Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency

NCT01371825 | Completed Phase 2 Results DMC

• 1 other identifier: LAL-CL03
• Study Type: interventional
• Target: 9
• Locations: 5 countries
• Sites: 7

Brief Summary

This was an open-label, repeat-dose, intra-participant dose-escalation study of SBC-102 (sebelipase alfa) in children with growth failure due to lysosomal acid lipase (LAL) Deficiency. Eligible participants received once-weekly (qw) infusions of sebelipase alfa for up to 5 years.

Conditions

Lysosomal Acid Lipase Deficiency; Wolman Disease

Keywords

LIPA; Wolman Disease; Wolman Phenotype; Acid Lipase Deficiency; Acid Cholesteryl Hydrolase; Acid Lipase Disease Deficiency, type 2; Cholesteryl Ester Storage Disease (CESD); Cholesteryl Ester Hydrolase Deficiency; Early Onset Lysosomal Acid Lipase Deficiency (Wolman Disease); LAL Deficiency; Late Onset Lysosomal Acid Lipase Deficiency (CESD); Wolman Disease (early onset LAL Deficiency); Related Disorders:; Non-alcoholic Fatty Liver Disease (NAFLD); Non-alcoholic Steatohepatitis (NASH); Alcoholic Liver Disease; Cryptogenic Cirrhosis; Niemann-Pick Disease (NPD) Type C; Chanarin Dorfman Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage Of Participants In The Primary Efficacy Analysis Set (PES) Surviving To 12 Months Of Age

  The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.

  Month 12

Secondary Outcomes (7)

• Percentage Of Participants Surviving Beyond 12 Months Of Age

  Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60

• Median Age At Death

  Baseline to Week 260

• Change From Baseline To Months 12, 24, 36, 48, And 60 In Weight For Age (WFA) Percentiles

  Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

• Number Of Participants With Stunting, Wasting, Or Underweight

  Baseline to Month 12, Month 24, Month 36, Month 48, and Month 60

• Change From Baseline To Months 12, 24, 36, 48, And 60 In Serum Transaminases (ALT And AST)

  Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

Study Arms (1)

Open-Label Sebelipase Alfa

EXPERIMENTAL

Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant's dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.

Drug: Sebelipase alfa (SBC-102)

Interventions

Sebelipase alfa (SBC-102) DRUG

Sebelipase alfa is a recombinant human lysosomal acid lipase enzyme. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL Deficiency. Dosing occurred qw for up to 5 years.

Open-Label Sebelipase Alfa

Eligibility Criteria

• Age: Up to 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant's parent or legal guardian provided written informed consent/permission prior to any study procedures.
• Male or female child with documented decreased LAL activity relative to the normal range of the laboratory performing the assay or documented result of molecular genetic testing (2 mutations) confirming a diagnosis.
• Growth failure with onset before 6 months of age.

You may not qualify if:

• Clinically important concurrent disease or comorbidities.
• Had received an investigational product other than sebelipase alfa within 14 days prior to the first dose.
• Participant was older than 24 months of age.
• Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplant.
• Previous hematopoietic stem cell or liver transplant.
• Known hypersensitivity to eggs.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (7)

Unknown Facility

Irvine, California, 92697, United States

Location

Unknown Facility

Cairo, 11771, Egypt

Location

Unknown Facility

Grenoble, 38700, France

Location

Unknown Facility

Paris, 75015, France

Location

Unknown Facility

Dublin, 1, Ireland

Location

Unknown Facility

London, SE1 7EH, United Kingdom

Location

Unknown Facility

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Jones SA, Rojas-Caro S, Quinn AG, Friedman M, Marulkar S, Ezgu F, Zaki O, Gargus JJ, Hughes J, Plantaz D, Vara R, Eckert S, Arnoux JB, Brassier A, Le Quan Sang KH, Valayannopoulos V. Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study. Orphanet J Rare Dis. 2017 Feb 8;12(1):25. doi: 10.1186/s13023-017-0587-3.

  PMID: 28179030 BACKGROUND

MeSH Terms

Conditions

Wolman Disease; Cholesterol Ester Storage Disease; Non-alcoholic Fatty Liver Disease; Liver Diseases, Alcoholic; Cirrhosis, Cryptogenic; Niemann-Pick Diseases; Chanarin-Dorfman Syndrome

Interventions

Sebelipase alfa

Condition Hierarchy (Ancestors)

Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Infant, Newborn, Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic 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
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2011
• First Posted: June 13, 2011
• Study Start: May 4, 2011
• Primary Completion: January 3, 2018
• Study Completion: January 3, 2018
• Last Updated: January 30, 2019
• Results First Posted: April 18, 2016

Record last verified: 2019-01

Locations

US (1); EG (1); IE (1); GB (2); FR (2)