Safety and Efficacy Study of Sebelipase Alfa in Participants With Lysosomal Acid Lipase Deficiency

NCT02112994 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LAL-CL062011-004287-30
• Study Type: interventional
• Target: 31
• Locations: 15 countries
• Sites: 19

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).

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

Outcome Measures

Primary Outcomes (1)

• Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)

  The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received.

  Screening, Week 144

Secondary Outcomes (4)

• Percent Change In Serum Lipids From Baseline To Week 144

  Baseline, Week 144

• Participants Testing Positive For Anti-drug Antibodies (ADAs)

  Week 144

• Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants

  Baseline, Week 144

• Shift In Child-Pugh Status From Baseline To Week 144

  Baseline, Week 144

Study Arms (1)

Sebelipase Alfa

EXPERIMENTAL

Pediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status.

Drug: Sebelipase Alfa

Interventions

Sebelipase Alfa DRUG

IV infusion of sebelipase alfa

Also known as: SBC-102

Sebelipase Alfa

Eligibility Criteria

• Age: 8 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant was \>8 months of age at the time of dosing.
• 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.
• 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
• 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

You may not qualify if:

• Participant had known causes of active liver disease other than LAL-D, which had not been adequately treated.
• Participant received a hematopoietic stem cell or liver transplant \<2 years from the time of dosing.
• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (19)

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Shreveport, Louisiana, 71103, United States

Location

Unknown Facility

Cincinnati, Ohio, 45229, United States

Location

Unknown Facility

Westmead, NSW 2145, Australia

Location

Unknown Facility

Brussels, 1200, Belgium

Location

Unknown Facility

São Paulo, 04024-002, Brazil

Location

Unknown Facility

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Unknown Facility

Zagreb, 10000, Croatia

Location

Unknown Facility

Copenhagen, 2100, Denmark

Location

Unknown Facility

Freiburg im Breisgau, 79106, Germany

Location

Unknown Facility

Padua, 35128, Italy

Location

Unknown Facility

Mexico City, 06720, Mexico

Location

Unknown Facility

Amsterdam, 1105, Netherlands

Location

Unknown Facility

Moscow, 117997, Russia

Location

Unknown Facility

A Coruña, 15006, Spain

Location

Unknown Facility

Barcelona, 08036, Spain

Location

Unknown Facility

Madrid, 28046, Spain

Location

Unknown Facility

Balcalı, 01300, Turkey (Türkiye)

Location

Unknown Facility

Birmingham, B4 6NH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35442238 DERIVED

MeSH Terms

Conditions

Wolman Disease; Lysosomal Storage Diseases; Cholesterol Ester Storage Disease; Metabolic Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lipid Metabolism Disorders; Infant, Newborn, Diseases

Interventions

Sebelipase alfa

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: April 14, 2014
• Study Start: June 24, 2014
• Primary Completion: December 28, 2017
• Study Completion: December 28, 2017
• Last Updated: December 4, 2019
• Results First Posted: January 15, 2019

Record last verified: 2019-11

Locations

CR (1); ME (1); CA (1); US (3); DE (1); ES (3); IT (1); BR (1); DK (1); GB (1); RU (1); AU (1); BE (1); NL (1); TU (1)