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

NCT ID: NCT02112994

Last Updated: 2019-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-24
• Study Completion Date: 2017-12-28

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).

Conditions

Lysosomal Acid Lipase Deficiency

Study Design

• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sebelipase Alfa

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.

Group Type: EXPERIMENTAL

Sebelipase Alfa

Intervention Type: DRUG

IV infusion of sebelipase alfa

Interventions

Sebelipase Alfa

IV infusion of sebelipase alfa

Intervention Type: DRUG

Other Intervention Names

SBC-102

Eligibility Criteria

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

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.

• Minimum Eligible Age: 8 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Chicago, Illinois, United States

Shreveport, Louisiana, United States

Cincinnati, Ohio, United States

Westmead, , Australia

Brussels, , Belgium

São Paulo, , Brazil

Halifax, Nova Scotia, Canada

Zagreb, , Croatia

Copenhagen, , Denmark

Freiburg im Breisgau, , Germany

Padua, , Italy

Mexico City, , Mexico

Amsterdam, , Netherlands

Moscow, , Russia

A Coruña, , Spain

Barcelona, , Spain

Madrid, , Spain

Balcalı, , Turkey (Türkiye)

Birmingham, , United Kingdom

Countries

United States; Australia; Belgium; Brazil; Canada; Croatia; Denmark; Germany; Italy; Mexico; Netherlands; Russia; Spain; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35442238 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2011-004287-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LAL-CL06

Identifier Type: -

Identifier Source: org_study_id