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Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency

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ClinicalTrials.gov Identifier: NCT01307098
Recruitment Status : Completed
First Posted : March 2, 2011
Results First Posted : December 11, 2018
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
This was the first clinical study of SBC-102 (sebelipase alfa) for the treatment of Lysosomal Acid Lipase (LAL) Deficiency. It was an open-label dose escalation study in adult participants with liver dysfunction due to LAL Deficiency and was designed to examine 3 doses of sebelipase alfa. The targeted number for this study was 9 evaluable participants.

Condition or disease Intervention/treatment Phase
Cholesterol Ester Storage Disease(CESD) Lysosomal Acid Lipase Deficiency LAL-Deficiency Drug: Sebelipase alfa 0.35 mg/kg Drug: Sebelipase alfa 1 mg/kg Drug: Sebelipase alfa 3 mg/kg Phase 1 Phase 2

Detailed Description:

The study was composed of a screening period, a treatment period, and a post-treatment follow-up period (including an End of Study visit). Participants who successfully completed screening assessments to determine study eligibility were allocated to 3 sequential cohorts (0.35, 1, or 3 milligrams/kilogram [mg/kg]). Within each cohort, one participant was initially dosed and, if sebelipase alfa was deemed safe and well tolerated in this participant (based on at least 24 hours of monitoring), dosing was allowed to be initiated for the remaining participants in the cohort. Initiation of dosing in the next cohort occurred only after all participants in the preceding cohort had been monitored for at least 5 days after the second infusion, without any evidence of significant safety signals, and an independent Safety Committee had reviewed the cumulative safety data and provided their recommendation on the acceptability of beginning dosing in the next cohort.

Cholesteryl Ester Storage Disease (CESD) is the late onset phenotype for LAL Deficiency, a lysosomal storage disorder, which also has an early onset phenotype known as Wolman disease that primarily affects infants. CESD can present in childhood but often goes unrecognized until adulthood when the underlying pathology is advanced. Many of the signs and symptoms are common to participants with other liver conditions.

CESD is an autosomal recessive genetic condition and is characterized by hepatomegaly, persistently abnormal liver function tests and type II hyperlipidemia. Splenomegaly and evidence of mild hypersplenism may affect some participants. Untreated, CESD may lead to fibrosis, cirrhosis, liver failure and death.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Multicenter Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SBC-102 in Adult Participants With Liver Dysfunction Due to Lysosomal Acid Lipase Deficiency
Actual Study Start Date : April 25, 2011
Actual Primary Completion Date : January 6, 2012
Actual Study Completion Date : January 6, 2012


Arm Intervention/treatment
Experimental: Sebelipase alfa 0.35 mg/kg
Cohort 1: Participants were administered once weekly (qw) infusions of 0.35 mg/kg sebelipase alfa.
Drug: Sebelipase alfa 0.35 mg/kg
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Other Names:
  • Kanuma
  • SBC-102

Experimental: Sebelipase alfa 1 mg/kg
Cohort 2: Participants were administered qw infusions of 1 mg/kg sebelipase alfa.
Drug: Sebelipase alfa 1 mg/kg
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Other Names:
  • Kanuma
  • SBC-102

Experimental: Sebelipase alfa 3 mg/kg
Cohort 3: Participants were administered qw infusions of 3 mg/kg sebelipase alfa.
Drug: Sebelipase alfa 3 mg/kg
Sebelipase alfa is a recombinant human lysosomal acid lipase.
Other Names:
  • Kanuma
  • SBC-102




Primary Outcome Measures :
  1. Number Of Participants Reporting TEAEs And Infusion-Related Reactions (IRRs) [ Time Frame: Screening up to Day 52 ]
    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-related reactions (IRRs). The number of participants who discontinued from the study due to a TEAE is also presented. An IRR was defined as any adverse event that occurred between the start of the infusion and 4 hours after completion 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female participants ≥ 18 and ≤ 65 years of age
  • Documented decreased LAL activity
  • Evidence of liver involvement

Exclusion Criteria:

  • Clinically significant concurrent disease, serious inter-current illness, concomitant medications or other extenuating circumstances
  • Clinically significant abnormal values on laboratory screening tests, other than liver function or lipid panel tests
  • Aspartate aminotransferase and/or alanine aminotransferase persistently elevated > 3x upper limit of normal at screening
  • Previous hemopoietic bone marrow or liver transplant
  • Current history of alcohol abuse

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01307098


Locations
United States, California
Stanford, California, United States, 94305
United States, New York
New York, New York, United States, 10029
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15213
Czechia
Prague, Czechia, 12000
France
Paris, France, 75743
United Kingdom
Cambridge, United Kingdom, CB20QQ
Manchester, United Kingdom, M139WL
Sponsors and Collaborators
Alexion Pharmaceuticals

Additional Information:
Publications of Results:
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01307098     History of Changes
Other Study ID Numbers: LAL-CL01
First Posted: March 2, 2011    Key Record Dates
Results First Posted: December 11, 2018
Last Update Posted: December 11, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Alexion Pharmaceuticals:
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:
Wolman Disease
Cholesterol Ester Storage Disease
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Infant, Newborn, Diseases
Lipid Metabolism Disorders
Metabolic Diseases