency
Official title: A Multi-Center, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lysosomal Acid Lipase 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
Additional relevant MeSH terms:
Cholesterol Ester Storage Disease
Metabolic Diseases
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Lipid Metabolism Disorders
Infant, Newborn, Diseases
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-04-14
Enrollment: 31
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D).

Detailed description: The primary objective of this study was to evaluate the safety of intravenous (IV) infusions of sebelipase alfa in a more broad population of LAL-D participants than previously studied. Such participants may have been excluded from enrollment in other studies of LAL-D because of age, disease progression, previous treatment by hematopoietic stem cell or liver transplantation, less common disease manifestations, or disease characteristics that would preclude participation in a placebo-controlled study. This open-label study included infants \>8 months, children, and adults. At least 4 participants in the study were to be between the age of 2 and 4 years. Eligible participants received sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) every other week (qow).

Eligibility criteria: Key Inclusion Criteria:

1. Participant was \>8 months of age at the time of dosing.
2. Confirmation of LAL-D diagnosis as determined by the central laboratory or, for participants with prior hematopoietic stem cell transplant or liver transplant, historical enzyme activity or molecular genetic testing confirming a diagnosis of LAL-D.
3. Participants \>8 months but \<4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:

   * Dyslipidemia
   * Elevated transaminases
   * Impaired growth
   * Suspected malabsorption
   * Other clinical manifestation of LAL-D
4. Participants ≥4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:

   * Evidence of advanced liver disease
   * Histologically confirmed disease recurrence in participants with past liver or hematopoietic transplant
   * Persistent dyslipidemia
   * Suspected malabsorption
   * Other clinical manifestation of LAL-D

Key Exclusion Criteria:

1. Participant had known causes of active liver disease other than LAL-D, which had not been adequately treated.
2. Participant received a hematopoietic stem cell or liver transplant \<2 years from the time of dosing.
3. Participant with co-morbidities other than complications due to LAL-D, which were irreversible or associated with a high mortality risk within 6 months or would interfere with study compliance or data interpretation.

Primary outcomes:
measure: Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
timeFrame: Screening, Week 144
Secondary outcomes:
measure: Percent Change In Serum Lipids From Baseline To Week 144
timeFrame: Baseline, Week 144
measure: Participants Testing Positive For Anti-drug Antibodies (ADAs)
timeFrame: Week 144
measure: Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants
timeFrame: Baseline, Week 144
measure: Shift In Child-Pugh Status From Baseline To Week 144
timeFrame: Baseline, Week 144
Other outcomes:
Locations:
city: Chicago
country: United States
state: Illinois
city: Shreveport
country: United States
state: Louisiana
city: Cincinnati
country: United States
state: Ohio
city: Westmead
country: Australia
city: Brussels
country: Belgium
city: Sao Paulo
country: Brazil
city: Halifax
country: Canada
state: Nova Scotia
city: Zagreb
country: Croatia
city: Copenhagen
country: Denmark
city: Freiburg
country: Germany
city: Padova
country: Italy
city: Mexico City
country: Mexico
city: Amsterdam
country: Netherlands
city: Moscow
country: Russian Federation
city: A Coruna
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Balcali
country: Turkey
city: Birmingham
country: United Kingdom
Study officials:
References:
citation: Burton BK, Sanchez AC, Kostyleva M, Martins AM, Marulkar S, Abel F, Baric I. Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2022 Jun 1;74(6):757-764. doi: 10.1097/MPG.0000000000003452. Epub 2022 Apr 19.