Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency

NCT01488097 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LAL-CL04
• Study Type: interventional
• Target: 8
• Locations: 5 countries
• Sites: 10

Brief Summary

This was an extension study to Study LAL-CL01 (NCT01307098). The primary objective of the study was to evaluate the long-term safety and tolerability of sebelipase alfa in participants with liver dysfunction due to lysosomal acid lipase (LAL) deficiency.

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 enzyme deficiency

Outcome Measures

Primary Outcomes (1)

• Number Of Participants Reporting TEAEs And IARs

  Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-associated reactions (IARs). The number of participants who discontinued from the study due to a TEAE is also presented. An IAR was defined as any adverse event that occurred during the 2-hour infusion or within 4 hours after the end of the infusion and was assessed by the investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. TEAEs that occurred after the first dose administration at Week 1 through the End of Study (EOS) are presented. End of study was 30 days (+ 7 days) after the last dose of study drug (at Week 260).

  From after first dose administration post-Baseline through EOS during study LAL-CL04

Secondary Outcomes (7)

• Changes From Baseline In ALT And AST

  Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

• Changes From Baseline In Liver Volume

  Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

• Changes From Baseline In Liver Fat Content

  Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, and Week 260

• Changes From Baseline In GGT And ALP

  Baseline, Week 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

• Changes From Baseline In Serum Lipids

  Baseline, Week 10 or 12, Week 24, Week 52, Week 104, Week 156, Week 208, Week 260, and EOS

Study Arms (1)

Open-Label Sebelipase Alfa

EXPERIMENTAL

Participants were administered sebelipase alfa once weekly (qw) as an intravenous (IV) infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 milligrams per kilogram \[mg/kg\]) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing every other week (qow) at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years.

Drug: sebelipase alfa

Interventions

sebelipase alfa DRUG

Sebelipase alfa is a recombinant human lysosomal acid lipase.

Also known as: SBC-102, Kanuma®

Open-Label Sebelipase Alfa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant received all 4 scheduled doses of sebelipase alfa in Study LAL-CL01 with no life-threatening or unmanageable study drug toxicity.

You may not qualify if:

• Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances
• Clinically significant abnormal values on laboratory screening tests, other than LFTs or lipid panel tests

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (10)

Unknown Facility

Eureka, California, 95501-320, United States

Location

Unknown Facility

Sacramento, California, 95817, United States

Location

Unknown Facility

San Francisco, California, 94143, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55455, United States

Location

Unknown Facility

New York, New York, 10029, United States

Location

Unknown Facility

Greater Sudbury, Ontario, Canada

Location

Unknown Facility

Prague, Czechia

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Leeds, United Kingdom

Location

Unknown Facility

Salford, United Kingdom

Location

Related Publications (2)

• 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 RESULT

• Malinova V, Balwani M, Sharma R, Arnoux JB, Kane J, Whitley CB, Marulkar S, Abel F. Sebelipase alfa for lysosomal acid lipase deficiency: 5-year treatment experience from a phase 2 open-label extension study. Liver Int. 2020 Sep;40(9):2203-2214. doi: 10.1111/liv.14603. Epub 2020 Aug 9.

  PMID: 32657505 DERIVED

Related Links

• Alexion website

MeSH Terms

Conditions

Cholesterol Ester Storage Disease; Wolman Disease; Lysosomal Storage Diseases

Interventions

Sebelipase alfa

Condition Hierarchy (Ancestors)

Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Infant, Newborn, Diseases

Results Point of Contact

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

clinicaltrials@alexion.com

475-230-2596

Publication Agreements

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

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: November 26, 2011
• First Posted: December 8, 2011
• Study Start: December 12, 2011
• Primary Completion: June 21, 2017
• Study Completion: June 21, 2017
• Last Updated: July 20, 2018
• Results First Posted: May 9, 2016

Record last verified: 2018-06

Locations

US (5); FR (1); CZ (1); CA (1); GB (2)