Clinical Study In Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

NCT02193867 | Terminated Phase 2 Results DMC

• 1 other identifier: LAL-CL08
• Study Type: interventional
• Target: 10
• Locations: 4 countries
• Sites: 5

Brief Summary

This was an open-label, repeat-dose, study of sebelipase alfa in infants with rapidly progressive lysosomal acid lipase deficiency (LAL-D). Eligible participants received once-weekly infusions of sebelipase alfa for up to 3 years.

Conditions

Lysosomal Acid Lipase Deficiency

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)

• 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 were obtained through spontaneous reporting or elicited by specific questioning or examination of the participant's parent or legal guardian. An adverse event was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant, whether or not causally related to administration of study drug. Adverse event severity was graded by the Investigator as mild, moderate, or severe based on definitions developed from Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Adverse events reporting was from the date of informed consent until completion of the follow-up visit at approximately 30 days after the last dose of study drug. A summary of all serious and other nonserious AEs regardless of causality is located in the Reported AE module.

  Screening through Month 37

Secondary Outcomes (7)

• Percentage Of Participants Surviving To 12, 18, 24, And 36 Months Of Age

  Baseline through Month 12, Month 18, Month 24, and Month 36

• Median Age At Death

  Baseline through Month 36

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

  Baseline, Month 12, Month 24, and Month 36

• Number Of Participants With Stunting, Wasting, Or Underweight At Baseline, 12, 24, And 36 Months

  Baseline to Month 12, Month 24, and Month 36

• Change From Baseline In Serum Transaminases (ALT And AST) At Month 12, 24, And 36

  Baseline, Month 12, Month 24, and Month 36

Study Arms (1)

Open-Label Sebelipase Alfa

EXPERIMENTAL

All participants initiated once weekly (qw) intravenous (IV) infusions with sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) qw. A participant who met protocol defined dose escalation criteria at a dose of 1 mg/kg qw could be considered for a dose escalation to 3 mg/kg qw. If a participant continued to meet dose escalation criteria after at least 4 infusions at a dose of 3 mg/kg qw, the participant could be considered for a further dose escalation to 5 mg/kg qw. Under country-specific provisions (United Kingdom only), participants could be considered for a further dose escalation to 7.5 mg/kg qw if a thorough case review indicated that a participant continued to have evidence of disease progression at a dose of 5 mg/kg qw. All dose escalations were contingent upon acceptable safety and tolerability of preceding infusions and were undertaken by mutual agreement of the Investigator and Sponsor and after approval by an independent safety committee.

Drug: Sebelipase Alfa

Interventions

Sebelipase Alfa DRUG

Sebelipase alfa is a recombinant human lysosomal acid lipase. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL-D. Dosing occurred once weekly for up to 3 years.

Also known as: SBC-102

Open-Label Sebelipase Alfa

Eligibility Criteria

• Age: Up to 8 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant's parent or legal guardian (if applicable) consent to participation in the study
• Confirmation of documented decreased LAL activity relative to the normal range of the lab performing the assay or confirmation of LAL-D diagnosis as determined by a Sponsor-approved central laboratory
• Substantial clinical concerns, in the opinion of Investigator and Sponsor, of rapid disease progression requiring urgent medical intervention including, but not restricted to the following:
• Marked abdominal distension and hepatomegaly
• Failure to thrive
• Disturbance of coagulation
• Severe anemia
• Sibling with rapidly progressive course of LAL-D

You may not qualify if:

• Clinically important concurrent disease
• Participant was \> 8 months of age at the time of first dosing
• Participant received an investigational medicinal product other than sebelipase alfa within 14 days prior to the first dose of sebelipase alfa in this study
• Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplantation
• Previous hematopoietic stem cell or liver transplant
• Known hypersensitivity to eggs

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (5)

Unknown Facility

Phoenix, Arizona, 85016, United States

Location

Unknown Facility

Kuopio, Finland

Location

Unknown Facility

Naples, Italy

Location

Unknown Facility

Birmingham, United Kingdom

Location

Unknown Facility

Manchester, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 23348766 BACKGROUND

• Jones SA, Valayannopoulos V, Schneider E, Eckert S, Banikazemi M, Bialer M, Cederbaum S, Chan A, Dhawan A, Di Rocco M, Domm J, Enns GM, Finegold D, Gargus JJ, Guardamagna O, Hendriksz C, Mahmoud IG, Raiman J, Selim LA, Whitley CB, Zaki O, Quinn AG. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet Med. 2016 May;18(5):452-8. doi: 10.1038/gim.2015.108. Epub 2015 Aug 27.

  PMID: 26312827 BACKGROUND

• 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: July 7, 2014
• First Posted: July 18, 2014
• Study Start: June 6, 2014
• Primary Completion: October 30, 2018
• Study Completion: October 30, 2018
• Last Updated: November 18, 2019
• Results First Posted: November 18, 2019

Record last verified: 2019-10

Locations

FI (1); GB (2); US (1); IT (1)